Assessment of Nerve Fiber Density and Expression of Hormonal Receptors Within Rectosigmoid Endometriosis Nodules.

STUDY OBJECTIVE: To assess nerve fiber density and expression of hormone receptors in bowel endometriosis. DESIGN: Cross-sectional study. SETTING: Private hospital. PATIENTS: Women with endometriosis undergoing laparoscopic segmental bowel resection (n = 54). INTERVENTIONS: Tissue samples were obtained from patients with surgically treated rectosigmoid endometriosis. MEASUREMENTS AND MAIN RESULTS: The rectosigmoid specimen containing the endometriosis nodule was manually sectioned and divided into 3 areas: core of the nodule, margin of the nodule, and healthy bowel tissue. The intensity of expression of estrogen and progesterone receptors was evaluated by immunohistochemistry and measured according to the Allred score. Nerve fibers were stained by immunohistochemistry using Protein Gene Product 9.5, and the density of nerve fillets was counted and expressed in number/mm². All glandular and stromal cells stained for estrogen; however, glandular cells stained more strongly than stromal cells (61.1% vs 35.2%; p = .01). Most of glandular and stromal cells stained strongly for progesterone receptors (90.7% vs 98.1%; p = .2). The density of nerve fibers was very high in the margin of the nodule (172.22±45.66/mm²), moderate in healthy bowel tissue (111.48±48.57/mm²), and very low in the core of the nodule (7.31±4.9/mm²); p = .01. CONCLUSION: Both glandular and stromal cells within the rectosigmoid endometriosis nodule express estrogen and progesterone receptors. Higher intensity of expression of estrogen receptors occurs in glandular cells. The density of nerve fibers is extremely high at the nodule margin and very low in the center of the nodule.

A cumulative index of exposure to endogenous estrogens and breast cancer by molecular subtypes in northern Mexican women.

PURPOSE: To evaluate breast cancer (BC) molecular subtypes association with reproductive characteristics and an index of cumulative exposure to endogenous estrogens (EEI) in Mexican women. METHODS: We performed a study of incident cases and population controls in northern Mexico. We included BC cases with tumor molecular classification in their medical records (n = 509), and classified them as HR+/HER2- (ER+ and/or PR+ and HER2-) (n = 289), HER2+ (HR+ or HR-) (n = 117) or triple negative (TN) (n = 103). We matched controls (n = 1030) by age and place of residence with index cases. Women were interviewed about their reproductive history, from which the EEI was developed. We used logistic regression models to estimate BC molecular subtypes associations with reproductive characteristics and EEI. RESULTS: The EEI was higher in all subtypes compared to controls (Median HR+/HER2- 27.25, HER2+ 26.8, TN 24.2 vs. controls 22.8 years, p < 0.05), and was associated with HR+/HER2- (ORT3 vs. T1 = 2.58, 95% CI 1.77-3.55, p-trend < 0.001) and HER2+ (ORT3 vs. T1 = 4.17, 95% CI 2.15-8.08, p-trend < 0.001) BC. Additionally, HR+/HER2- tumors were positively associated with age at first pregnancy and age at menopause, and negatively with age at menarche, parity and breastfeeding. The HER2+ subtype was associated in the same direction as HR+/HER2- tumors with all the reproductive characteristics except for age at menarche. TN tumors were negatively associated with parity and breastfeeding. CONCLUSION: Endogenous estrogens exposure throughout Mexican women reproductive life may contribute to the development of all but TN BC, however, these findings should be confirmed in other Hispanic populations.

Diabetes mellitus and prostate cancer metabolism: Is there a relationship?

OBJECTIVE: Our aim was to evaluate the effects of glucose levels and diabetes mellitus in prostate cancer (PCa) biology. MATERIALS AND METHODS: Two PCa cell lines (LNCap and PC3) were cultured in RPMI medium with different glucose concentrations [5mM (LG) and 25mM (HG)]. Expressions of androgen receptor, Her2/neu and glucose transporters (GLUT1, 3, 5 and 12) were evaluated by flow cytometry. Proliferation rate was assessed by colorimetric assay MTT and cellular characterization was performed by haematoxylin and eosin staining. Additionally, we performed a cross sectional analysis of 704 patients undergoing radical prostatectomy who were divided into two groups (diabetic and non-diabetic). An analysis of clinical and histological data seeking to identify the differences on tumor aggressiveness between the two groups was performed. RESULTS: In LNCaP cell line, when the glucose concentration in the medium increased, there was an increased in AR expression. Regarding expression of Her2/neu receptor, medium's glucose concentration significantly changed the expression of this receptor in both PC3 and LNCaP cell lines. Growth rate was higher on the HG medium for both cell lines. The clinical study of patients undergoing radical prostatectomy revealed no relationship between the presence of diabetes and the development of more aggressive tumours. Diabetic patients had significantly higher prostatic volumes, however, no significant difference was found between the relapse risk classification or the ISUP classification between the two groups. CONCLUSIONS: Our results showed that medium glucose concentration could influence prostate cancer cells growing but not the aggressiveness.

Aggressive digital papillary adenocarcinoma: A clinicopathological study of 19 cases.

BACKGROUND: Aggressive digital papillary adenocarcinomas (ADPA) are malignant tumors of sweat glands having recurrence/metastatic potential. OBJECTIVE: We sought to describe the clinical/histopathological characteristics of a series of ADPA. METHODS: This is a retrospective case series of 19 ADPA. RESULTS: The tumors occurred in 17 men and 2 women (mean age: 47 years). They involved digits (15), big toe (3), and palm (1), and measured from 3 to 30 mm. They were mostly solid and cystic, with papillary projections and tubular structures. Atypia was mostly mild to moderate. Tumors tested positive for p63, keratin 7, keratin 77 (eccrine duct-specific), PHLDA1, and epithelial membrane antigen in most cases, and for carcinoembryonic antigen, smooth muscle actin, S100 protein, estrogen, progesterone, and androgen receptors in 50%. Mean Ki67 proliferation index was 15%. Local recurrence was observed in 4 cases. One patient had axillary lymph node metastasis. Histopathologic parameters were not predictive of evolution. Conservative surgical treatment, performed in 7 of 19 cases, did not result in more recurrences than amputation. LIMITATIONS: The study was retrospective and the number of cases is small. CONCLUSION: ADPA are histologically variable, but papillary projections are always present. Keratin 77 expression suggests an eccrine origin. P63 is helpful to exclude metastasis. Conservative surgery may be sufficient in some cases.

Spontaneous resolution of visual loss due to optic pathway meningioma: A case report and a review of the literature.

BACKGROUND/AIM: Meningiomas of the anterior cranial fossa are often diagnosed after impaired visual function occurrence. Some epidemiologic studies suggest an association between exogenous or endogenous hormones and meningioma risk. The aim of this study is to briefly review the literature and relate a case report. PATIENT AND METHODS: This study presents a case of a 51-year-old woman with a moderate visual loss of 6/10 and markedly constricted visual field in the right eye. A normal visual acuity and peripheral reduction of visual field in the left eye was documented. During medical interview, she reported a prolonged assumption of oral contraceptive. Her visual deterioration had progressed over the previous 3 months and was associated with occasional headache. MRI scanning showed a small optic pathway meningioma. RESULTS: After various examinations, it was decided to 'wait and see' and no therapy was administered. The patient noticed a progressive improvement in the vision in her right eye, with corresponding improvement in the bilateral visual field. CONCLUSION: The case reports on the spontaneous resolution of visual loss due to the volume reduction of the anterior visual pathway compressive intracranial meningioma after interruption of prolonged assumption of oral contraceptive and focuses on the correlation between sexual hormone pathway and intracranial meningioma.

Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients. PATIENTS AND METHODS: We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery. RESULTS: We identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54-1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40-0.68 P < 0.0001) and overall survival (HR 0.45; 95% CI 0.32-0.64, P < 0.0001). CONCLUSION: The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.

Reconstruction of functional endometrium-like tissue in vitro and in vivo using cell sheet engineering.

Uterus is a female specific reproductive organ and plays critical roles in allowing embryo to grow. Therefore, the endometrial disorders lead to female infertility. Hence, the regeneration of endometrium allowing fertilized ovum to implant might be valuable in the field of fertility treatment. Recently, cell sheet engineering using a temperature-responsive culture dish has advanced in regenerative medicine. With this technology, endometrial cells were harvested as a contiguous cell sheet by reducing temperature. Firstly, mouse endometrial cell sheets were re-cultured for 3 days to evaluate the function. Histological analyses revealed that endometrial epithelial cell-specific cytokeratin 18 and female-specific hormone receptors, estrogen receptor ß and progesterone receptor, were expressed. Furthermore, endometrial epithelial cells constructed epithelial layer at the apical side. Then, endometrial cell sheets from green-fluorescent-protein rat cells were transplanted onto the buttock muscle of nude rat for evaluating the function in vivo. Histological analyses showed that endometrial cell sheets reconstructed endometrium-like tissue, which was found to form uterus-specific endometrial glands having hormonal receptor to estrogen. In this study, endometrial cell sheets were speculated to contribute to the regeneration of functional endometrium as a new therapy.

Quantitative Real Time PCR assessment of hormonal receptors and HER2 status on fine-needle aspiration pre-operatory specimens from a prospectively accrued cohort of women with suspect breast malignant lesions.

OBJECTIVES: Reliable assessment of estrogen, progesterone (ER and PR), and HER2 receptor status are essential in breast cancer (BC) treatment. Immunohistochemical methods are limited by intra- and inter-laboratory variability. Furthermore, current methods are not the ideal approach for reproducing the biological continuum of ER, PR, and HER2 receptor levels, due to their intrinsic, semi-quantitative nature, relying in part on subjective interpretation. METHODS: In the present study, we tested a molecular approach to define ER, PR, and HER2 status in fine-needle-aspirate (FNA) samples from patients with early BC. We performed flow cytometry analysis on 88 FNA specimens from suspect BC patients to determine cellularity. We used quantitative Real Time PCR (QRT-PCR) to assess ER, PR, HER2 status, and qPCR for HER2 gene copy number (GCN). RESULTS: ER and PR mRNA levels showed a highly significant correlation with IHC data on surgical samples. qPCR showed greater accuracy than IHC in defining HER2 status. QRT-PCR defined better than IHC the continuous spectrum of the expression of the assessed receptors. Moreover, PCR analysis demonstrated a strict correlation between HER2 status and higher levels of its transcript, correctly stratifying HER2+ and HER2- patients. Finally, there was a strongly significant agreement between HER2 GCN assessed on FNA specimens by qPCR and FISH data obtained on pathological tissue specimens. CONCLUSIONS: The present results support a comprehensive approach to determine ER, PR, and HER2 status by PCR (QRT-PCR and qPCR) in FNA specimens, with high relevance for therapeutic strategies like neoadjuvant treatment.

Androgen receptor markers do not differ between nonresponders and responders to resistance training-induced muscle hypertrophy.

The aim of this study was to investigate whether baseline values and acute and chronic changes in androgen receptors (AR) markers, including total AR, cytoplasmic (cAR) and nuclear (nAR) fractions, as well as DNA-binding activity (AR-DNA), are involved in muscle hypertrophy responsiveness by comparing young nonresponder and responder individuals. After 10 weeks of resistance training (RT), participants were identified as nonresponders using two typical errors (TE) obtained through two muscle cross-sectional area (mCSA) ultrasound measurements (2×TE; 4.94%), and the highest responders within our sample were numerically matched. Muscle biopsies were performed at baseline, 24h after the first RT session (acute responses) and 96h after the last session (chronic responses). AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Twelve participants were identified as nonresponders (ΔmCSA: -1.32%), and twelve as responders (ΔmCSA: 21.35%). There were no baseline differences between groups in mCSA, AR, cAR, nAR or AR-DNA (P > 0.05). For acute responses, there was a significant difference between nonresponders (+19.5%) and responders (-14.4%) in AR-DNA (ES = -1.39; 95% CI: -2.53 to -0.16; P = 0.015). There were no acute between-group differences in any other AR markers (P > 0.05). No significant differences between groups were observed in chronic responses across any AR markers (P > 0.05). Nonresponders and responders presented similar baseline, acute and chronic results for the majority of the AR markers. Thus, our findings do not support the influence of AR markers on muscle hypertrophy responsiveness to RT in untrained individuals.

Exposure to Organochlorine Pesticides and Female Breast Cancer Risk According to Molecular Receptors Expression: a Systematic Review and Meta-analysis of Epidemiological Evidence.

PURPOSE OF REVIEW: Organochlorine pesticides (OCP) have been proposed as potential mammary carcinogens since they interact with steroid signaling pathways. However, the epidemiological results are not conclusive. Most studies have evaluated breast cancer (BC) as a single entity without considering the different molecular expressions, including estrogen receptor (ER), progesterone receptor (PR), and HER2, that could differ in their association with these contaminants. Hence, we assessed the association between biological concentration of OCP and BC, according to its molecular receptor expression, based on a systematic review and meta-analysis. RECENT FINDINGS: Of the 141 articles eligible for full-text review, nine met the inclusion criteria. The way in which molecular expression was reported was heterogeneous; therefore, the inclusion of studies in the meta-analysis was limited to eight articles. A negative association was identified for ß-hexachlorocyclohexane and trans-nonachlor with ER + tumors and between hexachlorobenzene and ER - tumors. No associations were observed for p,p'-dichlorodiphenyldichloroethylene, cis-nonachlor, and dieldrin, and it was not possible to evaluate the associations between OCP with HER2 expression or triple-negative tumors due to lack of data. The results suggest that some OCP might be associated with BC depending on the expression of ER. However, the evidence is not conclusive due to the scarce data. We identified several methodological aspects to fill the gaps in knowledge and increase the comparability among studies.

Agreement between incisional and excisional biopsies for hormone receptors and her2 in breast cancer.

INTRODUCTION: Breast cancer is the leading cause of cancer mortality in Mexican women. OBJECTIVE: The objective of the study was to identify concordances among core needle biopsy (CNB) and excisional biopsies (EB) regarding diagnosis, hormonal receptors (HR), and human epidermal growth factor receptor 2 (Her2). MATERIALS AND METHODS: Core number, demographic data, histological type, and treatment were documented for each sample. Reported HR and Her2 score from both samples were compiled. RESULTS: 70 women with both CNB/EB were included. Median age was 58 (36-87) years; initial diagnosis in CNB were invasive ductal 56 (80%), lobular 10 (14%), and mixed 4 (6%) carcinomas. Diagnostic agreement among CNB and EB was of 97%, k = 0.65. A concordance of 92% (k = 0.75), 75% (k = 0.26), and 67% (k = 0.46) was observed for estrogen receptors, progesterone receptors, and Her2 determinations, and positive predictive values in CNB were 0.96, 0.89, and 0.44, respectively. CONCLUSION: HR and Her2 concordances using manual-immunohistochemistry (IHC) were found within the range of values obtained using automatized-IHC. When compared to tumor heterogeneity, technical/reading errors contribute more to discordances.

INTRODUCTION: El cáncer de mama es la principal causa de mortalidad por cáncer en mujeres mexicanas. OBJETIVO: Identificar la concordancia entre la biopsia con aguja de corte (BAC) y la biopsia escisional (BE) con respecto al diagnóstico, receptores hormonales (RH) y Her2. MATERIAL Y MÉTODOS: Se registró el número de fragmentos cilíndricos, datos demográficos, tipo histológico y tratamiento. Se recopilaron resultados de RH y Her2. RESULTADOS: Se incluyeron 70 mujeres con mediana de edad de 58 años. El diagnóstico inicial en BAC fue carcinoma ductal invasivo 56 (80%), lobular 10 (14%) y mixtos 4 (6%). El acuerdo de diagnóstico entre BAC y BE fue del 97%, k = 0.65. Se observó una concordancia de 92% (k = 0.75), 75% (k = 0.26) y 67% (k = 0.46) para las determinaciones de receptor de estrógenos (RE), receptor de progesterona (RP) y Her2, y los valores predictivos positivos en BAC fueron 0.96, 0.89 y 0.44, respectivamente. CONCLUSIÓN: Los RH y la concordancia de Her2 mediante inmunohistoquímica (IHC) manual se encuentran dentro del rango de valores obtenidos mediante el uso de IHC automatizada. Los errores técnicos/de lectura contribuyeron más a discordancia que la heterogeneidad tumoral.

Prognostic value of androgen receptor expression in different molecular types of breast cancer in women.

BACKGROUND: Breast cancer is a common women's disease. Usually, oestrogen is blamed in the aetiology and correlated with the prognosis; however, androgens are recently raising concern about its role in the breast cancer treatment and prognosis. METHODS: In this study we retrieved archival paraffin blocks of breast cancer patients and stained it for androgen. Thereafter, we compared clinico-epidemiologic parameters, histopathology, neoadjuvant response and recurrence rate and pattern among patients with and without androgen receptor (AR) expression. RESULTS: In total, 119 patients fulfilled enrolment criteria; AR expression were present in 77.3% of the patients. AR expression was associated with less grade III (6.8% versus 36.4%), and less triple negative (6.2% versus 25%), but similar overall recurrence rate (25% versus 22.2%). However, distant recurrence was significantly higher in androgen positive patients (91.3% versus 33.3% of all recurrences). CONCLUSION: Androgen expression appears to be common among breast cancer, but with no clear implication in tumour aggressiveness or effect on the rate of recurrence. However, being commonly associated with distant spread may have an impact on survival of the patients.

Factors Predicting Positive Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer.

Purpose: Sentinel lymph node (SLN) biopsy (SLNB) is the standard tool to stage the axilla of breast cancer patients. This study aimed to identify the predictors of positive SLNB in patients with clinically node-negative breast cancer. Patients and Methods: A retrospective, single-institution cohort of patients with early-stage breast cancer without clinically identifiable axillary lymphadenopathy was chosen from January 2010 to December 2018. Logistic regression was used to identify possible predictors of positive SLNB. Results: Four hundred and seventy patients were identified; their mean age was 50±11 years. Most patients had the following characteristics: invasive ductal carcinoma (n=382, 81.3%), unilateral tumor (n=461, 98.1%), unifocal disease (n=351, 74.7%), intermediate grade (n=276, 59.0%), and estrogen and progesterone receptor positivity with human epidermal growth factor receptor 2 negativity (n=305, 64.9%). The mean size of the breast mass was 2.3±1.5 cm. SLNB was positive in 128 (27.2%) cases. The mean number of SLNs was 2±1.2. Axillary lymph node dissection was performed in 109 patients. The mean number of lymph nodes removed was 15±6. In 66 (60.6%) of the 109 patients with metastatic axillary nodes, only the SLNs were found to be positive. The number of SLNs, tumor size, tumor grade, receptor status, prominent axillary lymph nodes, and lymphovascular invasion predicted positive SLNB (P = 0.01, 0.03, 0.03, and 0.04 and <0.001 and <0.001, respectively). Conclusion: Our results suggest that a number of histopathological and radiological characteristics of breast cancer can predict SLNB positivity in clinically node-negative breast cancer patients.

Impact of immunohistochemical profile changes following neoadjuvant therapy in the treatment of breast cancer.

INTRODUCTION: Currently, the indication for neoadjuvant chemotherapy is increasing in the treatment of breast cancer. Variability in the expression of biomarkers following neoadjuvant treatment has been observed, which could be accompanied by changes in the adjuvant treatment. OBJECTIVES: The primary objective was to evaluate the variability of biomarkers prior to and following neoadjuvant therapy. Secondary objectives were to determine which tumour subtype (as determined by immunohistochemical markers) most frequently achieved pathological complete response (pCR); whether the biomarker variation resulted in a change in immunophenotype and subsequently modification to the adjuvant treatment. MATERIALS AND METHODS: A retrospective observational analysis was carried out on patients with a diagnosis of breast cancer who had neoadjuvant therapy prior to surgery in the Breast Care Service of the Buenos Aires British Hospital between January 2009 and June 2020. RESULTS: One hundred and seventy-two patients were included. The pCR rate was 28.5%. The tumour immunophenotype that achieved pCR most frequently was the hormone receptor negative /HER2+ group with a value of 85.2%. The analysis was carried out on the 123 patients with residual disease. The observed variability for oestrogen receptors (ER) was 8.9%, for progesterone receptors (PR), 29.9% and for HER2, 13.8%. These changes were statistically significant. There were changes to the tumour immunophenotype in 26 cases (21.1%) with modifications to the adjuvant treatment in nine of these (34.6%; 7.3% of all tumours with residual disease). CONCLUSIONS: In this study, we observed statistically significant variability in the expression of ER, PR and HER2 prior to and following neoadjuvant treatment, which identified modifications in the tumour immunophenotype in 21.1%, and changes to the adjuvant treatment in 7.3% of all tumours with residual disease, justifying the re-assay of biomarkers in the surgical specimen.

Analysis of Increased EGFR and IGF-1R Signaling and Its Correlation with Socio-Epidemiological Features and Biological Profile in Breast Cancer Patients: A Study in Northern Brazil.

INTRODUCTION: Breast cancer (BC) is the second most frequent cancer worldwide. It is known that a subset of BC has amplification, and overexpression of the epidermal growth factor receptor (EGFR) and high expression of the insulin-like growth factor receptor-1 (IGF-1R) are correlated with a favorable prognosis. This study aimed to evaluate the prognostic and predictive values of the EGFR and IGF-1R in tumor samples from patients with BC and their correlation with socio-epidemiological features. PATIENTS AND METHODS: We analyzed socio-epidemiological, clinical-pathological data and tumor tissues from 124 patients with BC undergoing treatment, to assess levels of EGFR and IGF-1R mRNA and protein. The predictive performance included the calculation of area-under-the-curve (AUC) to discriminate groups of patients with high and low mRNA expression associated with survival analysis within each molecular group of BC. RESULTS: We found a significant expression increase (p <0.001) in EGFR associated with body mass index, angiolymphatic invasion, compromised lymph nodes and follow-up in 58.1% of the triple-negative and HER overexpression tumors. The increase in IGF-IR was significant (p <0.001) in 41.9% of luminal tumors A and B. ROC analysis showed that EGFR had a higher predictive performance (AUC = 0.891) than IGF-1R (AUC = 0.60). The Kaplan-Meier analysis indicated that only the high expression of EGFR was associated with a decreased probability of survival for patients, what did not happen with IGF-1R. CONCLUSION: Our results suggest that EGFR and IGF-1R expression patterns associated with the clinical characteristics of patients and biological profile influenced the evolution of BC.

MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines.

Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15-20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.

Efficiency of microbial bio-agents as elicitors in plant defense mechanism under biotic stress: A review.

Numerous harmful microorganisms and insect pests have the ability to cause plant infections or damage, which is mostly controlled by toxic chemical agents. These chemical compounds and their derivatives exhibit hazardous effects on habitats and human life too. Hence, there's a need to develop novel, more effective and safe bio-control agents. A variety of microbes such as viruses, bacteria, and fungi possess a great potential to fight against phytopathogens and thus can be used as bio-control agents instead of harmful chemical compounds. These naturally occurring microorganisms are applied to the plants in order to control phytopathogens. Moreover, practicing them appropriately for agriculture management can be a way towards a sustainable approach. The MBCAs follow various modes of action and act as elicitors where they induce a signal to activate plant defense mechanisms against a variety of pathogens. MBCAs control phytopathogens and help in disease suppression through the production of enzymes, antimicrobial compounds, antagonist activity involving hyper-parasitism, induced resistance, competitive inhibition, etc. Efficient recognition of pathogens and prompt defensive response are key factors of induced resistance in plants. This resistance phenomenon is pertaining to a complex cascade that involves an increased amount of defensive proteins, salicylic acid (SA), or induction of signaling pathways dependent on plant hormones. Although, there's a dearth of information about the exact mechanism of plant-induced resistance, the studies conducted at the physiological, biochemical and genetic levels. These studies tried to explain a series of plant defensive responses triggered by bio-control agents that may enhance the defensive capacity of plants. Several natural and recombinant microorganisms are commercially available as bio-control agents that mainly include strains of Bacillus, Pseudomonads and Trichoderma. However, the complete understanding of microbial bio-control agents and their interactions at cellular and molecular levels will facilitate the screening of effective and eco-friendly bio-agents, thereby increasing the scope of MBCAs. This article is a comprehensive review that highlights the importance of microbial agents as elicitors in the activation and regulation of plant defense mechanisms in response to a variety of pathogens.

Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor.

INTRODUCTION: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. AREAS COVERED: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. EXPERT OPINION: As shown in phase 2 and 3 clinical trials on efficacy and tolerability, abemaciclib is a potentially convenient, safe, and effective agent for the treatment of patients with advanced hormone receptor-positive patients. Orally administered abemaciclib in combination with aromatase inhibitors or fulvestrant has the potential to allow significant improvement in survival outcomes, quality of life, response rate, and duration of response even in poor prognosis subgroups. Adequate patients' information, clinical selection, and prompt, proactive management of side effects are mandatory.

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing in Women with Breast Cancer in Kampala, Uganda.

BACKGROUND: The expression of estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor-2 (HER2) has been reported to have an invaluable prognostic role. The aim of this study was to determine the expression of ER, PR and HER2 in women with breast cancer (BC) in Kampala, Uganda. METHODS: Expression of ER, PR and HER2 was determined immunohistochemically. Logistic regression was performed to determine the effect of the independent factors in predicting the risk of not expressing the breast markers. A two-tailed p<0.05 was regarded to be statistically significant. RESULTS: ER, PR and HER2 were expressed in 53.4%, 46.6% and 18.5%, respectively. ER and PR co-expression was present in 42.7% and 37.9% patients had triple negative breast cancer (TNBC). Age was an independent predictor of expression of ER (AOR = 0.18, 95% CI = 0.062-0.541, p = 0.002) and PR (AOR = 0.35, 95% CI = 0.129-0.968, p = 0.043). CONCLUSION: The majority of patients in this study had less than 50 years with high tumour grade. Interestingly, most of them had high expression of HER2 with TNBC which are molecular subtypes of BC with poor prognosis. Age was an independent predictor of expression of both ER and PR.

EO771, is it a well-characterized cell line for mouse mammary cancer model? Limit and uncertainty.

Among mouse mammary tumor models, syngeneic cell lines present an advantage for the study of immune response. However, few of these models are well characterized. The tumor line EO771 is derived from spontaneous breast cancer of C57BL/6 mice. These cells are widely used but are referenced under different names: EO771, EO 771, and E0771. The characteristics of the EO771 cells are well described but some data are contradictory. This cell line presents the great interest of developing an immunocompetent neoplastic model using an orthotopic implantation reflecting the mammary tumors encountered in breast cancer patients. This review presents the phenotype characteristics of EO771 and its sensitivity to nutrients and different therapies such as radiotherapy, chemotherapy, hormone therapy, and immunotherapy.