Dual-drug loaded micelle for combinatorial therapy targeting HIF and mTOR signaling pathways for ovarian cancer treatment.

Mutations in the tumor protein (TP53) and the mammalian target of rapamycin (mTOR) pathway have been elucidated as driver mutations in ovarian carcinomas that transform into an invasive phenotype under hypoxic conditions. Chetomin (CHE) targets the hypoxic pathway while Everolimus (EVR) acts on the mTOR pathway. Poor aqueous solubilities of both compounds limit their clinical applications.

Natural Product Target Network Reveals Potential for Cancer Combination Therapies.

A body of research demonstrates examples of and synergy between natural products and anti-neoplastic drugs for some cancers. However, the underlying biological mechanisms are still elusive. To better understand biological entities targeted by natural products and therefore provide rational evidence for future novel combination therapies for cancer treatment, we assess the targetable space of natural products using public domain compound-target information.

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA).

Background: In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile.

Correction: Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours.

The additional information of this manuscript originally stated that the authors declare no competing interests. This statement was incorrect, and should instead have stated the following:M.C.

Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours.

Background: Most patients with KIT-mutant gastrointestinal stromal tumours (GISTs) benefit from imatinib, but treatment resistance results from outgrowth of heterogeneous subclones with KIT secondary mutations. Once resistance emerges, targeting KIT with tyrosine kinase inhibitors (TKIs) sunitinib and regorafenib provides clinical benefit, albeit of limited duration.

Methods: We systematically explored GIST resistance mechanisms to KIT-inhibitor TKIs that are either approved or under investigation in clinical trials: the studies draw upon GIST models and clinical trial correlative science.

Publisher Correction: Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy.

The original version of this Article contained errors in Fig. 7. In panels e and f, the graph titles incorrectly read 'LNCaP-AdtNs' and 'LAPC4-AdtNs', respectively.

Recycling Discarded Drugs: Improving Access to Oral Antineoplastic Drugs.

It is common for patients to have limited access to oral antineoplastics or to discontinue treatment because of cost. Such oral treatments are also discontinued because of toxicity, disease progression, or death, resulting in unused portions of these medications. Policies for the subsequent use or destruction of unused drugs exist, but none completely address the need for methods of recycling back to the patients in need.

Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy.

Despite recent advances, the efficacy of androgen/androgen receptor (AR)-targeted therapy remains  limited for many patients with metastatic prostate cancer. This is in part because prostate cancers adaptively switch to the androgen/AR-independent pathway for survival and growth, thereby conferring therapy resistance. Tumor hypoxia is considered as a major cause of treatment resistance.

Radiotherapy for Hepatocellular Carcinoma in Russia: a Survey-Based Analysis of Current Practice and the Impact of an Educational Workshop on Clinical Expertise.

Radiation therapy (RT) is an effective treatment modality for hepatocellular carcinoma (HCC), but globally, it is underutilized. In Russia, practice patterns with regard to liver-directed radiation are unknown. Under the auspices of Russian Society of Clinical Oncology (RUSSCO), our team conducted an IRB-approved contouring workshop for Russian radiation oncologists.

SUMO protease SENP1 deSUMOylates and stabilizes c-Myc.

Posttranslational modifications play a crucial role in the proper control of c-Myc protein stability and activity. c-Myc can be modified by small ubiquitin-like modifier (SUMO). However, how SUMOylation regulates c-Myc stability and activity remains to be elucidated.

Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in Castration-Resistant Prostate Cancer.

Purpose: This study assesses the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model and the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2LAARx).

Patients And Methods: The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and on the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial had a 3 × 3 panobinostat dose-escalation design.

Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer.

Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide.

Patients And Methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets.

Network-Based Predictors of Progression in Head and Neck Squamous Cell Carcinoma.

The heterogeneity in head and neck squamous cell carcinoma (HNSCC) has made reliable stratification extremely challenging. Behavioral risk factors such as smoking and alcohol consumption contribute to this heterogeneity. To help elucidate potential mechanisms of progression in HNSCC, we focused on elucidating patterns of gene interactions associated with tumor progression.

A New Framework for Patient Engagement in Cancer Clinical Trials Cooperative Group Studies.

For the past two decades, the National Cancer Institute (NCI) has supported the involvement of patient advocates in both internal advisory activities and funded research projects to provide a patient perspective. Implementation of the inclusion of patient advocates has varied considerably, with inconsistent involvement of patient advocates in key phases of research such as concept development. Despite this, there is agreement that patient advocates have improved the patient focus of many cancer research studies.

Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy.

Background: Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki-67 proliferative index. Single-center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy.

Methods: The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL.

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

Importance: Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients.

Objective: To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS.

Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene.

Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha () gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein-ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes.

Extracellular vesicles in the hematopoietic microenvironment.

Self-renewal and differentiation are defining characteristics of hematopoietic stem and progenitor cells, and their balanced regulation is central to lifelong function of both blood and immune systems. In addition to cell-intrinsic programs, hematopoietic stem and progenitor cell fate decisions are subject to extrinsic cues from within the bone marrow microenvironment and systemically. Yet, many of the paracrine and endocrine mediators that shape hematopoietic function remain to be discovered.

10-Year Study of Christian Church Support for Domestic Violence Victims: 2005-2015.

Purpose: This 10 -year study explored the climate of support for victims of domestic violence among Christian clergy and church members between 2005 and 2015.

Method: Using a convenience sample, surveys were sent out to congregations in the Upper Midwest in 2005 and 2015. The survey included demographics; two items measuring perception of domestic violence in the congregation andcommunity; six Likert Scale items regarding agreement with statements concerning leaving an abusive marriage; four 'Yes-No' items regarding the impact of faith in leaving, support of the congregation, community resources,and clergy as counselors.

microRNA-130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO-1.

FOSL1 is frequently overexpressed in multiple types of human cancers including invasive breast cancers and implicated in cancer invasion and metastasis. However, how FOSL1 is overexpressed in cancers remains to be elucidated. Several microRNAs (miRNAs) have been shown to target FOSL1 and are downregulated in human cancers.

CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion.

The functional significance of the chemokine receptor CCR5 in human breast cancer epithelial cells is poorly understood. Here, we report that CCR5 expression in human breast cancer correlates with poor outcome. CCR5 breast cancer epithelial cells formed mammospheres and initiated tumors with >60-fold greater efficiency in mice.

The ubiquitin-specific protease USP36 is a conserved histone H2B deubiquitinase.

Histone H2B monoubiquitination plays a critical role in the regulation of gene transcription. Deregulation of H2B monoubiquitination contributes to human pathologies, such as cancer. Here we report that human USP36 is a novel H2Bub1 deubiquitinase.