Positive experience of intraperitoneal chemotherapy followed by intravenous chemotherapy in heavily pretreated patients with suboptimal residual ovarian cancer and primary peritoneal cancer.

Aims And Background: To assess feasibility and toxicity of intraperitoneal administration of cisplatin and paclitaxel, followed by intravenous chemotherapy in pretreated patients with suboptimal ovarian cancer (residuum >1 cm) or primary peritoneal tumor, and suffering from ascites and/or intestinal obstruction.

Methods: Fourteen relapsed ovarian cancer patients, 5 of whom were platinum sensitive (platinum-free interval >6 mo), 7 platinum-resistant (platinum-free interval <6 mo), and 2 platinum-refractory, received one cycle of intraperitoneal cisplatin, 100 mg/m2 on day 1, and two cycles of intraperitoneal paclitaxel, 120 mg/m2 on days 8 and 14. Intravenous chemotherapy was administrated 4 weeks following the last intraperitoneal paclitaxel instillation.

PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression.

This study addresses the role of PTEN loss in intrinsic resistance to the BRAF inhibitor PLX4720. Immunohistochemical staining of a tissue array covering all stages of melanocytic neoplasia (n = 192) revealed PTEN expression to be lost in >10% of all melanoma cases. Although PTEN expression status did not predict for sensitivity to the growth inhibitory effects of PLX4720, it was predictive for apoptosis, with only limited cell death observed in melanomas lacking PTEN expression (PTEN-).

Clinical experience and critical evaluation of the role of sorafenib in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common malignancy worldwide with approximately 95,000 new cases per year and ranks as the sixth cause of cancer deaths. Until recently, the slightly active and very toxic cytokines were available for patients with advanced RCC. Advances have been made in understanding the molecular biology of renal cancer.

Bevacizumab and glioblastomas, a single-centre experience: how disease history and characteristics may affect clinical outcome.

Background: In 2009, bevacizumab, a monoclonal antibody to vascular endothelial growth factor, received accelerated approval by the United States Food and Drug Administration for the treatment of glioblastoma, based on its high response rate (RR) and 6-month progression-free survival (PFS-6). However, time to progression and overall survival (OS) were disappointing. Since 2008 have been data collected evaluating the safety and efficacy of bevacizumab in patients with relapsed malignant gliomas.

Tolerability of PLD/oxaliplatin regimen in recurrent ovarian cancer patients with previous fragility to carboplatin/paclitaxel treatment.

Objectives: This retrospective analysis aims at describing the safety profile of treatment with pegylated liposomal doxorubicin (PLD) and oxaliplatin in recurrent ovarian cancer patients who experienced myelotoxicity (principally neutropenia) during first line chemotherapy with carboplatin and paclitaxel.

Methods: We reviewed the medical records of patients with relapsed ovarian cancer treated with PLD/Oxaliplatin at the Istituto Oncologico Veneto (IOV)/IRCCS, Padua University between 2002 and 2008.

Results: A cohort of 16 patients who developed myelodepression and other toxicities of grade 3 to grade 4 during first line chemotherapy with carboplatin/paclitaxel, were selected for this retrospective study.

An update on targeted therapy in metastatic renal cell carcinoma.

An improved understanding of the biological pathways deregulated in renal cell carcinoma has led to the development of various targeted agents, changing dramatically the therapeutic options for this disease. However, despite numerous opinions and guidelines, the optimal treatment still remains uncertain. In this review, we analyze the most recent published reports regarding the agents sunitinib, bevacizumab, sorafenib, temsirolimus, and everolimus.

Multimodal assessment of protein functional deficiency supports pathogenicity of BRCA1 p.V1688del.

Unequivocal discrimination between neutral variants and deleterious mutations is crucial for appropriate counseling of individuals with a BRCA1 or BRCA2 sequence change. An increasing number of variants of uncertain significance (VUS) are being identified, the unclassified biological effect of which poses clinical concerns. A multifactorial likelihood-based approach recently suggested disease causality for BRCA1 p.

Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas.

Recent studies have shown that there is a considerable heterogeneity in the response of melanoma cell lines to MEK and BRAF inhibitors. In the current study, we address whether dysregulation of cyclin-dependent kinase 4 (CDK4) and/or cyclin D1 contribute to the BRAF inhibitor resistance of melanoma cells. Mutational screening identified a panel of melanoma cell lines that harbored both a BRAF V600E mutation and a CDK4 mutation: K22Q (1205Lu), R24C (WM39, WM46, and SK-Mel-28), and R24L (WM902B).

The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families.

The demand for BRCA1 and BRCA2 mutation screening is increasing as their identification will affect medical management. However, both the contribution of different mutation types in BRCA1 and BRCA2 and whom should be offered testing for large genomic rearrangements have not been well established in the U.S.

Large genomic rearrangement in BRCA1 and BRCA2 and clinical characteristics of men with breast cancer in the United States.

Purpose: Male breast cancer has been linked extensively to mutations of BRCA2 and, to a lesser extent, BRCA1. The aim of this study was to perform a comprehensive analysis of point mutations and genomic rearrangements in the BRCA1 and BRCA2 genes in 41 men with breast cancer.

Patients And Methods: Deleterious point mutations were identified in 15 men (37%): 4 (10%) and 11 (27%) in BRCA1 and BRCA2, respectively.

Establishment and characterization of xenografts and cancer cell cultures derived from BRCA1 -/- epithelial ovarian cancers.

The BRCA1 gene is responsible for a high number of hereditary breast and ovarian cancers that cluster in families with a strong genetic predisposition. Despite intense investigation, the accumulating findings on BRCA1 biological functions have not yet been translated into specific therapeutic approaches, also due to the lack of suitable experimental models. The purpose of this study was to establish and characterize cell cultures and xenografts from patients with BRCA1 -/- ovarian cancers.

Prevalence of BRCA1 genomic rearrangements in a large cohort of Italian breast and breast/ovarian cancer families without detectable BRCA1 and BRCA2 point mutations.

The presence of genomic rearrangements of the BRCA1 gene in breast and/or ovarian cancer families has been intensively investigated in patients from various countries over the last years. A number of different rearrangements have been reported by several studies that clearly document the involvement of this mutation type in genetic predisposition to breast and ovarian cancer. Population-specific studies are now needed to evaluate the prevalence of genomic rearrangements before deciding whether to include ad hoc screening procedures into standard diagnostic mutation detection approaches.

Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families.

The recent identification of major genomic rearrangements in breast and breast/ovarian cancer families has widened the mutational spectrum of the BRCA1 gene, thus increasing the number of informative patients who can benefit from molecular screening. Numerous types of alterations have been identified in different populations with variable frequencies, probably due to both ethnic diversity and the technical approach employed. In fact, although several methods have been successfully used to detect large genomic deletions and insertions, most are laborious, time-consuming, and of variable sensitivity.