Genetic subtypes of invasive bladder cancer.

Purpose Of Review: Recently completed cancer genomics projects identified intrinsic subtypes in muscle-invasive bladder cancers. Here we will describe the studies that led to their discovery and review their biological and clinical properties.

Recent Findings: Whole genome mRNA expression profiling and unsupervised hierarchical cluster analyses identified intrinsic basal and luminal subtypes in muscle-invasive bladder cancers that are similar to the ones found in breast cancer.

Clinicopathologic significance and survival of TIP30 expression in laryngeal squamous cell carcinoma.

Background: The expression and clinical significance of TIP30 and p53 in laryngeal squamous cell carcinoma (LSCC) have not been investigated.

Method: We determined immunohistochemically the expression of TIP30 and p53 in surgical specimens from 105 patients with LSCC. Survivals were estimated using the Kaplan-Meier method.

Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model.

Purpose: To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy.

Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks.

Blinatumomab for the treatment of adult acute lymphoblastic leukemia.

The marker CD19 is frequently expressed on the surface of malignant B cells including non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL), which makes it an attractive target for antineoplastic therapy (1). T cells are part of the immune surveillance system for malignant cells (2). Blinatumomab is a bispecific T cell engager (BiTE(®)) antibody that binds both CD3-positive T cells and CD19-positive B cells via its two variable antigen-binding domains.

Statistical controversies in clinical research: scientific and ethical problems with adaptive randomization in comparative clinical trials.

Background: In recent years, various outcome adaptive randomization (AR) methods have been used to conduct comparative clinical trials. Rather than randomizing patients equally between treatments, outcome AR uses the accumulating data to unbalance the randomization probabilities in favor of the treatment arm that currently is superior empirically. This is motivated by the idea that, on average, more patients in the trial will be given the treatment that is truly superior, so AR is ethically more desirable than equal randomization.

Therapeutic opportunities in the intrinsic subtypes of muscle-invasive bladder cancer.

Recent studies revealed that muscle-invasive bladder cancers segregate into intrinsic basal and luminal subtypes that are similar to those described for breast cancer. Each subtype is enriched with potentially clinically actionable genomic alterations and epigenetic signatures; there are associations between tumor subtype and sensitivity to conventional cisplatin-based chemotherapy. The authors review biological and clinical characteristics of the intrinsic subtypes and describe their implications for the development of conventional and targeted agents.

Functional characterization of OPN in human laryngeal squamous cell carcinoma and its xenograft model in nude mice.

Background: Osteopontin (OPN) is involved in promotion of cancer cells by regulating various facets of tumor progression such as cell proliferation, angiogenesis and metastasis. To understand the role of OPN in laryngeal squamous cell carcinoma (LSCC), we thus explored the biological function of OPN in LSCC after silencing OPN expression by RNA interference (RNAi).

Method: The OPN expression in tumor tissues of LSCC was determined immunohistochemically in both LSCC and adjacent normal tissues.

Prognostic factors for outcome in patients with refractory and relapsed acute lymphocytic leukemia treated with inotuzumab ozogamicin, a CD22 monoclonal antibody.

Inotuzumab ozogamicin was found to be highly active in patients with refractory-relapsed acute lymphocytic leukemia (ALL), with an overall response rate of 58% and a median survival of 6.3 months. Identifying factors associated with different outcomes on inotuzumab therapy may help select patients for this treatment and advice of prognosis.

Distribution and timing of distant metastasis after local therapy in a large cohort of patients with esophageal and esophagogastric junction cancer.

Background: Patients with localized esophageal and esophagogastric junction cancer (EAC) receive chemoradiation and then surgery (trimodality, TMT) or definitive chemoradiation (bimodality, BMT). Distant metastases (DMs) are common but the details of their distribution and timing in a large cohort have not been described.

Methods: 629 patients with localized EAC who had TMT or BMT were analyzed.

A Bayesian Semi-parametric Approach for the Differential Analysis of Sequence Counts Data.

Data obtained using modern sequencing technologies are often summarized by recording the frequencies of observed sequences. Examples include the analysis of T cell counts in immunological research and studies of gene expression based on counts of RNA fragments. In both cases the items being counted are sequences, of proteins and base pairs, respectively.

Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high-dose cytarabine-based induction chemotherapy.

Outcomes of patients with acute myeloid leukemia (AML) who are refractory to high-dose Cytarabine (HiDAC)-based induction are dismal. Allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage may be effective and potentially superior to conventional salvage chemotherapy. Eighteen percent (285 of 1597) of AML patients were primary refractory to HiDAC-based regimens at the MD Anderson Cancer Center between 1995 and 2009.

