Inguinal bladder hernia: differentials for a male groin mass.

Inguinal bladder hernia (IBH) is an uncommon occurrence in males with a groin mass. It may be present with lower urinary tract symptoms but is often asymptomatic, making it a diagnostic challenge. IBH is frequently an incidental finding during surgery, which increases the risk of iatrogenic injury of the bladder. This report examines the case of a 77-year-old male who experienced a painful, reducible right-sided groin mass with acute urinary retention. Investigations conducted through computed tomography exhibited a right indirect inguinal hernia containing omental fat and a portion of the urinary bladder. The patient underwent a right open herniorrhaphy with mesh repair. This report presents a systematic approach to differential diagnoses for a male groin mass and its relationship to IBH.

Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma.

Despite the addition of several new agents to the armamentarium for the treatment of multiple myeloma (MM) in the last decade and improvements in outcomes, the refractory and relapsing disease continues to take a great toll, limiting overall survival. Therefore, additional novel approaches are needed to improve outcomes for MM patients. The oncogenic transcription factor MYC drives cell growth, differentiation and tumor development in many cancers. MYC protein levels are tightly regulated by the proteasome and an increase in MYC protein expression is found in more than 70% of all human cancers, including MM. In addition to the ubiquitin-dependent degradation of MYC by the 26S proteasome, MYC levels are also regulated in a ubiquitin-independent manner through the REGγ activation of the 20S proteasome. Here, we demonstrate that a small molecule activator of the 20S proteasome, TCH-165, decreases MYC protein levels, in a manner that parallels REGγ protein-mediated MYC degradation. TCH-165 enhances MYC degradation and reduces cancer cell growth in vitro and in vivo models of multiple myeloma by enhancing apoptotic signaling, as assessed by targeted gene expression analysis of cancer pathways. Furthermore, 20S proteasome enhancement is well tolerated in mice and dogs. These data support the therapeutic potential of small molecule-driven 20S proteasome activation for the treatments of MYC-driven cancers, especially MM.

Studying Lymphatic Metastasis in Breast Cancer: Current Models, Strategies, and Clinical Perspectives.

Breast cancer is the most commonly diagnosed cancer in women and the second most common cause of cancer-related deaths in the United States. Although early detection has significantly decreased breast cancer mortality, patients diagnosed with distant metastasis still have a very poor prognosis. The most common site that breast cancer spreads to are local lymph nodes. Therefore, the presence of lymph node metastasis remains one of most important prognostic factors in breast cancer patients. Given its significant clinical implications, increased efforts have been dedicated to better understand the molecular mechanism governing lymph node metastasis in breast cancer. The identification of lymphatic-specific biomarkers, including podoplanin and LYVE-1, has propelled the field of lymphatic metastasis forward. In addition, several animal models such as cell line-derived xenografts, patient-derived xenografts, and spontaneous tumor models have been developed to recreate the process of lymphatic metastasis. Moreover, the incorporation of various -omic platforms have provided further insight into the genetic drivers facilitating lymphatic metastasis, as well as potential biomarkers and therapeutic targets. Here, we highlight various models of lymphatic metastasis, their potential pitfalls, and other tools available to study lymphatic metastasis including imaging modalities and -omic studies.

Bilateral breast masses as a presentation for T-cell acute lymphoblastic leukaemia.

Here we describe a 27-year-old woman, 5 months post partum, who presented to the emergency department with bilateral breast masses. She was initially treated as lactational mastitis with no improvement. Breast ultrasound showed bilateral breast and axillary lymphadenopathy suggestive of metastatic/neoplastic process, and chest X-ray showed a large anterior mediastinal mass. Further work-up led to the diagnosis of T-cell acute lymphoblastic leukaemia. The patient was started on a paediatric regimen using the children's oncology group AALL0434 protocol. The patient achieved a complete remission following induction chemotherapy with resolution of her presenting symptoms.

Impact of BRCA Mutation Status on Survival of Women With Triple-negative Breast Cancer.

INTRODUCTION: The effect of germline BRCA mutations on the outcomes of patients with triple-negative breast cancer (TNBC) is not well understood. MATERIALS AND METHODS: The present retrospective study included women with newly diagnosed TNBC from January 1, 2004 to December 30, 2013. The demographic and tumor characteristics, genetic testing results, and outcomes were collected by a review of the patients' medical records. The outcomes were compared between the BRCA+ and BRCA- women. Kaplan-Meier curves were plotted for survival analysis, and Cox proportional hazard regression was used to determine the predictors of recurrence-free survival. RESULTS: A total of 266 TNBC patients who had undergone BRCA testing were included in the final analysis. Of the 266 patients, 72 (27.0%) tested positive for a pathogenic BRCA mutation and 194 (73.0%) tested negative. BRCA+ women were more likely to be diagnosed with breast cancer at a younger age than were the BRCA- women. Mutation carriers were also more likely to undergo bilateral mastectomy and less likely to receive radiation. The 2- and 5-year overall survival in BRCA+ women was 97.1% and 83.1% and was 97.3% and 89.7% in the BRCA- women, respectively. No statistically significant difference was found in overall survival between the BRCA+ and BRCA- group. No statistically significant difference was noted in the rate of locoregional recurrence, distant recurrence, or recurrence-free survival between the BRCA+ and BRCA- women. CONCLUSION: Our study has demonstrated that BRCA mutation carrier status does not affect overall survival or recurrence-free survival in patients with TNBC.

The extracytoplasmic adaptor protein CpxP is degraded with substrate by DegP.

In Escherichia coli, the CpxR/A two-component system senses various types of extracytoplasmic stresses and responds by activating the expression of genes encoding periplasmic protein folding and trafficking factors that clear such stresses to ensure the organism's survival. The cpxP gene encodes a small, stress-combative periplasmic protein and is the most strongly induced member of the Cpx regulon. We demonstrate that the Cpx stress response suppresses the toxicity associated with two misfolded proteins derived from the P pilus of uropathogenic E. coli and that mutations in either cpxP or the gene for the periplasmic protease DegP prevent suppression by preventing the degradation of these proteins. Strikingly, the presence of a periplasmic misfolded protein substrate significantly enhances the proteolysis of CpxP by DegP. Our data suggest that CpxP functions as a periplasmic adaptor protein that is required for the effective proteolysis of a subset of misfolded substrates by the DegP protease.