Efficacy of Split Schedule Versus Conventional Schedule Neoadjuvant Cisplatin-Based Chemotherapy for Muscle-Invasive Bladder Cancer.

Neoadjuvant cisplatin-based chemotherapy (NAC; 70 mg/m) is standard of care for muscle-invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m on day 1 + 8 or 1 + 2 (i.e.

Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes.

Background: The authors evaluated mocetinostat (a class I/IV histone deacetylase inhibitor) in patients with urothelial carcinoma harboring inactivating mutations or deletions in CREB binding protein [CREBBP] and/or E1A binding protein p300 [EP300] histone acetyltransferase genes in a single-arm, open-label phase 2 study.

Methods: Eligible patients with platinum-treated, advanced/metastatic disease received oral mocetinostat (at a dose of 70 mg 3 times per week [TIW] escalating to 90 mg TIW) in 28-day cycles in a 3-stage study (ClinicalTrials.gov identifier NCT02236195).

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2).

Background: A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy.

Methods: Multicentre, phase II study with 1:1 randomisation to apatorsen (three loading doses at 600 mg intravenous followed by weekly doses) plus docetaxel (75 mg/m intravenous every 21 days) (A/D) or docetaxel alone. Overall survival (OS) was the primary end point with a P value <0.

Recruited T cells promote the bladder cancer metastasis via up-regulation of the estrogen receptor β/IL-1/c-MET signals.

Clinical data indicates that T cells can be recruited to bladder cancer (BCa), yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4 T cells than did normal bladder cells.

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study.

Objective: To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).

Patients And Methods: RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France.

Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

Background: Platinum (Pt)-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC). However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance.

Expression Levels of DNA Damage Repair Proteins Are Associated With Overall Survival in Platinum-Treated Advanced Urothelial Carcinoma.

Background: Combination platinum chemotherapy is standard first-line therapy for metastatic urothelial carcinoma (mUC). Defining the platinum response biomarkers for patients with mUC could establish personalize medicine and provide insights into mUC biology. Although DNA repair mechanisms have been hypothesized to mediate the platinum response, we sought to analyze whether increased expression of DNA damage genes would correlate with worse overall survival (OS) in patients with mUC.

Bladder cancer in the elderly patient: challenges and solutions.

Bladder cancer (BC) is an age-associated malignancy with increased prevalence in the elderly population. Elderly patients are a vulnerable population at increased risk for treatment-related toxicity secondary to medical comorbidities and geriatric syndromes. As a result, this population has been historically undertreated and suffers worse disease-specific outcomes than younger patients with BC.

HER2 as a target in invasive urothelial carcinoma.

We evaluated primary tumors from two cohorts, Spain (N = 111) and Greece (N = 102), for patients who were treated with platinum-based chemotherapy. Patients were tested for HER2 status (IHC score of 3+ or FISH ratio of ≥ 2.2) by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), DNA copy number, mRNA expression, and mutation status in patients with metastatic urothelial carcinoma (UC), and its impact on survival.

The role of genomics in the management of advanced bladder cancer.

Advanced bladder cancer (ABC) is an aggressive malignancy with a poor prognosis. For the last 30 years, the standard of care for this disease has consisted of combination chemotherapy with a platinum-containing regimen as first-line therapy. Cisplatin is the most active cytotoxic agent against bladder cancer, but because of competing comorbidities, many patients are ineligible for this agent and instead receive carboplatin.

Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo.

Clinical reports show males have a higher bladder cancer (BCa) incidence than females. The sexual difference of BCa occurrence suggests that estrogen and its receptors may affect BCa development. Estrogen receptor alpha (ERα) is the classic receptor to convey estrogen signaling, however, the function of ERα in BCa development remains largely unknown.

Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma.

Unlabelled: Cisplatin-based chemotherapy is the standard of care for patients with muscle-invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, although molecular determinants of cisplatin response are incompletely understood. We performed whole-exome sequencing on pretreatment tumor and germline DNA from 50 patients with muscle-invasive urothelial carcinoma who received neoadjuvant cisplatin-based chemotherapy followed by cystectomy (25 pT0/pTis "responders," 25 pT2+ "nonresponders") to identify somatic mutations that occurred preferentially in responders.