Inhibition of inducible heat shock protein-70 (hsp72) enhances bortezomib-induced cell death in human bladder cancer cells.

The proteasome inhibitor bortezomib (Velcade) is a promising new agent for bladder cancer therapy, but inducible cytoprotective mechanisms may limit its potential efficacy. We used whole genome mRNA expression profiling to study the effects of bortezomib on stress-induced gene expression in a panel of human bladder cancer cell lines. Bortezomib induced strong upregulation of the inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A(high)) cells, but only induced the HSPA1B isoform in UM-UC10 and UM-UC13 (HSPA1A(low)) cells.

An English Translation of Joseph Luc Riopelle, MD, (Hôtel-Dieu of Montréal), and Jean Paul Thériault (Hôpital Général of Verdun, Québec, Canada): Sur une forme méconnue de sarcome des parties molles: le rhabdomyosarcome alvéolaire (concerning an unrecognized form of sarcoma of the soft tissues: alveolar rhabdomyosarcoma). annales d'anatomie pathologique 1956;1:88-111.

We believe that this is the first translation into English of the first description, in French, of a disease previously unknown. JL Riopelle and JP Thériault, both pathologists, reviewed clinical and pathologic findings in six young patients with soft tissue tumors, and contributed autopsy information on four of the patients. Only one patient was initially correctly diagnosed with rhabdomyosarcoma; the other five initially had alternative diagnoses.

HDAC inhibitor modulation of proteotoxicity as a therapeutic approach in cancer.

The strong clinical activity of the proteasome inhibitor bortezomib (Velcade) in multiple myeloma and other hematological malignancies has focused considerable attention on its mechanisms of action. Although NFκB inhibition was initially the mechanism in focus, accumulating evidence indicates that misfolded protein accumulation leading to proteotoxicity plays an even more important role in cell killing. Proteotoxicity that occurs as a consequence of protein aggregate accumulation has long been associated with the development of neurodegenerative diseases, and a large and growing body of literature has documented how protein aggregates are handled and disposed of via evolutionarily conserved mechanisms involving cross talk between the proteasome and autophagy in normal cells.

Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: a report from the Children's Oncology Group.

Background: We wanted to ascertain patterns of recurrence, re-treatment, and outcome among 188 eligible patients treated for localized orbital sarcoma on IRSG Protocols III/IV, 1984-1997.

Procedure: Retrospective chart review.

Results: Twenty-four of 188 patients (12.

Biological significance of HORMA domain containing protein 1 (HORMAD1) in epithelial ovarian carcinoma.

The present study was undertaken to determine the expression and biological significance of HORMAD1 in human epithelial ovarian carcinoma. We found that a substantial proportion of human epithelial ovarian cancers expressed HORMAD1. In vitro, HORMAD1 siRNA enhanced docetaxel induced apoptosis and substantially reduced the invasive and migratory potential of ovarian cancer cells (2774).

The chaplain as faithful companion: a response to King's case study.

This article is a response to a case study describing the spiritual care provided over an 18-month period by an experienced professional chaplain at a prominent cancer center to a woman undergoing stem cell transplantation following therapy for relapsed leukemia. The author, a professional chaplain at another cancer center, reviews the spiritual assessment, interventions, and outcomes presented by the attending chaplain. The author's comments are organized about the chaplain's characterization of the seven parts of the patient's spiritual profile: courage, meaning, psychological issues, courage and growth in facing spiritual/religious struggle, rituals, community, and authority.

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.

Objective: The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%.

A clinical perspective on genetic counseling and testing during end of life care for women with recurrent progressive ovarian cancer: opportunities and challenges.

10-15% of invasive epithelial ovarian cancer is attributable to hereditary breast and ovarian cancer. The identification of BRCA1/BRCA2 mutations in women with ovarian cancer allows for accurate predictive genetic testing of their at-risk relatives, who can then avail themselves of early detection and risk reduction strategies. In the case of women with recurrent progressive ovarian cancer, the window of opportunity for genetic testing can be particularly limited.

RNA interference in the clinic: challenges and future directions.

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. Although exploitation of RNAi has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release.

Unrelated donor transplantation for acute myelogenous leukemia in first remission.

We retrospectively analyzed the outcomes of all acute myelogenous leukemia (AML) patients in first remission (n = 44; median age = 48 years; high-risk cytogenetics = 59%) who received unrelated donor hematopoietic cell transplantation (HCT) with myeloablative conditioning regimen of i.v. busulfan, fludarabine, and antithymocyte globulin (ATG) between January 2002 and November 2009 at our institution.

Regulation of tumor angiogenesis by EZH2.

Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1).