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26 Jun 2019 at 01:33
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Bibliography on: Invasive Ductal Carcinoma (causes)


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RJR: Recommended Bibliography 26 Jun 2019 at 01:33 Created: 

Invasive Ductal Carcinoma (causes)

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

The causes of invasive ductal carcinoma have not been conclusively established. Researchers have determined that cancer can form when the cells in a milk-producing duct undergo changes that cause them to grow uncontrollably, divide very rapidly or remain viable longer than they should. The result is an accumulation of excess cells that can form a mass, or tumor, and potentially spread to nearby lymph nodes and distant areas of the body. The underlying reason for those cellular changes, however, remains unclear.

By evaluating the results of extensive studies, scientists have identified certain hormonal, environmental and lifestyle factors that are believed to influence a person's breast cancer risk, such as smoking, poor nutrition and prior radiation therapy administered to the chest area. Even so, it's important to keep in mind that some individuals who have no risk factors develop cancer, while others with one or more risk factors do not. Most likely, the precise cause is a complex interaction of many factors.

In rare cases, the causes of invasive ductal carcinoma have been traced to inherited attributes, such as mutations of the: (a) Breast cancer gene 1 (BRCA1), a tumor suppressor gene, (b) Breast cancer gene 2 (BRCA2), a tumor suppressor gene, or (c) ErbB2 gene, which produces the HER2 protein that promotes cellular proliferation.

Created with PubMed® Query: ("invasive ductal carcinoma" OR IDC) and (cause OR caused OR etiology) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-06-24
CmpDate: 2019-06-24

Jerevall PL, Brock J, Palazzo J, et al (2019)

Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.

Breast cancer research and treatment, 173(2):375-383.

PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients.

METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed.

RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk.

CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.

RevDate: 2019-06-24
CmpDate: 2019-06-24

Kizy S, Huang JL, Marmor S, et al (2018)

Distribution of 21-Gene Recurrence Scores Among Breast Cancer Histologic Subtypes.

Archives of pathology & laboratory medicine, 142(6):735-741.

CONTEXT: - The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain.

OBJECTIVE: - To determine the distribution of RS among various histologic subtypes using a population database.

DESIGN: - Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database. Recurrence scores were categorized into risk groups using both traditional and Trial Assigning Individualized Options for Treatment cutoffs. Multivariable logistic regression was used to determine factors associated with high-risk RS.

RESULTS: - We identified 45 618 patients with stage I to III, estrogen receptor-positive, HER2-negative breast cancer who had RS available. Overall, 3087 (7%) and 6337 (14%) of cancers were classified as high risk based on traditional and Trial Assigning Individualized Options for Treatment RS cutoffs, respectively. The proportion of high-risk RS ranged from 1% (tubular, 2 of 225) to 68% (medullary, 13 of 19) and 4% (tubular, 10 of 225) to 79% (medullary, 15 of 19) for traditional and Trial Assigning Individualized Options for Treatment cutoffs, respectively. Based on multivariable logistic regression (excluding medullary), subtypes other than invasive ductal carcinoma and papillary carcinoma were significantly associated with lower RS. The strongest predictors of a high-risk RS were higher tumor grade and negative progesterone receptor status.

CONCLUSIONS: - We identified distinct distributions of RS among different histologic subtypes of breast cancer. Excluding medullary carcinoma, histologic subtypes other than invasive ductal carcinoma and papillary carcinoma all predict lower RS.

RevDate: 2019-06-21
CmpDate: 2019-06-21

Bao Y, Wang L, Shi L, et al (2019)

Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.

Cellular & molecular biology letters, 24:38 pii:162.

Background: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.

Methods: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.

Results: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.

Conclusion: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.

RevDate: 2019-06-18
CmpDate: 2019-06-18

Myers MB, McKim KL, Banda M, et al (2019)

Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology.

International journal of molecular sciences, 20(5): pii:ijms20051011.

Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10-5, the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.

RevDate: 2019-06-18
CmpDate: 2019-06-18

Ng CS, Sinha A, Aniweh Y, et al (2018)

tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum.

Molecular systems biology, 14(10):e8009.

Among components of the translational machinery, ribonucleoside modifications on tRNAs are emerging as critical regulators of cell physiology and stress response. Here, we demonstrate highly coordinated behavior of the repertoire of tRNA modifications of Plasmodium falciparum throughout the intra-erythrocytic developmental cycle (IDC). We observed both a synchronized increase in 22 of 28 modifications from ring to trophozoite stage, consistent with tRNA maturation during translational up-regulation, and asynchronous changes in six modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed that up- and down-regulated proteins in late but not early stages have a marked codon bias that directly correlates with parallel changes in tRNA modifications and enhanced translational efficiency. We thus propose a model in which tRNA modifications modulate the abundance of stage-specific proteins by enhancing translation efficiency of codon-biased transcripts for critical genes. These findings reveal novel epitranscriptomic and translational control mechanisms in the development and pathogenesis of Plasmodium parasites.

RevDate: 2019-06-13
CmpDate: 2019-06-13

Yano Y, Kuga T, Harada T, et al (2018)

[A Case of Suspected Therapy-Related Leukemia after Chemotherapy for Breast Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 45(12):1775-1777.

Therapy-related leukemia(TRL)is a distinctive clinical syndrome that occurs after exposure to chemotherapy or radiotherapy. We report a case of suspected TRLafter chemotherapy in a patient with breast cancer. A 61-year-old woman underwent total mastectomy and sentinel lymph node biopsy(negative)for her breast cancer. Histopathologic analysis showed invasive ductal carcinoma, pStage I. Her subtype histology was Luminal B-type, and postoperative adjuvant chemotherapy and endocrine therapy were administered. Four years after chemotherapy, a blood examination showed pancytopenia. Bone marrow examination showed acute promyelocytic leukemia. She was treated with chemotherapy and achieved complete remission. Breast cancer provides long-term survival after treatment. Attention should be paid to the occurrence of TRLin breast cancer surveillance.

RevDate: 2019-06-13
CmpDate: 2019-06-13

Abdalla AS, Lazarevska A, Omer MM, et al (2018)

Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding During Chemotherapy: A Case Report and Literature Review.

Chirurgia (Bucharest, Romania : 1990), 113(4):564-570.

The most common sites of invasive breast cancer metastasis are the lungs, liver, bones and brain. Less frequent sites include the gastrointestinal tract, pancreas, spleen, thyroid, adrenals, kidneys, heart and female genital tract. The uterus is reported as a rare site for metastasis, and even more so for an isolated metastasis. Other sites of extra-genital sources for uterine metastases include the colon, stomach, pancreas, gallbladder, lung, cutaneous melanoma, urinary bladder and thyroid. The rarity of breast cancer metastasis to the uterine cervix could be explained by the fact that the cervix has a small blood supply and an afferent lymph drainage system alone. It is rare to diagnose a cervical metastasis prior to eliciting the primary breast disease. Invasive lobular carcinoma metastasises to the female reproductive system more frequently than invasive ductal carcinoma. This paper presents a case of breast cancer metastasis to the cervix.

RevDate: 2019-06-14
CmpDate: 2019-06-14

Cougoule C, Lastrucci C, Guiet R, et al (2018)

Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells.

Frontiers in immunology, 9:846.

Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo, or in collagen matrices in vitro. However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam3CSK4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mesenchymal mode in dense matrices, they formed 3D podosomes at the tip of cell protrusions. Using PGE2, known to disrupt podosomes in DC, we observed that the cells remained in an immature status and the mesenchymal migration mode was abolished. We also observed that, while CCL5 (attractant of iDC) enhanced both amoeboid and mesenchymal migration of iDC, CCL19 and CCL21 (attractants of mDC) only enhanced mDC-LPS amoeboid migration without triggering mesenchymal migration. Finally, we examined the migration of iDC in tumor cell spheroids, a tissue-like 3D environment. We observed that iDC infiltrated spheroids of tumor cells using both migration modes. Altogether, these results demonstrate that human DC adopt the mesenchymal mode to migrate in 3D dense environments, which relies on their capacity to form podosomes independent of their maturation status, paving the way of further investigations on in vivo DC migration in dense tissues and its regulation during infections.

RevDate: 2019-06-07

Hamzah JL, Ong KW, BY Tan (2019)

Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.

Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.

RevDate: 2019-06-11

Haythorne E, Rohm M, van de Bunt M, et al (2019)

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.

Nature communications, 10(1):2474 pii:10.1038/s41467-019-10189-x.

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.

RevDate: 2019-05-30

Zhu J, Sun K, Xu X, et al (2019)

A preliminary attempt of non-intervention in the treatment of patients with intervertebral disc calcification combined with ossification of the posterior longitudinal ligament.

World neurosurgery pii:S1878-8750(19)31446-9 [Epub ahead of print].

BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, contrary remains in terms of the best way to treat this condition.

CASE DESCRIPTION: An eight-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurological dysfunction. CT and MRI revealed the calcified intervertebral disc and OPLL at C5/6 level and the spinal cord compression. We performed a non-intervention strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and CT revealed the complete resorption of ossified lesion. MRI also showed no sign of compression on the spinal cord and nerve root at the involved segment.

CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and gender-specific, further research is necessary. Ladder therapy, as described in the text, may be an acceptable treatment for IDC combined with OPLL.

RevDate: 2019-05-23
CmpDate: 2019-05-23

Rusak A, Jablonska K, Piotrowska A, et al (2019)

Correlation of Expression of CHI3L1 and Nogo-A and their Role in Angiogenesis in Invasive Ductal Breast Carcinoma.

Anticancer research, 39(5):2341-2350.

BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC).

MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data.

RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found.

CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.

RevDate: 2019-05-15

Baydoun S, Gonzalez P, Whitman GJ, et al (2019)

Is Ductography Still Warranted in the 21st century?.

The breast journal [Epub ahead of print].

OBJECTIVE: To determine the utility of ductography in conjunction with mammography and ultrasound in patients with pathologic nipple discharge, and the incremental role of MRI after triple-modality evaluation.

MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had presented with pathologic nipple discharge and had undergone mammography and/or ultrasound and ductography between January 1, 2005, and October 31, 2010. We tested the diagnostic sensitivity, specificity and accuracy of combined triple-modality evaluation as well as of MRI performed in addition to these imaging techniques. We used the gold standard of image-guided biopsies, surgical excision, or long-term clinical and imaging follow-up.

RESULTS: Among 94 study patients, benign papillomas were identified in 42 (44.7%), abscess in one (1%), duct ectasia in four (4.3%), and malignancy (invasive ductal carcinoma or ductal carcinoma in situ) or high-risk lesion (atypical ductal hyperplasia) in 10 (10.6%). Forty-six patients (49%) underwent surgical excision; 89.1% of which had presurgical planning with ductography. In 35 (37.2%) with negative imaging, resolution of nipple discharge was confirmed on median clinical and imaging follow-up of 36 months. Two patients with negative imaging were lost to follow-up. Sensitivity, specificity, PPV, and NPV for accurately demonstrating the etiology of pathologic nipple discharge were 13%, 97%, 89%, and 37% respectively for mammography; 73%, 97%, 98%, and 64% respectively for ultrasound; 76%, 72%, 84%, and 61% respectively for ductography; 86%, 70%, 85%, and 72% respectively for combined ultrasound and ductography; and 75%, 100%, 100% and 67% respectively for DCE-MRI.

CONCLUSION: The combination of mammography, ultrasound and ductography is highly accurate for identifying the etiology of pathologic nipple discharge. DCE-MRI can be used as an alternate to ductography if necessary.

RevDate: 2019-05-09

Aplin FP, GY Fridman (2019)

Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.

Frontiers in neuroscience, 13:379.

Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.

RevDate: 2019-05-16

Sanderink WBG, Laarhuis BI, Strobbe LJA, et al (2019)

A systematic review on the use of the breast lesion excision system in breast disease.

Insights into imaging, 10(1):49 pii:10.1186/s13244-019-0737-3.

PURPOSE: To outline the current status of and provide insight into possible future research on the breast lesion excision system (BLES) as a diagnostic and therapeutic device.

METHODS: A systematic search of the literature was performed using PubMed, Embase, and the Cochrane databases to identify relevant studies published between January 2002 and April 2018. Studies were considered eligible for inclusion if they evaluated the diagnostic or therapeutic accuracy or safety of BLES.

RESULTS: Ultimately, 17 articles were included. The reported underestimation rates of atypical ductal hyperplasia and ductal carcinoma in situ (DCIS) ranged from 0 to 14.3% and from 0 to 22.2%, respectively. Complete excision rates for invasive ductal carcinoma and DCIS ranged from 5.3 to 76.3%. Bleeding was the most frequently reported complication (0-11.8%). Device-related complications may arise, with an empty basket being the most common (0.6-3.6%). Thermal damage of the specimen, caused by the use of a radiofrequency cutting wire, was reported in eight of the included studies. Most thermal artifacts were reported as superficial and small (0.1-1.9 mm).

CONCLUSIONS: The BLES, an automated, image-guided, single-pass biopsy system for breast lesions using radiofrequency is designed to excise and retrieve an intact tissue specimen. It is an efficient and safe breast biopsy method with acceptable complication rates, which may be used as an alternative to vacuum-assisted biopsies. The variable rate of complete excision raises questions about the possibility to use BLES as a therapeutic device for the excision of small lesions. Further research should focus on this aspect of BLES.

RevDate: 2019-06-10
CmpDate: 2019-05-28

Li JP, Zhang XM, Zhang Z, et al (2019)

Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.

Medicine, 98(18):e15449.

TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.

RevDate: 2019-05-03

Hinnen D, DF Kruger (2019)

Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials.

Diabetes, metabolic syndrome and obesity : targets and therapy, 12:447-455 pii:dmso-12-447.

Background: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases.

Purpose: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D.

Conclusion: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions.

RevDate: 2019-04-26

Albayrak M, Senol O, Demirkaya-Miloglu F, et al (2019)

Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.

Bratislavske lekarske listy, 120(3):184-187.

OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples.

METHODS: Samples were deparaffinized and 20‑micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model.

RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones.

CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).

RevDate: 2019-04-19
CmpDate: 2019-04-19

Leshem R, van Lieshout PHHM, Ben-David S, et al (2019)

Does emotion matter? The role of alexithymia in violent recidivism: A systematic literature review.

Criminal behaviour and mental health : CBMH, 29(2):94-110.

BACKGROUND: Several variables have been evidenced for their association with violent reoffending. Resultant interventions have been suggested, yet the rate of recidivism remains high. Alexithymia, characterised by deficits in emotion processing and verbal expression, might interact with these other risk factors to affect outcomes.

AIM: Our goal was to examine the role of alexithymia as a possible moderator of risk factors for violent offender recidivism. Our hypothesis was that, albeit with other risk factors, alexithymia increases the risk of violent reoffending.

METHOD: We conducted a systematic literature review, using terms for alexithymia and violent offending and their intersection.

RESULTS: (a) No study that directly tests the role of alexithymia in conjunction with other potential risk factors for recidivism and actual violent recidivism was uncovered. (b) Primarily alexithymia researchers and primarily researchers into violence have separately found several clinical features in common between aspects of alexithymia and violence, such as impulsivity (total n = 24 studies). (c) Other researchers have established a relationship between alexithymia and both dynamic and static risk factors for violent recidivism (n = 16 studies).

CONCLUSION: Alexithymia may be a possible moderator of risk of violent offence recidivism. Supplementing offenders' rehabilitation efforts with assessments of alexithymia may assist in designing individually tailored interventions to promote desistance among violent offenders.

RevDate: 2019-04-16

Rohm M, Zeigerer A, Machado J, et al (2019)

Energy metabolism in cachexia.

EMBO reports, 20(4):.

Cachexia is a wasting disorder that accompanies many chronic diseases including cancer and results from an imbalance of energy requirements and energy uptake. In cancer cachexia, tumor-secreted factors and/or tumor-host interactions cause this imbalance, leading to loss of adipose tissue and skeletal and cardiac muscle, which weakens the body. In this review, we discuss how energy enters the body and is utilized by the different organs, including the gut, liver, adipose tissue, and muscle, and how these organs contribute to the energy wasting observed in cachexia. We also discuss futile cycles both between the organs and within the cells, which are often used to fine-tune energy supply under physiologic conditions. Ultimately, understanding the complex interplay of pathologic energy-wasting circuits in cachexia can bring us closer to identifying effective treatment strategies for this devastating wasting disease.

RevDate: 2019-04-22
CmpDate: 2019-04-22

Tewari SG, Rajaram K, Schyman P, et al (2019)

Short-term metabolic adjustments in Plasmodium falciparum counter hypoxanthine deprivation at the expense of long-term viability.

Malaria journal, 18(1):86 pii:10.1186/s12936-019-2720-3.

BACKGROUND: The malarial parasite Plasmodium falciparum is an auxotroph for purines, which are required for nucleic acid synthesis during the intra-erythrocytic developmental cycle (IDC) of the parasite. The capabilities of the parasite and extent to which it can use compensatory mechanisms to adapt to purine deprivation were studied by examining changes in its metabolism under sub-optimal concentrations of hypoxanthine, the primary precursor utilized by the parasite for purine-based nucleic acid synthesis.

METHODS: The concentration of hypoxanthine that caused a moderate growth defect over the course of one IDC was determined. At this concentration of hypoxanthine (0.5 μM), transcriptomic and metabolomic data were collected during one IDC at multiple time points. These data were integrated with a metabolic network model of the parasite embedded in a red blood cell (RBC) to interpret the metabolic adaptation of P. falciparum to hypoxanthine deprivation.

RESULTS: At a hypoxanthine concentration of 0.5 μM, vacuole-like structures in the cytosol of many P. falciparum parasites were observed after the 24-h midpoint of the IDC. Parasites grown under these conditions experienced a slowdown in the progression of the IDC. After 72 h of deprivation, the parasite growth could not be recovered despite supplementation with 90 µM hypoxanthine. Simulations of P. falciparum metabolism suggested that alterations in ubiquinone, isoprenoid, shikimate, and mitochondrial metabolism occurred before the appearance of these vacuole-like structures. Alterations were found in metabolic reactions associated with fatty acid synthesis, the pentose phosphate pathway, methionine metabolism, and coenzyme A synthesis in the latter half of the IDC. Furthermore, gene set enrichment analysis revealed that P. falciparum activated genes associated with rosette formation, Maurer's cleft and protein export under two different nutrient-deprivation conditions (hypoxanthine and isoleucine).

CONCLUSIONS: The metabolic network analysis presented here suggests that P. falciparum invokes specific purine-recycling pathways to compensate for hypoxanthine deprivation and maintains a hypoxanthine pool for purine-based nucleic acid synthesis. However, this compensatory mechanism is not sufficient to maintain long-term viability of the parasite. Although P. falciparum can complete a full IDC in low hypoxanthine conditions, subsequent cycles are disrupted.

RevDate: 2019-05-28
CmpDate: 2019-05-28

Li Y, Zhang N, Zhang H, et al (2019)

Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma.

Journal of clinical pathology, 72(6):418-424.

AIMS: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors.

METHODS: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19 383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the χ2 test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot.

RESULTS: A total of 586 patients with TN-MBC and 18 797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS.

CONCLUSION: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer.

RevDate: 2019-03-07

Menichetti F, Bertolino G, Sozio E, et al (2018)

Impact of infectious diseases consultation as a part of an antifungal stewardship programme on candidemia outcome in an Italian tertiary-care, University hospital.

Journal of chemotherapy (Florence, Italy), 30(5):304-309.

Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.

RevDate: 2019-03-07

Goodfellow J, Gorrie G, Leach V, et al (2019)

Cancer and motor neuron disease-causal or coincidental? Two contrasting cases.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology pii:10.1007/s10072-019-03784-9 [Epub ahead of print].

INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission.

CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.

RevDate: 2019-04-01
CmpDate: 2019-03-26

Sawai H, Kurimoto M, Koide S, et al (2019)

Invasive Ductal Carcinoma Arising in Mucinous Cystic Neoplasm of Pancreas: A Case Report.

The American journal of case reports, 20:242-247 pii:914092.

BACKGROUND Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. CASE REPORT A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. CONCLUSIONS We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.

RevDate: 2019-02-21

Nguyen B, Veys I, Leduc S, et al (2019)

Genomic, transcriptomic, epigenetic, and immune profiling of mucinous breast cancer.

Journal of the National Cancer Institute pii:5355042 [Epub ahead of print].

While invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC patients are generally older and have an excellent prognosis while at the pathological level, these tumors present with cells floating in extracellular mucin. To unravel the molecular architecture of MuBC, we applied low pass whole genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes (TIL) to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Genomic data (n = 26 MuBC, n = 535 estrogen-receptor (ER) positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC) and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low TIL levels (median = 0.0%, average = 3.4%, 95% CI = 1.9-4.9%). Compared to IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test), and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs. 6.7% in MuBC, P = .01 in ICGC; and 34.8% vs 0.0%, P = .02 in TCGA, two-sided Fisher's exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC.

RevDate: 2019-05-22
CmpDate: 2019-05-22

Hybiak J, Domagala P, W Domagala (2018)

BRCA1 and PARP1 mRNA expression during progression from normal breast to ductal carcinoma in situ and invasive breast cancer: a laser microdissection study.

Polish journal of pathology : official journal of the Polish Society of Pathologists, 69(4):347-355.

The contribution of DNA damage repair mechanisms to the progression of normal breast to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma is largely unknown. The purpose of this report was to assess the mRNA expression levels of two important genes associated with DNA repair, BRCA1 and PARP1, in normal breast tissue, DCIS G1, G2 and G3, and co-existing adjacent invasive ductal carcinoma. BRCA1 and PARP1 mRNA expression was assessed in 32 ductal carcinomas in situ of the breast using a laser microdissection and pressure catapulting system and quantitative real-time PCR. The relative expression of BRCA1 mRNA was significantly increased in DCIS G2 and DCIS G3 relative to normal breast tissue (p = 0.02, p = 0.001, respectively). Significant differences in BRCA1 expression were observed between DCIS G1 and G2 (p = 0.02) and between DCIS G1 and G3 (p = 0.0007). No significant differences in BRCA1 expression were observed between normal breast tissue and DCIS G1 and between DCIS component and adjacent invasive ductal carcinoma. No significant differences in the relative expression of PARP1 mRNA were observed between groups. Increased BRCA1 mRNA expression (but not PARP1 mRNA) occurs early in the development of breast cancer, i.e. at the noninvasive (DCIS) stage, suggesting a demand for increased activity of a DNA double-strand break repair by homologous recombination. DCIS G1 and normal breast tissue share highly similar BRCA1 and PARP1 expression level. This finding supports the idea that DCIS G1 belongs to a separate family of precursor lesions with low malignant potential.

RevDate: 2019-03-10

Miyake M, Yamada A, Miyake K, et al (2019)

Esophageal metastasis of breast cancer during endocrine therapy for pleural dissemination 21 years after breast surgery: a case report.

Surgical case reports, 5(1):22 pii:10.1186/s40792-019-0585-x.

BACKGROUND: The esophageal metastasis of breast cancer is rare. Moreover, it is extremely unusual for patients to experience the symptoms of esophageal metastasis during their lifetimes. We present a case of dysphagia caused by esophageal metastasis after a long interval following a primary mastectomy.

CASE PRESENTATION: A 77-year-old woman with a history of heterochronous bilateral breast cancer and under treatment for pleural dissemination recurrence originating from right breast cancer complained of dysphagia. At the age of 56, she had undergone a right radical mastectomy for right breast cancer. The histopathological findings revealed invasive ductal carcinoma, pT3N1M0, which was estrogen receptor (ER)- and progesterone receptor (PgR)-positive. At the age of 73, she underwent a second operation, a left modified radical mastectomy. The histopathological examination revealed invasive ductal carcinoma, pT1N0M0, which was negative for ER, PgR, and human epidermal growth factor receptor 2 (HER2). Four years after completion of adjuvant therapy for the left breast cancer, pleural effusion on her left side was observed and histopathological examination of a sample revealed pleural dissemination resulting from the right breast cancer. After initiation of therapy for recurrence, she developed dysphagia and, therefore, underwent an upper gastrointestinal tract endoscopic examination. The examination revealed whole circumferential stenosis and a band unstained by Lugol's solution located 30 cm from her incisors. Examination of a biopsy specimen revealed a subepithelial luminal structure and dysplastic cells. Immunostaining was positive for CK7 and negative for CK20; furthermore, the sample was ER and PgR-positive. Considering the pathological findings, the patient was diagnosed with esophageal metastasis of her right breast cancer.

CONCLUSIONS: Metastatic lesions in the esophagus are often located in the submucosa; therefore, they may not be definitively diagnosed by histopathological examination of mucosal biopsy specimens. Esophageal metastasis originating from breast cancer often occurs as a part of multiple organ metastases; however, esophageal metastasis is usually not considered a prognostic factor for patients. Therefore, treatment should be determined according to the severity of the other metastatic sites and the degree of esophageal stenosis.

RevDate: 2019-05-06
CmpDate: 2019-05-06

Yan Z, Ohuchida K, Zheng B, et al (2019)

CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.

Journal of cancer research and clinical oncology, 145(5):1147-1164.

PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.

METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.

RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.

CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.

RevDate: 2019-04-18
CmpDate: 2019-04-18

Louarn N, Dauta A, Lechapt-Zalcman E, et al (2019)

Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap: A Case Resolved by 18F-DOPA PET/MRI.

Clinical nuclear medicine, 44(4):e315-e317.

A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.

RevDate: 2019-04-12
CmpDate: 2019-04-12

Kodera A, Inoue H, Ogura K, et al (2018)

[Bevacizumab plus Paclitaxel Therapy Was Effective for Metastatic Breast Cancer with Dysphagia Due to Mediastinal Lymph Node Metastasis-A Case Report].

Gan to kagaku ryoho. Cancer & chemotherapy, 45(13):2276-2278.

A 69-year-old woman noticed a tumor of the right breast, and presented to our hospital with dysphagia. A tumor of size 10 cm exposed to the skin and swollen axillary lymph node were observed. She was diagnosed with invasive ductal carcinoma, luminal-B by core-needle biopsy. CT scan revealed primary breast cancer with lung, bone, and lymph node metastasis. Endoscopic and fluoroscopic findings of the esophagus showed severe stenosis by extrinsic compression. In order to improve the quality of life(QOL)immediately, bevacizumab plus paclitaxel therapy was initiated. After the first course, the dysphagia improved, and she was able to take normal meals after 2 courses of treatment. Primary tumor and metastatic lesions had remarkably shrunk on CT scan. After 4 courses of treatment, we changed to endocrine therapy and continued outcome treatment. Bevacizumab was effective for immediate improvement of QOL in such as an oncologic emergent case of metastatic breast cancer.

RevDate: 2019-04-08

da Silva Filho AF, Vieira-de-Mello GS, Dos Santos PB, et al (2019)

N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.

Pathology oncology research : POR, 25(2):759-768.

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.

RevDate: 2019-01-27

Smalley T, Islam SMA, Apostolatos C, et al (2019)

Analysis of PKC-ζ protein levels in normal and malignant breast tissue subtypes.

Oncology letters, 17(2):1537-1546.

It is estimated that breast cancer will be the second leading cause of cancer-associated mortality in women in 2018. Previous research has demonstrated that the atypical protein kinase C-ζ (PKC-ζ) is a component of numerous dysregulated pathways in breast cancer, including cellular proliferation, survival, and cell cycle upregulation. The present study investigated the PKC-ζ protein in breast tissue to evaluate its potential as a biomarker for breast cancer invasion, and demonstrated that an overexpression of PKC-ζ protein can be indicative of carcinogenesis. The present study analyzed the expression of PKC-ζ in individuals with no tumor complications and malignant female human breast tissue samples (lobular carcinoma in situ, invasive lobular carcinoma, ductal carcinoma in situ and invasive ductal carcinoma) with the use of western blot analysis, immunohistochemistry and statistical analysis (83 samples). The present study also evaluated the invasive behavior of MDA-MB-231 breast cancer cells following the knockdown of PKC-ζ with a Transwell invasion assay and an immunofluorescent probe for filamentous actin (F-actin) organization. The data demonstrated that PKC-ζ expression was identified to be higher in invading tissues when compared with non-invading tissues. The results also suggest that PKC-ζ is more abundant in ductal tissues when compared with lobular tissues. In addition, the protein studies also suggest that PKC-ζ is a component for invasive behavior through the Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) pathway, and PKC-ζ is required for the F-actin reorganization in invasive cells. Therefore, PKC-ζ should be considered to be a biomarker in the development of breast cancer as well as an indicator of invading tumor cells.

RevDate: 2019-05-08
CmpDate: 2019-05-08

Liu Y, Ide Y, Inuzuka M, et al (2019)

BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.

Molecular genetics & genomic medicine, 7(3):e493.

BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations.

METHODS: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR).

RESULTS: (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023-0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR.

CONCLUSION: DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.

RevDate: 2019-04-15
CmpDate: 2019-04-15

Framarino-Dei-Malatesta M, Chiarito A, Bianciardi F, et al (2019)

Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.

BMC cancer, 19(1):36 pii:10.1186/s12885-018-5253-1.

BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer.

CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months.

CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.

RevDate: 2019-02-05
CmpDate: 2019-01-11

Bertozzi S, Cedolini C, Londero AP, et al (2019)

Sentinel lymph node biopsy in patients affected by breast ductal carcinoma in situ with and without microinvasion: Retrospective observational study.

Medicine, 98(1):e13831.

With the introduction of an organized mammographic screening, the incidence of ductal carcinoma in situ (DCIS) has experienced an important increase. Our experience with sentinel lymph node biopsy (SLNB) among patients with DCIS is reviewed.We collected retrospective data on patients operated on their breasts for DCIS (pTis), DCIS with microinvasion (DCISM) (pT1mi) and invasive ductal carcinoma (IDC) sized ≤2 cm (pT1) between January 2002 and June 2016, focusing on the result of SLNB.543 DCIS, 84 DCISM, and 2111 IDC were included. In cases of DCIS and DCISM, SLNB resulted micrometastatic respectively in 1.7% and 6.0% of cases and macrometastatic respectively in 0.9% and 3.6% of cases. 5-year disease-free survival and overall survival in DCISM and IDC were similar, while significantly longer in DCIS. 5-year local recurrence rate of DCIS and DCISM were respectively 2.5% and 7.9%, and their 5-year distant recurrence rate respectively 0% and 4%. IDC, tumor grading ≥2 and lymph node (LN) macrometastasis were significant predictors for decreased overall survival. Significant predictors for distant metastases were DCISM, IDC, macroscopic nodal metastasis, and tumor grading ≥2. Predictors for the microinvasive component in DCIS were tumor multifocality/multicentricity, grading ≥2, ITCs and micrometastases.Our study suggests that despite its rarity, sentinel node metastasis may also occur in case of DCIS, which in most cases are micrometastases. Even in the absence of an evident invasive component, microinvasion should always be suspected in these cases, and their management should be the same as for IDC.

RevDate: 2019-04-09
CmpDate: 2019-04-09

Wang G, Zhou C, Conklin C, et al (2019)

Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.

Virchows Archiv : an international journal of pathology, 474(3):333-339.

Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.

RevDate: 2019-03-27
CmpDate: 2019-03-27

Ssemmanda S, Katagirya E, Bukirwa P, et al (2018)

Breast diseases histologically diagnosed at a tertiary facility in Uganda (2005-2014).

BMC cancer, 18(1):1285 pii:10.1186/s12885-018-5208-6.

BACKGROUND: The prevalence and distribution of histologically diagnosed breast disease are not well documented in low income countries, Uganda inclusive. Although the greater majority of breast lesions globally are benign, breast cancer is the most frequently diagnosed cancer all over the world. We aimed at documenting the prevalence of different breast diseases histologically diagnosed at the histopathology laboratory of the Department of Pathology of the Makerere University College of Health Sciences (MakCHS Lab) over a decade (2005-2014). We also describe the demographic characteristics of the patients in Uganda diagnosed with breast disease at the MakCHS Lab during the same period.

METHODS: This was a 10 year retrospective study of histologically diagnosed breast disease between 2005 and 2014 inclusive at the MakCHS Lab. We extracted information from hard copies of all 2510 histopathology reports retrieved from archives of the Department of Pathology at the MakCHS Lab. 640 records that were either damaged beyond recognition of key details, were duplicated, were implausible or had no conclusive diagnosis made were excluded. Information to be analyzed was then entered into Epidata (version 3.1) on a password protected laptop. Data analysis was done using SPSS software (v16 for Windows × 64).

RESULTS: From the 1870 patients' records eventually analyzed, breast disease was most diagnosed in female patients (97.1%). The overall mean age for breast disease diagnosis was 33 years (S.D ± 16.46) and median age 26 years (IQR: 20-43). Fibroadenoma (40.1%) was the most diagnosed breast disease overall. We noticed steadily increasing frequency of diagnosis of cancerous breast diseases over the last half of the study period. Invasive ductal carcinoma was the most diagnosed breast cancer (326 cases, 55.6%). A high female to male breast cancer ratio of 48:1 was observed. The highest regional breast cancer proportion was from the Western region of the Country.

CONCLUSIONS: There is need for more research into the picture of breast disease in the country, covering various demographic characteristics of the country's population for all regions and informing about its incidence rates and prevalence and also the breast cancer risk estimate for benign breast disease.

RevDate: 2019-03-26
CmpDate: 2019-03-26

Semango GP, Charles RM, Swai CI, et al (2018)

Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.

BMC cancer, 18(1):1258 pii:10.1186/s12885-018-5155-2.

BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015.

METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values ≤10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value ≤5%. All patients' notes were kept confidential as per the Helsinki declaration.

RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/μl). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p < 0.009). Increased age, above 35 years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p < 0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p < 0.010).

CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.

RevDate: 2019-05-22
CmpDate: 2019-05-22

Dabarian AL, Mady C, Barbosa-Ferreira JM, et al (2019)

Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels.

Canadian journal of physiology and pharmacology, 97(2):140-145.

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 μU/mL) when compared with control (8.0 ± 4.9 μU/mL) and IDC (9.9 ± 5.0 μU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 μg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.

RevDate: 2019-05-23

Martínez Nicolás I, Lê Cook B, Flores M, et al (2019)

The impact of a comprehensive electronic patient portal on the health service use: an interrupted time-series analysis.

European journal of public health, 29(3):413-418.

BACKGROUND: There is little empirical research on the potential benefit that electronic patient portals (EPP) can have on the care quality and health outcomes of diverse multi-ethnic international populations. The purpose of this study is to determine the extent to which an EPP was associated with improvements in health service use.

METHODS: Using a quasi-experimental interrupted time-series approach, we assessed health service use before (April 2012-September 2015) and after (October 2015-December 2016) the implementation of a comprehensive EPP at four hospitals in Madrid, Spain. Primary outcomes were number of outpatient visits, any hospital admission, any 30-day all-cause readmission and any emergency department visit.

RESULTS: Implementation of the EPP was associated with a significant decline in readmissions. Among patients with chronic heart failure, EPP implementation was associated with a significant decline for all outcome measures, and among patients with COPD, a decline in all outcomes except readmissions. Among patients diagnosed with malignant hematological diseases, no significant changes were identified.

CONCLUSIONS: EPPs hold promise for reducing hospital readmissions. Certain patient populations with chronic conditions may differentially benefit from portal use depending on their needs for communication with their providers.

RevDate: 2019-01-11
CmpDate: 2019-01-11

Shettar A, Damineni S, Mukherjee G, et al (2018)

Gap junction β‑2 expression is negatively associated with the estrogen receptor status in breast cancer tissues and is a regulator of breast tumorigenesis.

Oncology reports, 40(6):3645-3653.