Integrative analysis of 1q23.3 copy-number gain in metastatic urothelial carcinoma.

Purpose: Metastatic urothelial carcinoma of the bladder is associated with multiple somatic copy-number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy.

Experimental Design: We obtained overall survival (OS) and array DNA copy-number data from patients with metastatic urothelial carcinoma in two cohorts.

The evolving understanding of microRNA in bladder cancer.

Purpose: Micro ribonucleic acid (miR) expression is altered in urologic malignancies, including bladder cancer (BC). Individual miRs have been shown to modulate multiple signaling pathways that contribute to BC. We reviewed the primary literature on the role of miRs in BC; we provide a general introduction to the processing, regulation, and function of miRs as tumor suppressors and oncogenes and critically evaluate the literature on the implications of altered miR expression in BC.

Update in Urothelial Carcinoma: Novel Agents and Targeted Therapy.

Urothelial carcinoma (UC) is a chemosensitive disease with high response rates to platinum-based combination chemotherapy in locally advanced or advanced disease. However, de novo or emergence of cisplatin-resistance limits the duration of response, patients are frequently ineligible for cisplatin, and therapies tested thus far have minimal activity as second-line therapy. The first wave of clinical trials of novel agents and targeted therapy have modestly advanced the field and laid the foundations for future studies.

Personalized therapy for urothelial cancer: review of the clinical evidence.

Despite a detailed understanding of the molecular aberrations driving the development of urothelial cancers, this knowledge has not translated into advances for the treatment of this disease. Urothelial cancers are chemosensitive, and platinum-based combination chemotherapy remains the standard of care for advanced disease, as well as neoadjuvant and adjuvant therapy for locally advanced disease. However, nearly half of patients who undergo resection of locally advanced urothelial cancer will relapse and eventually develop platinum-resistant disease.

Genomic and phenotypic analysis reveals a key role for CCN1 (CYR61) in BAG3-modulated adhesion and invasion.

Chaperone protein quantity may regulate the balance of proteins involved in invasion and malignancy. BAG3 is a co-chaperone and pro-survival protein that has been implicated in adhesion, migration, and metastasis. We reported that BAG3 overexpression in MDA435 human breast cancer cells results in a significant decrease in migration and adhesion to matrix molecules that is reversed upon deletion of the BAG3 proline-rich domain (dPXXP).

CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins.

CAIR-1/BAG-3 is a stress and survival protein that has been shown to bind SH3 domain-containing proteins through its proline-rich (PXXP) domain. Because stress and survival pathways are active during invasion and metastasis, we hypothesized that CAIR-1 is a regulator of signaling pathways that modulate cell adhesion and migration. MDA-435 human breast carcinoma cells were stably transfected with full-length CAIR-1 (FL) or a proline-rich domain deleted mutant (dPXXP).

The "gender gap" in authorship of academic medical literature--a 35-year perspective.

Background: Participation of women in the medical profession has increased during the past four decades, but issues of concern persist regarding disparities between the sexes in academic medicine. Advancement is largely driven by peer-reviewed original research, so we sought to determine the representation of female physician-investigators among the authors of selected publications during the past 35 years.

Methods: Original articles from six prominent medical journals--the New England Journal of Medicine (NEJM), the Journal of the American Medical Association (JAMA), the Annals of Internal Medicine (Ann Intern Med), the Annals of Surgery (Ann Surg), Obstetrics & Gynecology (Obstet Gynecol), and the Journal of Pediatrics (J Pediatr)--were categorized according to the sex of both the first and the senior (last listed) author.

The role of proteomics in the diagnosis and treatment of ovarian cancer.

Ovarian cancer is the leading cause of gynecologic cancer death in the Western world and more than 70% of patients are diagnosed with advanced stage disease. The high mortality rate is due to the difficulty in the early detection of ovarian cancer. Current screening strategies lack the necessary sensitivity and specificity to reliably and accurately diagnose affected women, prompting investigators to seek alternative means of analysis found in protein pathways and networks.