Inhibition of Poly ADP-Ribose Glycohydrolase Sensitizes Ovarian Cancer Cells to Poly ADP-Ribose Polymerase Inhibitors and Platinum Agents.

Background: Poly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin.

The Molecular Basis of Gender Variations in Mortality Rates Associated With the Novel Coronavirus (COVID-19) Outbreak.

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact among different subpopulations. Emerging evidence from different parts of the world showed that male patients usually had a longer disease course as well as worse outcome compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for more effective and personalized response to this disease outbreak.

Identification of Predictive Biomarkers for Lymph Node Involvement in Obese Women With Endometrial Cancer.

Obesity, an established risk factor for endometrial cancer (EC), is also associated to increased risks of intraoperative and postoperative complications. A reliable tool to identify patients at low risk for lymph node (LN) metastasis may allow minimizing the surgical staging and omit lymphadenectomy in obese patients. To identify molecular biomarkers that could predict LN involvement in obese patients with EC we performed gene expression analysis in 549 EC patients using publicly available transcriptomic datasets.

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown.

The added value of sentinel node mapping in endometrial cancer.

Objective: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC).

Methods: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND.

Results: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND.

The impact of wait times on oncological outcome in high-risk patients with endometrial cancer.

Objective: To evaluate the impact of surgical wait times on outcome of patients with grade 3 endometrial cancer.

Methods: All consecutive patients surgically treated for grade 3 endometrial cancer between 2007 and 2015 were included. Patients were divided into two groups based on the time interval between endometrial biopsy and surgery: wait time from biopsy to surgery ≤12 weeks (84 days) vs more than 12 weeks.

Targeted sequencing of histologically defined serous endometrial cancer reflects prognosis and correlates with preoperative biopsy.

The aim of this study was to evaluate the impact of discordant endometrial sampling on the prognosis of patients finally diagnosed with uterine papillary serous carcinoma (UPSC) and to analyze UPSC mutational profile. Retrospective cohort study comparing outcomes of patients post-operatively diagnosed with UPSC and preoperatively diagnosed with endometrioid endometrial cancer (EEC) or UPSC. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 40 patients post-operatively diagnosed with UPSC, using next generation sequencing.

Biguanides in combination with olaparib limits tumorigenesis of drug-resistant ovarian cancer cells through inhibition of Snail.

Ovarian cancer is the most lethal gynecological malignancy. Currently, new chemotherapeutic strategies are required to improve patient outcome and survival. Biguanides, classic anti-diabetic drugs, have gained importance for theiri antitumor potency demonstrated by various studies.

Prolactin hormone exerts anti-tumorigenic effects in HER-2 overexpressing breast cancer cells through regulation of stemness.

Background: Breast cancers characterized by HER2 overexpression, belong to HER-2 enriched or luminal B subtypes, are frequently associated with higher incidence of tumor recurrence and therapeutic failure. These aggressive features have been attributed to the presence of cancer stem-like cell subpopulations known to have high tumor initiation, self -renewal capacities and high metastatic potential. Depleting these stem-like cells in these tumors therefore might help in improving therapeutic response and patient outcome.

Risk factors for lymph nodes involvement in obese women with endometrial carcinomas.

Objective: To assess risk factors for lymph node involvement in patients with endometrial cancer and a body-mass index (BMI) ≥30 kg/m.

Materials And Methods: A retrospective analysis was performed of obese patients diagnosed with endometrial carcinoma between 2007 and 2015, treated in a single center in Montreal. Preoperative variables evaluated were age, BMI, parity, and preoperative ASA score, grade, CA-125 and histology.

Concomitant Expression of Prolactin Receptor and TGFβ Receptors in Breast Cancer: Association with Less Aggressive Phenotype and Favorable Patient Outcome.

The epithelial-mesenchymal transition (EMT) process is known to play an essential role in tumor progression, metastasis and resistance to therapy. This report evaluated the prognostic value of co-expression of the receptor for prolactin (PRLR), a suppressor of EMT, and the receptors for transforming growth factor β (TGFβRI and TGFβRII), an inducer of EMT, in association with different clinicopathological parameters using TMA of 102 breast cancer patients and publicly available data on breast cancer patients. Interestingly, the results revealed that malignant tissues had significantly lower levels of concomitant protein expression of these receptors in comparison to normal/benign breast tissue.

Nucleostemin expression in breast cancer is a marker of more aggressive phenotype and unfavorable patients' outcome: A STROBE-compliant article.

Cancer stem cells (CSCs) are postulated to play significant role in the pathogenesis, progression as well as drug resistance of breast cancer. Nucleostemin (NS) is thought to be a key molecule for stemness, and the clinical impact of NS immunoreactivity in breast cancer can indicate its actual role and future therapeutic potentials.The current study is an observational study with an attempt to evaluate the correlation between NS expression (protein and gene expression levels) and different clinicopathological attributes of invasive breast cancer.

Prolactin modulates TNBC aggressive phenotype limiting tumorigenesis.

Triple-negative breast cancer (TNBC) accounts for ~20% of all breast cancer cases. The management of TNBC represents a challenge due to its aggressive phenotype, heterogeneity and lack of targeted therapy. Loss of cell differentiation and enrichment with breast cancer stem-like cells (BCSC) are features of TNBC contributing to its aggressive nature.

Sequential therapeutic targeting of ovarian Cancer harboring dysfunctional BRCA1.

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become the first targeted therapies available in the treatment of patients with high-grade serous ovarian cancer (HGSOC). We recently described a significant reduction in PARP1 protein levels in vitro and in vivo in patients treated with standard carboplatinum-paclitaxel chemotherapy, raising the question whether the sequence of treatment used today with chemotherapy followed by PARPi is optimal. In this study, we aim to evaluate if the sequence of PARPi followed by chemotherapy could be more beneficial.

A dual prognostic role for the TGFβ receptors in human breast cancer.

The transforming growth factor-β (TGFβ) plays a dual role in breast cancer, acting as a tumor suppressor in early carcinomas while promoting tumor metastasis in more advanced breast carcinoma. As a result, the prognostic role of TGFβ and its signaling components in breast cancer remains unclear. Here we evaluated the expression levels of TGFβ signaling receptors TβRII and TβRI using human breast cancer tissue microarrays and a large publicly available gene profiling database in relation to various clinicopathological parameters.

Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy.

Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases.