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Background: Bladder carcinoma (BC) ranks second among the genitourinary cancers worldwide. Influence of androgens and expression of androgen receptors in neoplasms are recent findings which were implicated in the development of BC. We aimed to study androgen receptor (AR) expression in bladder urothelial neoplasms and correlate its expression with grade and stage of the tumor. Methods: Immunohistochemistry (IHC) was done on samples collected in a tertiary care hospital over one year consisting of 71 urothelial BC and 20 non-neoplastic urothelial conditions. Two pathologists graded the IHC and nuclear staining was considered as positive expression. Results: AR was expressed in 23.9% (17/71) of bladder urothelial neoplasms. AR was expressed in 25.7% and 22.3% of high and low-grade tumors and 25% and 22.3% of non muscle-invasive and muscle-invasive BC. AR expression had no significant correlation with gender, age (> 50 years), muscle invasion or grade. AR expression was significantly absent in non-neoplastic conditions (p = 0.018). Conclusions: AR has varied expression in BC and it is relatively lower in this study population.

Quadruple-negative breast cancer (QNBC) presents with negative expression of estrogen, progesterone, and androgen receptors and of human epidermal growth factor receptor 2. This BC subtype has the worst prognosis. In QNBC, there is a greater paucity of prognostic biomarkers than in androgen receptors-positive triple negative BC (TNBC). Absent androgen receptor expression confers a more aggressive QNBC course and correlates with the expression of cancer stem cell phenotype, COX-2, and basal markers such as CK5 and nestin. Basal-like phenotype is significantly associated with adverse prognostic markers including high KI-67, COX-2 expression, and cancer stem cell phenotype. Engrailed-1 expression is associated with unfavorable overall survival in QNBC patients. Non-coding ribonucleic acids play a significant role in BC tumourigenesis by virtue of their oncogenic and tumour-suppressive properties. The identification of QNBC-specific circulating microribonucleic acids may improve tumour detection and prognosis. There is an obvious necessity to intensify the problem-oriented interdisciplinary research on the hot topic of prognostic biomarkers of QNBC.

Recently, breast cancer (BC) continuously ranks first in the incidence rate of malignant neoplasms in womenworldwide. Quadruple negative BC (QNBC) is a recently identified subtype of triple negative BC (TNBC) presenting with negative androgen receptor expression. QNBC characterization and treatment is fraught with many challenges.There is cumulative evidence suggestingthat QNBC ishighly proliferative and immunogenic, rendering it anideal candidate for cytotoxic chemotherapy and immunotherapy. Several chemotherapeutic agents such as imatinib, cabozantinib, dasatinib, lucitanib,sunitinib, docetaxel, doxorubicin, and cyclophosphamidein QNBCpatients are highlighted. Some subtypes and related pathway proteins are preferentially expressed in QNBC and may act as effective therapeutic targets such as acyl-CoA synthetase4, S-phase kinase associated protein 2, immune checkpoint inhibitors, kinesin family member C1,and epidermal growth factor receptor. Several recent investigations comparing the therapeutic approach to QNBC and TNBC are briefly reviewed. Further more intensive and problem-oriented research in this topic of rising socio-medical importance is needed.

Recently, breast cancer (BC) continuously ranks first in the incidence rate of malignant neoplasms in women worldwide. Quadruple negative BC (QNBC) is a recently identified subtype of triple negative BC (TNBC) presenting with negative androgen receptor expression. QNBC characterization and treatment is fraught with many challenges. There is cumulative evidence suggesting that QNBC is highly proliferative and immunogenic, rendering it an ideal candidate for cytotoxic chemotherapy and immunotherapy. Several chemotherapeutic agents such as imatinib, cabozantinib, dasatinib, lucitanib, sunitinib, docetaxel, doxorubicin, and cyclophosphamide in QNBC patients are highlighted. Some subtypes and related pathway proteins are preferentially expressed in QNBC and may act as effective therapeutic targets such as acyl-CoA synthetase 4, S-phase kinase associated protein 2, immune checkpoint inhibitors, kinesin family member C1, and epidermal growth factor receptor. Several recent investigations comparing the therapeutic approach to QNBC and TNBC are briefly reviewed. Further more intensive and problem-oriented research in this topic of rising socio-medical importance is needed. [ABSTRACT FROM AUTHOR]

Quadruple-negative breast cancer (QNBC) presents with negative expression of estrogen, progesterone, and androgen receptors and of human epidermal growth factor receptor 2. This BC subtype has the worst prognosis. In QNBC, there is a greater paucity of prognostic biomarkers than in androgen receptors-positive triple negative BC (TNBC). Absent androgen receptor expression confers a more aggressive QNBC course and correlates with the expression of cancer stem cell phenotype, COX-2, and basal markers such as CK5 and nestin. Basal-like phenotype is significantly associated with adverse prognostic markers including high KI-67, COX-2 expression, and cancer stem cell phenotype. Engrailed-1 expression is associated with unfavorable overall survival in QNBC patients. Non-coding ribonucleic acids play a significant role in BC tumourigenesis by virtue of their oncogenic and tumour-suppressive properties. The identification of QNBC-specific circulating microribonucleic acids may improve tumour detection and prognosis. There is an obvious necessity to intensify the problem-oriented interdisciplinary research on the hot topic of prognostic biomarkers of QNBC. [ABSTRACT FROM AUTHOR]

We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1–3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013–7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS 6) and overall response rate (ORR) by RECIST 1.1 criteria. During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2–100%). The overall PFS 6 rate (as binary) was 22% (90% CI: 15.1–100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7–100%) and 38.5% (90% CI: 21.7%–100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. The study met its primary endpoint, with a PFS 6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients. • Enzalutamide was well-tolerated in AR+ recurrent ovarian cancer patients and demonstrated a suitable safety profile. • This study met its primary endpoint, as enzalutamide afforded modest progression-free survival. • The overall response rate to enzalutamide was low, with less than 2% of patients demonstrating radiographic response. • Further study of enzalutamide may be warranted, particularly in patients with AR+ low-grade serous ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract Introduction Although targeting human epidermal growth factor receptor 2 (HER2) is a meaningful treatment in HER2-positive breast cancer, ultimately resistance develops. Androgen receptor (AR) expression and immune cell infiltration are thought to be involved in trastuzumab response and may, therefore, be of interest as additional targets for therapy in HER2-positive breast cancer. Aim To improve insights into the presence among AR expression, immune cell infiltration and HER2, we analysed HER2-positive breast tumours. Methods Primary tumours of 221 patients treated with trastuzumab for metastatic disease were selected. HER2 status was centrally confirmed. AR, T-cells (CD3 and CD8), programmed cell death protein 1 (PD-1) and PD-1 ligand 1 immunohistochemical staining and M2 tumour-associated macrophages (TAMs; CD68 and CD163) immunofluorescence were performed. Tumour-infiltrating lymphocytes were evaluated by haematoxylin and eosin staining. Results Sufficient tumour material was available for 150 patients. Oestrogen receptor was expressed in 51.3% of the tumours and AR in 81.3% of the tumours. AR expression was inversely correlated with M2 TAM (Pearson's r = −0.361, P < 0.001), CD3+ (r = −0.199, P < 0.030) and CD8+ (r = −0.212, P < 0.021) T-cell infiltration. Clustering analysis showed high immune cell infiltration in AR low-expressing tumours, and low immune cell infiltration in AR-high expressing tumours. Conclusion AR expression inversely correlates with immune cell infiltration in HER2-positive breast cancer. Highlights • Androgen receptor (AR) expression was studied in human epidermal growth factor receptor 2–positive advanced breast cancer. • AR expression was negatively correlated with immune cell infiltration. • The strongest negative correlation with immune cell infiltration was with M2 tumour-associated macrophages. • A subgroup was identified with low immune cell infiltration and high AR expression. [ABSTRACT FROM AUTHOR]

Model of the our research was the adult male amphibian anura, Pelophylax bergeri, poikilotherm species not considered threatened by the IUCN, sampled in representative sites at different degree. In the first phase, a biochemical characterization of the ADP-ribosylation on the skin of barcoded amphibian anura collected from Matese Lake (clean reference site in CE, Italy) was carried out. Two PARP isoforms were evidence: the first of 66 kDa is localized into nucleus and activated by DNA damage; the second of 150 kDa is in cytoplasm, as demonstrated by biochemical and immunohistochemical analysis. Subsequently, the PARP activity, the quantitative expression of androgen receptor gene, and the levels of arsenic and chromium in skin and testis of frog and soil, water, and sediment collected from sites at different degrees of pollution were measured. A significant variation of PARP activity and androgen receptor expression levels was detected in both tissues of barcoded frogs from Sarno and Scafati, along Sarno River (SA, Italy), suggesting that a PARP activation is correlated to pollution and to steroid-regulated physiology disruption. [ABSTRACT FROM AUTHOR]

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