Gap junction β‑2 gene (GJB2, also known as connexin 26) is a member of the connexin family which forms gap junction channels. Many connexin genes have been considered to be tumor suppressor genes. However, the overexpression of GJB2 has been found to be associated with a poor prognosis in several human cancers. In our previous microarray study, we revealed the overexpression of GJB2 in breast cancer tissues. Hence, in this study, we investigated the expression of GJB2 in human breast cancer and its role in breast cancer cell proliferation and migration. The RT‑qPCR results revealed the upregulation of the GJB2 gene in invasive ductal carcinoma (P<0.001) of the breast. Immunohistochemical analysis revealed an intense cytoplasmic and membrane staining. We observed that the staining for GJB2 was more intense in the majority of the estrogen receptor (ER)‑negative breast cancer tissues compared to the normal breast tissues (P<0.0001). By contrast, the majority of the ER‑positive breast cancer samples exhibited weak to moderate staining; however, this difference was not statistically significant compared to the normal tisues. The knockdown of GJB2 in human breast cancer cell lines using shRNA led to a significant decrease in the proliferative ability and an increase in the migratory ability of breast cancer cells. In addition, the knockdown of GJB‑2 led to a significant reduction in tumor volume and proliferation (as demonstrated by MIB‑1 staining) in orthotopic xenografts in immunocompromised mice. On the whole, the findings of this study indicate that GJB2 may be an important regulator of breast tumorigenesis.

RevDate: 2019-05-20
CmpDate: 2019-05-20

Pusina S (2018)

Correlation of Serum Levels of Urokinase Activation Plasminogen (uPA) and Its Inhibitor (PAI-1) with Hormonal and HER-2 Status in the Early Invasive Breast Cancer.

Medical archives (Sarajevo, Bosnia and Herzegovina), 72(5):335-340.

Introduction: Breast cancer is the most common malignant tumor in women. On the list of causes of death immediately after lung cancer. It is a heterogeneous disease, considering the differences in morphological, cytogenetic, molecular, clinical and therapeutic aspects, so that the prognosis in a patient with the same histological grade and pathological status may vary.

Aim: In this paper we wanted to identify the correlation between the assay of the serum values of uPA-PAI-1 complexes and individual prognostic-predictive parameters, primarily with the status of estrogenic (Er), progesterogenic (PgR) and Her-2 receptors ("human epidermal growth factor).

Material and methods: The study was conducted at the Clinic for General and Abdominal Surgery, University Clinical Center of Sarajevo (CCUS), from September 2016 to April 2017. The study included 66 patients, ages 18 to 75, in whom by the needle biopsy preoperatively was pathohistologically verified primary invasive breast cancer.

Results: Two thirds of the sample were classified as invasive ductal carcinoma, similar to the percentage (68.2%) of pT2 size, and almost half in the grade G3. Lymph node status was negative in 54.5% of respondents, and positive in 31.8% of respondents. Most patients had positive estrogenic (83.3%) and progesterone receptors (62.1%). Almost 80% was Her-2 negative. The blood vessel invasion was present in 56.1%, while the neural invasion was present in less than a third of the sample (30.3%). Median values of uPA-PAI-1 complexes were 1.4 (interquartile range 0.9); almost 70% of the sample was negative for the status analysis of uPA-PAI-1 complex (<1).

Discussion: A statistically significant difference was determined in the mean values of uPA-PAI-1 complexes in subgroups according to menopausal status, tumor size, histological grade, histological type (invasive ductal carcinoma vs. invasive lobular cancer versus invasive ductal carcinoma vs. invasive lobular cancer), status axillary lymph nodes, Ki67 status (as binary variables), invasion of the blood vessels and neural invasion, as well as subgroups according to the status of expression of hormonal (estrogen and progesterone) receptors.

Conclusion: There is a statistically significant difference in the mean values of the uPA-PAI-1 complex and Her-2 receptor expression. Generally, in perspective, this would be the role played by the uPA/PAI-1 complex in breast cancer, which is that the elevated complex values have a negative prognosis and effect on survival, similar to the negative Her-2 receptor status. Complex uPA/PAI-1 is not a specific serum protein in breast cancer patients and cannot be taken as an individual prognostic-predictive marker for mass pre- or post treatment screening and prediction. Unfortunately, none of the biomarkers are able to independently and fully identify patients of the unknown stage of the disease with better or worse prognosis or to identify cases of more aggressive tumor behavior of the same stage for timely inclusion of adjuvant therapy and reduction of the risk of metastatic disease. The decision on treatment and prognosis should be the result of a combination of all diagnostic, therapeutic, pathohistological and molecular-genetic variables.

RevDate: 2019-06-10
CmpDate: 2019-04-29

Pearson SJ, Roy Sarkar T, McQueen CM, et al (2019)

ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.

Oncogene, 38(14):2611-2626.

There is increasing evidence that genomic instability is a prerequisite for cancer progression. Here we show that SIM2s, a member of the bHLH/PAS family of transcription factors, regulates DNA damage repair through enhancement of homologous recombination (HR), and prevents epithelial-mesenchymal transitions (EMT) in an Ataxia-telangiectasia mutated (ATM)-dependent manner. Mechanistically, we found that SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR. Once stabilized, SIM2s interacts with BRCA1 and supports RAD51 recruitment to the site of DNA damage. Loss of SIM2s through the introduction of shSIM2 or the mutation of SIM2s at one of the predicted ATM phosphorylation sites (S115) reduces HR efficiency through disruption of RAD51 recruitment, resulting in genomic instability and induction of EMT. The EMT induced by the mutation of S115 is characterized by a decrease in E-cadherin and an induction of the basal marker, K14, resulting in increased invasion and metastasis. Together, these results identify a novel player in the DNA damage repair pathway and provides a link in ductal carcinoma in situ progression to invasive ductal carcinoma through loss of SIM2s, increased genomic instability, EMT, and metastasis.

RevDate: 2019-03-25
CmpDate: 2019-03-25

Son K, Yu S, Shin W, et al (2018)

A Simple Guideline to Assess the Characteristics of RNA-Seq Data.

BioMed research international, 2018:2906292.

Next-generation sequencing (NGS) techniques have been used to generate various molecular maps including genomes, epigenomes, and transcriptomes. Transcriptomes from a given cell population can be profiled via RNA-seq. However, there is no simple way to assess the characteristics of RNA-seq data systematically. In this study, we provide a simple method that can intuitively evaluate RNA-seq data using two different principal component analysis (PCA) plots. The gene expression PCA plot provides insights into the association between samples, while the transcript integrity number (TIN) score plot provides a quality map of given RNA-seq data. With this approach, we found that RNA-seq datasets deposited in public repositories often contain a few low-quality RNA-seq data that can lead to misinterpretations. The effect of sampling errors for differentially expressed gene (DEG) analysis was evaluated with ten RNA-seq data from invasive ductal carcinoma tissues and three RNA-seq data from adjacent normal tissues taken from a Korean breast cancer patient. The evaluation demonstrated that sampling errors, which select samples that do not represent a given population, can lead to different interpretations when conducting the DEG analysis. Therefore, the proposed approach can be used to avoid sampling errors prior to RNA-seq data analysis.

RevDate: 2019-05-01

Schmidt SF, Rohm M, Herzig S, et al (2018)

Cancer Cachexia: More Than Skeletal Muscle Wasting.

Trends in cancer, 4(12):849-860.

Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.

RevDate: 2018-12-07
CmpDate: 2018-11-19

Lee SJ, Chung MS, Shin SJ, et al (2018)

Correlation of tumor uptake on breast-specific gamma imaging and fluorodeoxyglucose PET/CT with molecular subtypes of breast cancer.

Medicine, 97(43):e12840.

Mechanisms of technetium-99m sesta-methoxyisobutylisonitrile (sestamibi) and F-fluorodeoxyglucose (FDG) uptake by tumor are different. The purpose of this study was to investigate the association between the tumor uptake of these 2 tracers in invasive ductal carcinoma and to examine thecorrelation of uptake of each tracer with prognostic factors and tumor molecular subtypes.A total of 96 patients with invasive ductal carcinoma who underwent preoperative breast-specific gamma imaging and FDG positron-emission tomography/computed tomography were retrospectively enrolled. Tumor-to-background ratio (TBR) of sestamibi and maximum standardized uptake value (SUVmax) of FDG were correlated with each other. Each of them was then compared with prognostic factors and molecular subtypes.In all tumors, there was a moderate positive correlation between TBR and SUVmax (r = 0.520, P < .001). Both TBR and SUVmax were significantly correlated with tumor size, incidence of axillary lymph node metastasis, histologic grade, estrogen receptor, progesterone receptor status, and Ki-67.There is a moderate degree of association between TBR of sestamibi and SUVmax of FDG in the invasive breast cancer. Two imaging indexes showed the similar tendency related with prognostic factors and molecular subtypes. While both TBR and SUVmax were significantly different between luminal A and nonluminal A tumors, neither of them had high enough sensitivity or specificity to obviate pathologic and molecular diagnosis.

RevDate: 2019-02-15
CmpDate: 2019-02-11

Ye FG, Xia C, Ma D, et al (2018)

Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.

BMC cancer, 18(1):1085.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement.

METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software.

RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767).

CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.

RevDate: 2018-12-17
CmpDate: 2018-11-20

Liu A, Feng Y, Chen B, et al (2018)

A case report of metastatic breast cancer initially presenting with esophageal dysphagia.

Medicine, 97(45):e13184.

RATIONALE: Breast cancer metastasis to the esophagus is uncommon. To our knowledge, the present case is the first report of breast cancer with dysphagia as the initial symptom.

PATIENT CONCERNS: A 62-year-old woman was admitted to our hospital for progressive dysphagia.

DIAGNOSES: Endoscopic ultrasound-guided fine needle biopsy of the esophageal lesion found poorly differentiated carcinoma, and surgical resection of the breast nodule revealed invasive ductal carcinoma.

INTERVENTIONS: The patient underwent an esophagectomy, and the immunohistochemistry of surgical specimen was identified as metastatic breast cancer. Then patient was treated with chemotherapy and hormone therapy.

OUTCOMES: The patient remained symptom-free during 5 months of follow-up examinations.

LESSONS: This case indicates that metastatic breast cancer to the esophagus should be considered as a cause of esophageal stricture in older women.

RevDate: 2019-03-14
CmpDate: 2019-03-14

Golan Y, Alhadeff R, Glaser F, et al (2018)

Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.

PLoS computational biology, 14(11):e1006503.

Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2. Zinc is an essential trace element with 10% of the proteins in the human proteome capable of zinc binding. Thus, zinc deficiency or impairment of zinc homeostasis disrupt key cellular functions. Mammalian zinc transport proceeds via two transporter families: ZnT and ZIP; however, little is known about the zinc permeation pathway through these transporters. As a step towards this end, we herein undertook comprehensive computational analyses employing multiscale techniques, focusing on the human zinc transporter ZnT2 and its bacterial homologue, YiiP. Energy calculations revealed a favorable pathway for zinc translocation via alternating access. We then identified key residues presumably involved in the passage of zinc ions through ZnT2 and YiiP, and functionally validated their role in zinc transport using site-directed mutagenesis of ZnT2 residues. Finally, we use a CG Monte Carlo simulation approach to sample the transition between the inward-facing and the outward-facing states. We present our structural models of the inward- and outward-facing conformations of ZnT2 as a blueprint prototype of the transporter conformations, including the putative permeation pathway and participating residues. The insights gained from this study may facilitate the delineation of the pathways of other zinc transporters, laying the foundations for the molecular basis underlying ion permeation. This may possibly facilitate the development of therapeutic interventions in pathological states associated with zinc deficiency and other disorders based on loss-of-function mutations in solute carriers.

RevDate: 2019-04-04
CmpDate: 2019-04-04

Talei A, Tahmasebi S, Akrami M, et al (2018)

The Shiraz Breast Cancer Registry (SBCR): study design and primary reports.

Personalized medicine, 15(6):471-479.

AIM: This is a description of the largest breast cancer (BC) registry in Iran, termed the Shiraz Breast Cancer Registry (SBCR).

METHODS: Data on baseline and clinical characteristics, socioeconomic status, imaging, physical examination, histopathology, treatment and prognosis have been recorded for each individual.

RESULTS: Overall, 5937 were included in the report. Mean age of first presentation was 49.05 ± 11.69 years. Mean tumor size was 2.78 ± 1.76 cm. Most patients had stage 2 (46.9%) and 3 (25.5%) BCs, respectively. Most common type of BC was invasive ductal carcinoma (83.3%), followed by medullary carcinoma (3.8%). Overall, 12.9% were triple negative (HER2-, ER- and PR-).

CONCLUSION: The study provides an overview on the status of BC's in Iran and a wide opportunity for future studies.

RevDate: 2019-03-05
CmpDate: 2019-03-05

Drucis K, Brzeziński M, K Gniadek (2018)

[Synchronous gastrointestinal stromal tumor of stomach and invasive ductal carcinoma of both breasts].

Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 45(268):161-163.

Gastrointestinal stromal tumor (GIST), despite the fact that it accounts for less than 5% of all sarcomas, is the most common mesenchymal tumor of the alimentary canal. Synchronous and metachronous stromal tumors are very rare findings. Only a few such cases can be found in the literature, and yet most of them is connected with Von Recklinghausen's disease or Carney's triad in which it is proved a much higher frequency of occurrence of this kind of tumors.

CASE REPORT: We present a case of 64 years old women, who was diagnosed with invasive ductal carcinoma of both breast due to screening mammography. Patent was qualified to bilateral mastectomy. Perioperative computer tomography scan revealed an additional pathological abnormality situated beyond stomach light, which after resection and immunohistochemistry was found to be a gastrointestinal stromal tumor. This case emphasize the problem of synchronous stromal tumors, the detection of which is often difficult due to nonspecific symptoms. Despite the fact that the most common localization of coexisting tumors is the digestive tract, one should remember about the possibility of occurrence in less frequent locations such as the breast.

RevDate: 2019-02-15
CmpDate: 2019-02-05

Abood RA (2018)

Breast Cancer in Basra Oncology Center: A Clinico- Epidemiological Analysis.

Asian Pacific journal of cancer prevention : APJCP, 19(10):2943-2946.

RevDate: 2019-04-04
CmpDate: 2019-04-04

Dhage S, Ernlund A, Ruggles K, et al (2018)

A genomic ruler to assess oncogenic transition between breast tumor and stroma.

PloS one, 13(10):e0205602.

BACKGROUND: Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary. We therefore investigated the extent to which breast tumors alter stromal gene expression in three dimensions in women undergoing mastectomy with the intent of providing a genomic determination for development of future risk of recurrence criteria, and to inform the need for adjuvant full-breast irradiation.

METHODS AND FINDINGS: Genome-wide gene expression changes were determined in histopathologically normal breast tissue in 33 women undergoing mastectomy for stage II and III primary invasive ductal carcinoma at serial distances in three dimensions from the tumor. Gene expression was determined by genome-wide mRNA analysis and subjected to metagene mRNA characterization. Tumor-like gene expression signatures in stroma were identified that surprisingly transitioned to a plastic, normalizing homeostatic signature with distance from tumor. Stroma closest to tumor displayed a pronounced tumor-like signature enriched in cancer-promoting pathways involved in disruption of basement membrane, cell migration and invasion, WNT signaling and angiogenesis. By 2 cm from tumor in all dimensions, stromal tissues were in transition, displaying homeostatic and tumor suppressing gene activity, while also expressing cancer supporting pathways.

CONCLUSIONS: The dynamics of gene expression in the post-tumor breast stroma likely co-determines disease outcome: reversion to normality or transition to transformation in morphologically normal tissue. Our stromal genomic signature may be important for personalizing surgical and adjuvant therapeutic decisions and risk of recurrence.

RevDate: 2019-02-15
CmpDate: 2019-02-05

Jafarian AH, Tasbandi A, Gilan H, et al (2018)

Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.

Indian journal of pathology & microbiology, 61(4):500-504.

Background: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors.

Materials and Methods: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels.

Results: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes.

Conclusion: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.

RevDate: 2019-01-02
CmpDate: 2019-01-02

Gaowa S, Futamura M, Tsuneki M, et al (2018)

Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor suppressor in human breast cancer.

Cancer science, 109(12):3910-3920.

Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA; P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in 6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%). Interestingly, all tumors derived from the 12 patients with Mieap promoter methylation or p53 mutations pathologically exhibited more aggressive and malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway resulted in significantly shorter disease-free survival (DFS) (P = 0.021), although p53 status is more prognostic in DFS than Mieap promoter methylation. These results indicate that p53/Mieap-regulated MQC has a critical role in tumor suppression in breast cancer, possibly in part through mitochondrial apoptotic pathway.

RevDate: 2019-06-09

Schumacher D, Morgenstern J, Oguchi Y, et al (2018)

Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes.

Molecular metabolism, 18:143-152.

OBJECTIVES: The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown.

METHODS: CRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1-/-) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions.

RESULTS: Glo1-/- mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1-/- mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes.

CONCLUSIONS: These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.

RevDate: 2019-01-28
CmpDate: 2019-01-28

Fortis SP, Vaxevanis CK, Mahaira LG, et al (2019)

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics.

Cancer immunology, immunotherapy : CII, 68(1):57-70.

Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy. These miRNAs, known to be involved in both tumor cell progression and immune pathways regulation, were analyzed in relation to circulating cytokines, tumor immune-cell infiltration and established prognostic clinicopathological characteristics. We have identified three different clusters, with overall low (C1), moderate (C2) or high (C3) expression levels of these six circulating miRNAs, which define three distinct groups of non-metastatic BCa patients characterized by different clinicopathological and immune-related characteristics, with possibly different clinical outcomes. Our data provide the proof-of-principle to support the notion that, up- or down-regulation of the same circulating miRNA may reflect different prognosis in BCa. Nonetheless, the prognostic and/or predictive potential of these three "signatures" needs to be further evaluated in larger cohorts of BCa patients with an, at least, 5-year clinical follow-up.

RevDate: 2018-12-21
CmpDate: 2018-12-21

Cai M, Feng G, G Zhang (2018)

A Case of Radioactivity Concentrated in Orbital Implant in 99mTc-MDP Bone Scan and SPECT/CT.

Clinical nuclear medicine, 43(12):e453-e454.

A 27-year-old woman, who has received a hydroxyapatite orbital implant in the right eye due to a trauma 6 years ago, was newly diagnosis with left breast invasive ductal carcinoma. Tc-MDP bone scan showed an increased radiotracer accumulation in the right orbit and SPECT/CT confirmed the focal accumulation at the site of the implant, without any sign of local malignant lesions or orbital infection. Radionuclide imaging could provide certain useful information in diagnosing or differential diagnosing orbital disease.

RevDate: 2018-11-14
CmpDate: 2018-11-05

Jouali F, Marchoudi N, Talbi S, et al (2018)

Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.

BMC cancer, 18(1):900.

BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.

METHODS: We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.

RESULTS: All patients were female with a median age of 46 years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.

CONCLUSION: The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.

RevDate: 2018-12-11
CmpDate: 2018-12-11

Du JJ, Chen YF, Peng Y, et al (2018)

Calcification of the intervertebral disc and ossification of posterior longitudinal ligament in children.

BMC musculoskeletal disorders, 19(1):316.

BACKGROUND: IDC in children, first reported by Baron in 1924, is very rare. OPLL of the cervical spine mainly affect people ages 50-70 years. The coexistence of IDC and OPLL in children is very rare, only six cases with 3 to 24 months' follow-up were reported to date.

CASE PRESENTATION: A 6-year-old boy presented with complains of neck pain at July 2007. The boy was treated by conservative treatment and observed up for 9 years. Neck pain greatly improved after a one-month conservative treatment and never recur. Laboratory tests revealed elevated ESR and CRP at admission and found nothing abnormal at 19-month and 9-year follow-up. Computed tomography and magnetic resonance imaging revealed IDC at C2/3, C3/4 and OPLL at C3/4 at admission and found minor calcification at C2/3 remained but calcification at C3/4 and OPLL at C3/4 completely disappeared at 19-month and 9-year follow-up. Nineteen months after initial diagnosis, restoration of T2-weighted signal intensity of C2/3 and C3/4 discs was observed through MRI. Loss of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal intensity of C3/4 disc was observed at 9-year follow-up.

CONCLUSIONS: IDC with OPLL in children is very rare. Conservative treatments are recommended with affirmative short-term and long-term clinical effects. More intensive observation with long-term follow-ups may be needed to warrant the clinical effects.

RevDate: 2019-05-08
CmpDate: 2019-05-08

Yirmiya K, Djalovski A, Motsan S, et al (2018)

Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth.

Psychoneuroendocrinology, 98:153-160.

The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-exposed children and their mothers, compared to matched controls, were followed from infancy and the current study reports findings from early adolescence (mean age = 11.66, SD = 1.23; N = 111; exposed = 58 control = 53). Youth and mothers' salivary cortisol (CT) and secretory immunoglobulin (s-IgA) levels were measured three times during a 4-hour lab visit, mother-child interaction patterns were quantified from a joint task, and children's anxiety symptoms diagnosed. Trauma-exposed children had higher levels of CT and s-IgA, exhibited more anxiety symptoms, and showed lower social collaboration with mother during the joint task. Trauma-exposed mothers had higher CT and s-IgA levels and showed less supportive parenting during mother-child interaction. Structural equation modeling defined three bio-behavioral paths by which trauma increases anxiety in youth. While the first path charted a behavioral link from exposure to child anxiety via diminished maternal support, the other two paths described mediated biological paths, one through HPA-axis functioning, the other via the immune system. Paths via the child's HPA and immune system were mediated by the parallel maternal variable. Findings are the first to describe the complex bio-behavioral interplay of stress and immune biomarkers and parenting behavior in shaping to the development of risk and resilience trajectories in youth growing up amidst chronic trauma.

RevDate: 2018-11-27
CmpDate: 2018-11-27

Shah S, Brock EJ, Jackson RM, et al (2018)

Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation.

Neoplasia (New York, N.Y.), 20(9):951-963.

Diagnosis of breast ductal carcinoma in situ (DCIS) presents a challenge since we cannot yet distinguish those cases that would remain indolent and not require aggressive treatment from cases that may progress to invasive ductal cancer (IDC). The purpose of this study is to determine the role of Rap1Gap, a GTPase activating protein, in the progression from DCIS to IDC. Immunohistochemistry (IHC) analysis of samples from breast cancer patients shows an increase in Rap1Gap expression in DCIS compared to normal breast tissue and IDCs. In order to study the mechanisms of malignant progression, we employed an in vitro three-dimensional (3D) model that more accurately recapitulates both structural and functional cues of breast tissue. Immunoblotting results show that Rap1Gap levels in MCF10.Ca1D cells (a model of invasive carcinoma) are reduced compared to those in MCF10.DCIS (a model of DCIS). Retroviral silencing of Rap1Gap in MCF10.DCIS cells activated extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK), induced extensive cytoskeletal reorganization and acquisition of mesenchymal phenotype, and enhanced invasion. Enforced reexpression of Rap1Gap in MCF10.DCIS-Rap1GapshRNA cells reduced Rap1 activity and reversed the mesenchymal phenotype. Similarly, introduction of dominant negative Rap1A mutant (Rap1A-N17) in DCIS-Rap1Gap shRNA cells caused a reversion to nonmalignant phenotype. Conversely, expression of constitutively active Rap1A mutant (Rap1A-V12) in noninvasive MCF10.DCIS cells led to phenotypic changes that were reminiscent of Rap1Gap knockdown. Thus, reduction of Rap1Gap in DCIS is a potential switch for progression to an invasive phenotype. The Graphical Abstract summarizes these findings.

RevDate: 2019-04-01
CmpDate: 2019-04-01

Clement Z, McLeay W, Hoffmann C, et al (2018)

Role of radiotherapy in women over the age of 65 after breast conserving surgery for breast cancer: A 5-year retrospective study.

Breast disease, 37(4):197-205.

BACKGROUND/OBJECTIVE: This study aimed to analyse the local recurrence (LR) and breast cancer related mortality (BCRM) in older women who underwent breast-conserving surgery (BCS) with and without adjuvant radiotherapy (XRT).

METHODS: This retrospective study included a total of 299 women who underwent BCS for early breast carcinoma, between the years of 2007 and 2011. Predictive risk factors, local recurrence (LR) and breast cancer related mortality (BCRM) were assessed with a mean follow-up period of 84 months.

RESULTS: Women over the age of 65 in the XRT and No-XRT groups showed similar incidence of LR (5.8% vs 5%, p = 0.838). Women over 65 years old with XRT had a higher rate of BCRM (5.8% vs 0%, p = 0.05). Resection margins >5 mm had a lower rate of BCRM (HR 0.395, p = 0.05). Women under the age of 65, invasive ductal carcinoma, grade-3 tumours, HER-2 positive, triple negative, lympho-vascular invasion, axillary lymph node positivity, high breast density on mammography were associated with increased risk of LR and BCRM.

CONCLUSIONS: XRT in women over the age of 65 did not decrease the risk of LR. Adjuvant XRT in older women should be offered to selective patients with high risk patient and tumour factors.

RevDate: 2018-11-14

Yan L, Dong X, Xu H, et al (2018)

Paraneoplastic cerebellar degeneration associated with breast cancer: A case report and review of the literature.

Molecular and clinical oncology, 9(2):163-167.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication of cancer characterized by rapid development of cerebellar ataxia. We herein present a case of a 67-year-old female patient with PCD caused by breast cancer. The patient presented with progressively worsening cerebellar deficits that had been misdiagnosed for several months prior to the identification of the anti-Yo autoantibodies in the serum. A whole-body positron emission tomography/computed tomography scan revealed a lesion in the lower outer quadrant of the left breast with slightly increased metabolism. On mammography, a lobulated high-density mass was identified in the left breast. The patient underwent left breast lumpectomy and the histological examination confirmed the presence of an invasive ductal carcinoma. After breast surgery, the patient exhibited marked neurological improvement at the 12-month follow-up. Therefore, it is crucial that clinicians include paraneoplastic neurological syndromes in the differential diagnosis of neurological disorders. The detection of characterized onconeural antibodies in the serum or cerebrospinal fluid may provide guidance in the search for an underlying tumor.

RevDate: 2018-12-27
CmpDate: 2018-12-27

Hashemi-Sadraei N, Müller-Greven GM, Abdul-Karim FW, et al (2018)

Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.

Journal of neuro-oncology, 140(2):237-248.

BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer.

METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining.

RESULTS: LC3-puncta+ tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta+ tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta+ tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival.

CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.

RevDate: 2019-01-18
CmpDate: 2019-01-18

Tadros AB, Wen HY, M Morrow (2018)

Breast Cancers of Special Histologic Subtypes Are Biologically Diverse.

Annals of surgical oncology, 25(11):3158-3164.

BACKGROUND/OBJECTIVE: Cancers classified as "special histologic subtypes" are felt to have a good prognosis. We used the 21-gene Oncotype DX Breast Recurrence Score® multigene assay to examine prognostic variation within special histologic subtypes. We also examined the Recurrence Score® (RS) distribution among the more common ductal (IDC) and lobular (ILC) cancers.

METHODS: 610,350 tumor specimens examined in the Genomic Health clinical laboratory from 2/2004 to 8/2017 were included. Specimen histology was classified centrally using a single H&E slide and World Health Organization criteria. RS distribution (low < 18, intermediate 18-30, and high ≥ 31) was compared among histologic subtypes.

RESULTS: Median patient age was 60 years (IQR 51-67); 80% were node negative. Most patients had low RS results (59.2%); only 9.5% had high results. The lowest mean RS was seen in the papillary subtype (11); the highest in the IDC group (18.4). Mean RS for all special subtypes was lower than that of IDC patients. When the high RS threshold was decreased from 31 to 25, as used in the TAILORx and RxPONDER trials, the number of high RS-result patients increased from 9.5% to 16.8%. Patients with ILC had a lower mean RS result than patients with IDC, 16.5 versus 18.4.

CONCLUSION: There is substantial diversity in predicted prognosis among patients with cancers classified as special histologic subtypes, with 12-25% having intermediate RS results and 0.5-9% having high RS results. Pending further definition of the role of chemotherapy for patients with intermediate RS results by TAILORx and RxPONDER, the RS result may help to inform systemic therapy decisions in these patients.

RevDate: 2018-11-26
CmpDate: 2018-11-26

Deipolyi AR, Riedl CC, Bromberg J, et al (2018)

Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.

Journal of vascular and interventional radiology : JVIR, 29(9):1226-1235.

PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes.

MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.8) between January 2011 and September 2017 after receiving ≥ 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization.

RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P = .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a response (P = .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P = .50).

CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.

RevDate: 2019-01-31
CmpDate: 2019-01-31

Hong JH, Ko YH, K Kang (2018)

RNA variant identification discrepancy among splice-aware alignment algorithms.

PloS one, 13(8):e0201822.

Next-generation sequencing (NGS) techniques have been generating various molecular maps, including transcriptomes via RNA-seq. Although the primary purpose of RNA-seq is to quantify the expression level of known genes, RNA variants are also identifiable. However, care must be taken to account for RNA's dynamic nature. In this study, we evaluated the following popular splice-aware alignment algorithms in the context of RNA variant-calling analysis: HISAT2, STAR, STAR (two-pass mode), Subread, and Subjunc. For this, we performed RNA-seq with ten pieces of invasive ductal carcinoma from breast tissue and three pieces of adjacent normal tissue from a single patient. These RNA-seq data were used to evaluate the performance of splice-aware aligners. Surprisingly, the number of common potential RNA editing sites (pRESs) identified by all alignment algorithms was less than 2% of the total. The main cause of this difference was the mapped reads on the splice junctions. In addition, the RNA quality significantly affected the outcome. Therefore, researchers must consider these experimental and bioinformatic features during RNA variant analysis. Further investigations of common pRESs discovered that BDH1, CCDC137, and TBC1D10A transcripts contained a single non-synonymous RNA variant that was unique to breast cancer tissue compared to adjacent normal tissue; thus, further clinical validation is required.

RevDate: 2018-11-14
CmpDate: 2018-11-08

Zhu X, Zeng Z, Qiu D, et al (2018)

Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c‑Fos and ATP6V0D2.

International journal of molecular medicine, 42(4):2071-2079.

Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether Vγ9Vδ2 T (γδ T) cells stimulate or inhibit iDC transdifferentiation into OCs has never been reported. The aim of the present study was to investigate the effects of γδ T cells on this transdifferentiation process. γδ T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co‑cultured with Transwelll inserts, with γδ T cells in the upper chamber and iDCs in the lower chamber. IDCs were treated with macrophage‑colony stimulating factor and receptor activator of nuclear factor‑κB (RANK) ligand. Tartrate resistant acid phosphatase (TRAP) assay and dentine resorption assay were performed to detect OC formation and their resorption capacity, respectively. The mRNA expression of OCs was examined using a microarray and real time‑quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that γδ T cells significantly inhibited the generation of the TRAP‑positive OCs from iDCs and their resorption capacity. The microarray analysis identified decreased expression level of Fos proto‑oncogene AP‑1 transcription factor subunit (c‑Fos), ATPase H+ transporting V0 subunit d (ATP6V0D2) and cathepsin K when iDCs were co‑cultured with γδ T cells. These genes are associated with OC differentiation, indicating that γδ T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/c‑Fos/ATP6V0D2 signaling pathway. The present findings provide novel insights into the interactions between human γδ T cells and iDCs, and demonstrate that γδ T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation.

RevDate: 2018-10-24
CmpDate: 2018-10-24

Papadopoulos EI, Papachristopoulou G, Ardavanis A, et al (2018)

A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance.

Clinical biochemistry, 60:24-32.

OBJECTIVE: MicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors.

METHODS: The expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients.

RESULTS: Our data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P = 0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P = 0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P = 0.026) and 0.663 (P = 0.001), respectively. Furthermore, miR-331 levels were elevated (P = 0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients.

CONCLUSIONS: Our results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.

RevDate: 2018-11-27
CmpDate: 2018-11-27

Lateef F, Jamal S, S Nasir (2018)

Her-2/neu Oncogene Amplification by Fluorescence In Situ Hybridization and Protein Overexpression on Immunohistochemistry in Breast Cancer.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 28(8):581-585.

OBJECTIVE: To investigate the concordance and discordance between the test results of Her-2/neu by immunohisto-chemistry (IHC) and flourescence In Situ hybridization (FISH) in breast cancer cases.

STUDY DESIGN: Descriptive cross-sectional study.

PLACE AND DURATION OF STUDY: Department of Histopathology, Dr. Ziauddin Hospital, Karachi, from 2011 to 2016.

METHODOLOGY: Forty-three specimens of invasive ductal carcinoma of breast were evaluated for grade and Her-2/neu status using IHC and FISH methods. Concordance and discordance between their results was determined.

RESULTS: There is 100% concordance between FISH and IHC in cases scoring 0, 1+ (negative) and 3+ (positive) immunostaining. Tumour cases scoring 2+ immunostaining showed amplification in 69.2% cases. All grade-I tumours were non-amplified on FISH, while most of the grade-III tumours showed Her-2/neu amplification on FISH. There is significant association of Her-2/neu IHC with tumour grade and FISH (p<0.05). A fairly high proportion i.e. 69.7% of cases showed Her-2/neu gene amplification. There was high concordance between Her-2/neu testing on IHC and FISH, (Kappa co-efficient 0.466, p <0.001).

CONCLUSION: Her-2/neu amplification increases with increasing grade of breast cancer. A high proportion of Her-2/neu gene amplified cases indicates aggressive disease in that area and need for FISH testing on large scale, which is the gold standard for equivocal cases on immunohistochemistry.

RevDate: 2018-11-15
CmpDate: 2018-11-15

Solanki R, Agrawal N, Ansari M, et al (2018)

COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters.

Asian Pacific journal of cancer prevention : APJCP, 19(7):1971-1975.

RevDate: 2018-11-14

Bai G, Jenkins S, Yuan W, et al (2018)

Field-Based Scoring of Soybean Iron Deficiency Chlorosis Using RGB Imaging and Statistical Learning.

Frontiers in plant science, 9:1002.

Iron deficiency chlorosis (IDC) is an abiotic stress in soybean that can cause significant biomass and yield reduction. IDC is characterized by stunted growth and yellowing and interveinal chlorosis of early trifoliate leaves. Scoring IDC severity in the field is conventionally done by visual assessment. The goal of this study was to investigate the usefulness of Red Green Blue (RGB) images of soybean plots captured under the field condition for IDC scoring. A total of 64 soybean lines with four replicates were planted in 6 fields over 2 years. Visual scoring (referred to as Field Score, or FS) was conducted at V3-V4 growth stage; and concurrently RGB images of the field plots were recorded with a high-throughput field phenotyping platform. A second set of IDC scores was done on the plot images (displayed on a computer screen) consistently by one person in the office (referred to as Office Score, or OS). Plot images were then processed to remove weeds and extract six color features, which were used to train computer-based IDC scoring models (referred to as Computer Score, or CS) using linear discriminant analysis (LDA) and support vector machine (SVM). The results showed that, in the fields where severe IDC symptoms were present, FS and OS were strongly positively correlated with each other, and both of them were strongly negatively correlated with yield. CS could satisfactorily predict IDC scores when evaluated using FS and OS as the reference (overall classification accuracy > 81%). SVM models appeared to outperform LDA models; and the SVM model trained to predict IDC OS gave the highest prediction accuracy. It was anticipated that coupling RGB imaging from the high-throughput field phenotyping platform with real-time image processing and IDC CS models would lead to a more rapid, cost-effective, and objective scoring pipeline for soybean IDC field screening and breeding.

RevDate: 2018-11-08
CmpDate: 2018-11-08

Gabanti E, Lilleri D, Scaramuzzi L, et al (2018)

Comparison of the T-cell response to human cytomegalovirus (HCMV) as detected by cytokine flow cytometry and QuantiFERON-CMV assay in HCMV-seropositive kidney transplant recipients.

The new microbiologica, 41(3):195-202.

Human cytomegalovirus (HCMV)-specific T-cell response in kidney transplant recipients (KTR) helps to identify patients at risk for severe infection. To assess the T-cell response, this study compared our in-house developed reference test, based on T-cell (both CD4+ and CD8+) stimulation by autologous HCMV-infected dendritic cells (iDC) and subsequent detection by cytokine flow cytometry (CFC-iDC), with the Quanti-FERON-CMV (QF-CMV) assay. Fifty-three HCMV-seropositive KTR were enrolled. At the DNAemia peak, 33 (62%) had low viral load (LVL, <3x105 DNA copies/mL) self-resolving infection, 19 (36%) high viral load (HVL, >3x105 DNA copies/mL) infection treated with antivirals, and one LVL patient (2%) tissue-invasive disease alone. Both assays showed a delayed recovery of HCMV-specific T-cell immunity in HVL vs LVL patients. Immune reconstitution kinetics did not significantly differ between the two assays in HVL patients. QF-CMV and CFC-iDC showed comparable sensitivities, but QF-CMV had a lower (although not significantly) specificity. Indeed, 7/19 HVL patients (37%) were erroneously considered protected from severe infection by QF-CMV, whereas CFC-iDC misidentified only 3/19 (16%) patients as protected. Although our reference test takes longer to complete, it appears slightly better at predicting patients at risk for severe HCMV infection. Moreover, QF-CMV may provide false negative results with some HLA types.

RevDate: 2019-01-23

Brunstein Klomek A, Barzilay S, Apter A, et al (2019)

Bi-directional longitudinal associations between different types of bullying victimization, suicide ideation/attempts, and depression among a large sample of European adolescents.

Journal of child psychology and psychiatry, and allied disciplines, 60(2):209-215.

BACKGROUND: The association between bullying victimization and depression, suicide ideation and suicide attempts has been studied mainly in cross-sectional studies. This study aims to test the bidirectional effect and the chronicity versus sporadic effect of physical, verbal, and relational bullying victimization on suicidal ideation/attempts and depression.

METHODS: Longitudinal assessments with an interval of 3- and 12-months were performed within a sample of 2,933 adolescents (56.1% females; mean age 14.78, SD = .89) from 10 European countries, participating in the Saving and Empowering Young Lives in Europe (SEYLE) school-based multicenter control sample. Multilevel Structural Equation Models were used, controlling for sociodemographic variables. Victimization was considered chronic when a student was victimized in the first two time points and sporadic when it was reported only at one point but not in another.

RESULTS: Bidirectional prospective association between all types of victimization and depression were found. Among participants, who reported victimization once (but not twice), physical victimization, but not verbal and relational, was associated with later suicidal ideation and attempts. Chronic victimization of any type increased likelihood for later depression compared with sporadic and no-victimization. Chronic relational victimization increased the likelihood of later suicidal ideation, and chronic physical victimization increased the likelihood for suicidal attempts.

CONCLUSIONS: The results support the bidirectional effect of victimization and depression and indicate that there are complex longitudinal associations between victimization and suicidal ideation/attempts. Physical victimization may especially carry effect on suicidal risk over time. Interventions should focus on victimization as a cause of distress but also aim to prevent vulnerable adolescents from becoming targets of victimization.

RevDate: 2019-02-26

Katz H, Jafri H, Saad R, et al (2018)

Colonic Obstruction from an Unusual Cause: A Rare Case of Metastatic Invasive Ductal Carcinoma to the Colon.

Cureus, 10(5):e2588.

Colon metastasis from breast cancer is rare. Gastrointestinal (GI) metastasis is more frequently seen in patients with invasive lobular carcinoma of the breast compared to invasive ductal carcinoma; however, the most common sites of metastasis still remain the lymph nodes, lungs, liver, and bones. We describe a 68-year-old female with a remote history of invasive ductal carcinoma of the breast who presented with abdominal pain and a palpable mass. On imaging, she was found to have a colonic obstruction and underwent a right hemicolectomy that proved to be metastatic invasive ductal carcinoma of the breast.

RevDate: 2018-12-17
CmpDate: 2018-12-17

Painter HJ, Chung NC, Sebastian A, et al (2018)

Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development.

Nature communications, 9(1):2656.

Genome-wide analysis of transcription in the malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-h intraerythrocytic developmental cycle (IDC), suggesting that this process is highly dynamic and tightly regulated. Here, we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture, and quantify newly-synthesized RNA transcripts at every hour throughout the IDC. This high-resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all IDC stages. Using a statistical model to predict the mRNA dynamics contributing to the total mRNA abundance at each timepoint, we find varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs, thereby expanding our understanding of P. falciparum mRNA dynamics.

RevDate: 2019-04-26
CmpDate: 2019-04-26

Bayindir-Buchhalter I, Wolff G, Lerch S, et al (2018)

Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.

EMBO molecular medicine, 10(8):.

Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.

RevDate: 2019-05-10
CmpDate: 2019-05-10

Zubeldia-Plazaola A, Recalde-Percaz L, Moragas N, et al (2018)

Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis.

Breast cancer research : BCR, 20(1):65.

BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells.

METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples.

RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS.

CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.

RevDate: 2019-01-14
CmpDate: 2019-01-14

Graff-Baker AN, Orozco JIJ, Marzese DM, et al (2018)

Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.

Annals of surgical oncology, 25(10):3082-3087.

BACKGROUND: Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.

METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.

RESULTS: Differentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.

CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.

RevDate: 2018-12-02
CmpDate: 2018-11-05

Kase AM, Menke D, W Tan (2018)

Breast cancer metastasis to the bladder: a literature review.

BMJ case reports, 2018: pii:bcr-2017-222031.

Given the prevalence of breast cancer and the mortality associated with metastatic disease, it is imperative for physicians to not only be aware of common sites but also of rare metastatic destinations such as the bladder. A postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma, oestrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative, in remission for 9 years, presented to her primary care physician with concerns of increased urinary urgency, frequency and incontinence. The patient underwent cystoscopy with biopsy of an area of granulation tissue. Biopsy revealed adenocarcinoma consistent with breast primary. The common sites of metastases from breast cancer are lung, bone and liver. This case is unique where breast cancer was found to metastasise to the bladder. It is important for physicians to consider further investigation when a breast cancer survivor develops urinary symptoms even without haematuria.

RevDate: 2019-05-13
CmpDate: 2019-05-13

Finet JE, GA Wiggers (2018)

Pharmacologic Management of Cancer Therapeutics-Induced Cardiomyopathy in Adult Cancer Survivors.

Current heart failure reports, 15(4):270-279.

PURPOSE OF REVIEW: The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.

RECENT FINDINGS: Our review of the literature did not identify any prospective randomized clinical trial of CTIC in adult cancer survivors, neither published nor in progress. However, available data seem to suggest that, when managed with standard guideline-derived medical therapy, the outcomes of CTIC are comparable to that of idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this strategy is inadequate. Until new information becomes available, pharmacological management of CTIC must parallel that of IDC. However, implementation of such may be hindered by other cancer therapeutics-induced comorbidities and conditioned by the particular effects of heart failure pharmacotherapy on cancer outcomes. This work succinctly reviews these three areas, in the context of adult cancer survivors.

RevDate: 2018-10-29
CmpDate: 2018-10-29

Lan VTT, Son HV, Trang VL, et al (2018)

Methylation profiles of miR34 gene family in Vietnamese patients suffering from breast and lung cancers.

Molecular medicine reports, 18(2):2476-2484.

The three genes encoding small non‑coding microRNA (miR)34a, MIR34b and MIR34c act as tumor‑suppressor genes. Their aberrant expressions regulated by DNA methylation have been frequently found in various types of cancer. In the present study, the DNA promoter methylation profiles of the MIR34 gene family were analyzed using the methylation specific polymerase chain reaction in order to clarify their association with breast and lung cancer, non‑cancerous or normal adjacent tissues. The methylation frequency of MIR34a was significantly higher in breast cancer (49.37%) compared with normal adjacent tissues (30.38%). The methylation frequency of MIR34b/c was 59.49 and 62.03% in breast cancer and normal adjacent tissues, respectively. MIR34a methylation showed a significant concordance with that of MIR34b/c only in breast cancer tissue. MIR34a methylation was significantly associated with cancer and the invasive ductal carcinoma type of breast cancer (P=0.015 and P=0.02, respectively). Methylation frequency of MIR34a and MIR34b/c was 48.42 and 56.84% in lung cancer, and 47.22 and 51.39% in pulmonary diseases, respectively. No significant association was observed between the methylation status of MIR34a and MIR34b/c, and the clinicopathological features of lung cancer or with those of non‑cancerous pulmonary diseases. Promoter methylation of MIR34a and MIR34b/c occurs frequently and concomitantly in breast and lung cancer, as well as in pulmonary diseases tissues, but not in breast normal tissues adjacent to tumor. These results of the present study emphasize the involvement of MIR34 methylation in human diseases, including cancer. Furthermore, MIR34a methylation may be a promising marker for a subtype of breast cancer.

RevDate: 2018-11-14
CmpDate: 2018-11-08

Linjawi S, AlGaithy Z, Sindi S, et al (2018)

Regulation of Lipocalin-2 oncogene and its impact on gene polymorphisms on breast cancer patients in Jeddah, Saudi Arabia.

Saudi medical journal, 39(6):558-563.

OBJECTIVES: To identify the impact of Lipocalin-2 (LCN2) gene polymorphisms on breast cancer patients in western Saudi Arabia.

METHODS: It is a case control study in which blood samples of participants from Medical Reference Clinics and King Abdulaziz University Hospital in Jeddah, Saudi Arabia have been taken between 2014 and 2016. This study recruited 128 participants (50% control, 50% patients) and used Tetra-Primer amplification-refractory mutation system-polymerase chain reaction method for the detection of missense SNP (rs11556770). The study measured LCN2 plasma protein expression by enzyme-linked immunosorbent assay technique. Results: The results have shown that 100% of the genotypes were normal allele (G/G). In contrast, the plasma level of LCN2 was considerably elevated among patients as compared to control (p=0.001), and higher in invasive ductal carcinoma patients (p=0.001). The LCN2 protein expression in plasma level was significantly elevated among patients, particularly who demonstrated invasive ductal carcinoma. Conclusion: There is no significant relationship between breast cancer patients and LCN2 gene polymorphisms (rs11556770).

RevDate: 2018-11-14

Sakamoto S, Tsuruga Y, Fujii Y, et al (2018)

Intraductal tubulopapillary neoplasm of the pancreas presenting as recurrent acute pancreatitis: A case report.

International journal of surgery case reports, 48:122-125.

INTRODUCTION: The 2010 World Health Organization classification of intraductal neoplasms of the pancreas includes intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasms, the latter being a rare and new concept. ITPN sometimes cause acute pancreatitis; therefore, distinguishing ITPN from idiopathic acute pancreatitis is important but challenging.

PRESENTATION OF CASE: We present the case of a 72-year-old male who had recurrent pancreatitis for the past 2 years, his diagnosis was idiopathic acute pancreatitis. He was admitted to our hospital with severe acute pancreatitis and cholangitis due to intrapancreatic bile duct stenosis. After the treatment of cholangitis, contrast-enhanced computed tomography revealed a tumor at the pancreatic head. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the main pancreatic duct and distal bile duct, and adenocarcinoma was detected using brush cytology of the bile duct stricture and pancreatic juice. The patient was diagnosed with invasive ductal carcinoma and pancreaticoduodenectomy was performed. Histopathological findings revealed dilation of the pancreatic duct, and proliferation of columnar cells and cuboid epithelial cells in the main pancreatic duct of the pancreatic head. Mucus production was poor, and immunostaining results revealed ITPN. The patient is alive and do not exhibit signs of recurrence for 12 months.

DISCUSSION: ITPNs can cause acute pancreatitis, which can be challenging to preoperatively diagnose. ITPNs presenting as acute pancreatitis are rare, with reported only 5 cases.

CONCLUSION: It is important to be keep in mind that there is a possibility of ITPN after diagnosis of idiopathic acute pancreatitis.

RevDate: 2018-12-21
CmpDate: 2018-12-21

Awungafac G, Amin ET, Fualefac A, et al (2018)

Viral load testing and the use of test results for clinical decision making for HIV treatment in Cameroon: An insight into the clinic-laboratory interface.

PloS one, 13(6):e0198686.

BACKGROUND: The viral load (VL) in patients receiving antiretroviral therapy (ART) is the best predictor of treatment outcome. The anticipated benefits of VL monitoring depend on the actual uptake of VL test results for clinical decisions. The objective of this study was to assess the uptake and utilization of VL test results for clinical decisions on HIV treatment in Cameroon, from 2013 to 2017.

METHODS: This was a retrospective cohort analysis of data from files of patients receiving ART at Buea, Limbe, Bamenda and Bafoussam regional hospital HIV treatment centers. A simple random pick of six file blocks was performed in each shelf that corresponded to a year of initiation, and the contents of all selected files were reviewed and the information needed for the study entered a structured questionnaire. The data collected was recorded in Epi Info (version, and analyzed using SATA (version 12.1; StataCorp LP).

RESULTS: Eight hundred and thirty files were reviewed. The mean duration on ART was 39.4±12 months. Viral load testing uptake was 24.33% and only one VL test had been done by all patients. Approximately 65% of the patients did the first VL after more than 24 months on ART. The median turnaround (TAT) time for VL testing was 6 days (Interquartile range (IQR) 3-7days). Among 201 patients who did a VL test, 94.55% had VL suppression (≤1000copies/mm3). Approximately 54% of the patients with virologic failure were switched to a second-line regimen.

CONCLUSIONS: The uptake of viral load testing is low in North West, South West and West Regions of Cameroon. The current TAT for VL testing is plausible. The rate of switch to second line regimen is low. It is time to strengthen the scale up of VL testing and improve the rate of switch to second-line regimen in Cameroon.

RevDate: 2018-12-02
CmpDate: 2018-07-09

Liu JY, Zou LP, Wu HJ, et al (2018)

[Effects of ubiquitin-specific proteases 2-69 on proliferation of breast cancer cells].

Zhonghua bing li xue za zhi = Chinese journal of pathology, 47(6):455-460.

Objective: To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast. Methods: Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro. Results: The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells. Conclusions: USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.

RevDate: 2018-11-14
CmpDate: 2018-06-18

Yin L, Li J, Wei Y, et al (2018)

Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: A case report and literature review.

Medicine, 97(23):e10900.

RATIONALE: Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature.

PATIENT CONCERNS: A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]).

DIAGNOSES: Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient.

INTERVENTIONS: The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor.

OUTCOMES: The patient died of progressive disease 7 months post-operatively.

LESSONS: The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.

RevDate: 2018-12-02
CmpDate: 2018-06-14

Kharmoum S, M Soughi (2018)

[Toxidermy mimicking acute chemotherapy-induced lupus erythematosus].

The Pan African medical journal, 29:66 pii:PAMJ-29-66.

Acute chemotherapy-induced lupus erythematosus (ALE) is rare. A few cases have been reported in the literature criminalizing capecitabine, paclitaxel and docetaxel. We report the case of a 64-year old female patient without a history of autoimmune diseases or of drug allergy followed up for invasive ductal carcinoma in the right breast immediately metastatized to the liver and to the lymph nodes. After AC60 first line chemotherapy regimen (a total of 6 cycles), she was treated with docetaxel at a dose of 100 mg/m2. After 5 cycles, she had diffuse erythematous lesions on both hands, forearms, cheeks and on the peribuccal area. She underwent corticosteroid therapy with sun protection and could continue the same chemotherapy until the eighth cycle. Patient's evolution was marked by the progression of the disease. She was treated with capecitabine at a dose of 1250 mg/m2 twice a day. After six cycles she had erythematosquamous and itchy patches on the face resembling the wings of a butterfly (Panel A, Panel B) with oral ulceration and digital pulpitis (Panel C). This initially suggested acute chemotherapy-induced cutaneous lupus erythematosus. Biopsy suggested lichenoid toxidermia. Immunological assessment was performed to exclude chemotherapy-induced cutaneous lupus erythematosus, which showed anti-native DNA antibodies and negative anti-histone antibodies. Anti-nuclear antibody test is positive at 320; this test may be positive in 50-70% of patients with breast cancer, ENT or lymphoma. In the light of these results the diagnosis of toxidermia was the more likely.

RevDate: 2019-02-25
CmpDate: 2019-02-25

Mills MN, Yang GQ, Oliver DE, et al (2018)

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.

European journal of cancer (Oxford, England : 1990), 98:48-58.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC.

METHODS: A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome.

RESULTS: MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC.

CONCLUSION(S): Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments.

RevDate: 2018-11-14
CmpDate: 2018-10-16

Guo X, Li J, Zhang H, et al (2018)

Relationship Between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) Expressions and Tumor Molecular Classification, Clinical Pathological Parameters, and Prognosis in Breast Invasive Ductal Carcinoma.

Medical science monitor : international medical journal of experimental and clinical research, 24:3726-3735.

BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.

RevDate: 2018-06-15
CmpDate: 2018-06-15

Rusak A, Jablonska K, Piotrowska A, et al (2018)

The Role of CHI3L1 Expression in Angiogenesis in Invasive Ductal Breast Carcinoma.

Anticancer research, 38(6):3357-3366.

BACKGROUND/AIM: An increased level of chitinase 3 like 1 protein (CHI3L1) expression is observed in patients with cancer and may have potential prognostic value. The aim of this study was to evaluate the role of CHI3L1 in angiogenesis in invasive ductal breast carcinoma (IDC) (n=110).

MATERIALS AND METHODS: Immunohistochemistry was used to assess the expression of CHI3L1, CD31, CD34, vascular endothelial growth factor (VEGFA, VEGFC and VEGFD). Real-time polymerase chain reaction and western blot were used to determine the level of CHI3L1 mRNA and protein.

RESULTS: Immunohistochemistry demonstrated positive correlation between CHI3L1 expression and angiogenesis markers: CD31 (r=0.34, p=0.0003), CD34 (r=0.24, p=0.012), VEGFD (r=0.24, p=0.013). Higher CHI3L1 expression in estrogen receptor-negative (p=0.041) and progesterone receptor-negative (p=0.014) cancer was observed. Higher CHI3L1 expression was reported in cancer tissues in comparison to non-malignant breast lesions.

CONCLUSION: These results suggest a potential role of CHI3L1 in angiogenesis in IDC and may suggest its involvement in cancer progression.

RevDate: 2018-11-14
CmpDate: 2018-10-30

Santangelo G, Bisecco A, Trojano L, et al (2018)

Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.

Journal of neurology, 265(8):1772-1779.

Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.

RevDate: 2018-10-11
CmpDate: 2018-10-11

Schellenberg AE, Wood ML, Baniak N, et al (2018)

Metastatic ductal carcinoma of the breast to colonic mucosa.

BMJ case reports, 2018: pii:bcr-2018-224216.

Breast cancer is the most common malignancy among women, while invasive ductal carcinoma is the most common type of invasive breast cancer. Metastatic spread to the colon and rectum in breast cancer is rare. This report describes a case of a 69-year-old woman with metastatic ductal breast cancer to the rectosigmoid, presenting as an incidental finding on screening colonoscopy. The breast carcinoma was first diagnosed 2 years prior. Colonic biopsies from colonoscopy confirmed metastatic adenocarcinoma consistent with a breast primary. Ultimately her clinical condition worsened as she developed malignant ascites, a small bowel obstruction, and new bone metastases, and the patient succumbed to her illness. Cases of metastatic breast cancer to the gastrointestinal tract have predominantly been lobular breast carcinoma. Increased awareness of colonic metastasis may lead to more accurate diagnosis and earlier systemic treatment.

RevDate: 2018-11-14
CmpDate: 2018-08-03

Di Oto E, Biserni GB, Varga Z, et al (2018)

X chromosome gain is related to increased androgen receptor expression in male breast cancer.

Virchows Archiv : an international journal of pathology, 473(2):155-163.

X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.

RevDate: 2018-11-14

Nahleh Z, Otoukesh S, Mirshahidi HR, et al (2018)

Disparities in breast cancer: a multi-institutional comparative analysis focusing on American Hispanics.

Cancer medicine, 7(6):2710-2717.

Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico- pathological characteristics and disparities in breast cancer in this group at two tertiary care University-based medical centers. After IRB approval, Cancer registry was used to analyze the variables of 3441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical and cancer center database centers in El Paso, TX and Loma Linda, CA between 2005 and 2015. Association between race/ethnicity and cancer type, stage, hormone receptor status and treatment option were investigated. Overall 45.5% of the patients were Hispanic (n: 1566) and those were more likely to be diagnosed at a younger age (57 years) similar to African Americans, more likely to have invasive ductal carcinoma type (82.7%) & triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have hormone receptor (HR)+ & HER2- as opposed to 71% in non-Hispanic White people. In addition, Hispanic individuals presented with advanced stages of BC (25.3%, 95% CI: 23% to 28%) similar to African American (25.4%), and had a lower proportion of lumpectomy (50%) similar to African American (50%). When compared to African American patients, Hispanic patients had a higher prevalence of triple negative BC (17.11% in Hispanics Versus 13.86% in African American).

CONCLUSION: Hispanics had significantly higher relative risk of advanced stages at presentation (Relative Risk Ratio (RRR) = 2.05, P < 0.001), triple negative tumors (RRR = 2.64, P < 0.0001), HER2 + /HR - disease (RRR = 1.77, P < 0.0001), and less HR+ /HER2- BC (RRR = 0.69, P < 0.0001). Hispanics and African Americans are diagnosed with breast cancer at a younger age, have a higher prevalence of Triple negative breast cancer, and are diagnosed at more advanced stages of disease. Increasing awareness and targeting minority populations for health promotion interventions, screening and early detection continue to be of paramount importance to reduce the burden of health disparities.

RevDate: 2018-11-14
CmpDate: 2018-05-07

Xie L, Lin C, Zhang H, et al (2018)

Second malignancy in young early-stage breast cancer patients with modern radiotherapy: A long-term population-based study (A STROBE-compliant study).

Medicine, 97(17):e0593.

Second cancer is a leading cause of death in long-term survivors of younger early-stage breast cancer patients. To date, relationship of age, receipt of radiotherapy (RT), and estimated doses received by target organs have not yet been well elucidated. Using Surveillance, Epidemiology, and End Results database, patients aged 20 to 44, diagnosed with a first primary staging I-IIIA ipsilateral breast invasive ductal carcinoma, underwent surgery during 1988 to 2009 were identified, and those with a second malignancy at ≥1-year follow-up were analyzed to calculate cumulative incidences (CIs) of second malignancy in whole group and each subgroup. Subgroups were dichotomized by surgery type, axillary dissection, and axillary lymph node status. With a median follow-up of 11.8 years, 22,628 women including 1495 patients (6.6%) developing second malignancies (3.7% contralateral breast cancer, 2.9% non-breast second malignancies, and 0.7% high-dose site second malignancies) were identified. Three-dimensional coordinate systems with age at primary diagnosis, time after primary breast cancer diagnosis, and CI of second malignancy as 3 axes, for endpoints including all second malignancy, second primary contralateral breast cancer, and non-breast second malignancy were presented, along with the risk in RT and non-RT groups in overall group and subgroups. Five-, 10-, 15-, and 20-year all second malignancy-free survivals in RT and non-RT groups were 89.5% versus 85.4%, 80.1% versus 75.0%, 72.9% versus 67.9%, and 65.6% versus 61.8% (P < .0001). From the large national dataset, a broad visualized overview of second malignancy risk, including second contralateral breast cancer and non-breast second cancer, suggests generally beneficial therapeutic ratio for radiotherapy in young women with early-stage breast cancer.

RevDate: 2018-11-14
CmpDate: 2018-10-10

Rahmani M, Nili F, E Tabibian (2018)

Endometrial Metastasis from Ductal Breast Carcinoma: A Case Report with Literature Review.

The American journal of case reports, 19:494-499.

BACKGROUND There are few reports of breast cancer cases with uterine metastases; among them, myometrium is more frequently involved than endometrium. The majority of breast cancer metastases to endometrium are lobular type, and there have been only 5 reported cases of ductal type since 1984. Here, we describe a new case of invasive ductal carcinoma with metastases to endometrium and isolated presentation of abnormal uterine bleeding, in addition to reviewing the existing literature on other similar cases. CASE REPORT The patient was a 51-year-old Persian woman with no remarkable past medical or family history of cancer, who presented with a 6-month complaint of menorrhagia to our gynecology clinic. Diagnostic studies including trans-vaginal ultrasonography, pathological examination of endometrial curettage specimen, immunohistochemistry findings, and X-plane and magnetic resonance mammography, and breast core-needle biopsy revealed invasive ductal breast carcinoma as the origin of the endometrial metastasis. CONCLUSIONS Abnormal uterine bleeding in a premenopausal patient should alert clinicians to the possibility of secondary as well as primary neoplasms. It is necessary to differentiate a metastatic tumor from a primary one, since the treatment and prognosis are completely different.

RevDate: 2019-06-10

Bharti R, Dey G, Das AK, et al (2018)

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

British journal of cancer, 118(11):1442-1452.

BACKGROUND: Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis.

METHODS: We employed various in-vitro and in-vivo techniques and clinical samples.

RESULTS: We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen.

CONCLUSIONS: Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )