Mitral valvular surgery outcomes in a centre with a dedicated mitral multi-disciplinary team.

International guidelines recommend 'heart teams' as the preferred method for decision-making. Heart team processes, mandatory attendees and investigations vary significantly between hospitals. We assessed outcomes following mitral valvular surgery in a tertiary referral centre with a dedicated mitral multi-disciplinary team (MDT).

A rare presentation of mycotic cerebral aneurysm, subarachnoid haemorrhage, and mitral valve aneurysm in left-sided lnfective endocarditis: a case report and literature review.

Background: Infective endocarditis (IE) can present as a syndromic-like condition with multisystem involvement; this can make early diagnosis particularly challenging. Rarely, left-sided IE can lead to mitral valve aneurysm formation. Showering of septic emboli to the cerebral circulation may result in a mycotic aneurysm that can rupture, leading to haemorrhagic stroke, as in this case.

Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC.

Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC).

Saracatinib synergizes with enzalutamide to downregulate androgen receptor activity in castration resistant prostate cancer.

Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC).

Massively parallel, computationally guided design of a proenzyme.

Confining the activity of a designed protein to a specific microenvironment would have broad-ranging applications, such as enabling cell type-specific therapeutic action by enzymes while avoiding off-target effects. While many natural enzymes are synthesized as inactive zymogens that can be activated by proteolysis, it has been challenging to redesign any chosen enzyme to be similarly stimulus responsive. Here, we develop a massively parallel computational design, screening, and next-generation sequencing-based approach for proenzyme design.

Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma.

The lack of effective treatment options for advanced non-clear cell renal cell carcinoma (NCCRCC) is a critical unmet clinical need. Applying a high-throughput drug screen to multiple human kidney cancer cells, we identify the combination of the VEGFR-MET inhibitor cabozantinib and the SRC inhibitor dasatinib acts synergistically in cells to markedly reduce cell viability. Importantly, the combination is well tolerated and causes tumor regression .

Bioengineering Novel Chimeric microRNA-34a for Prodrug Cancer Therapy: High-Yield Expression and Purification, and Structural and Functional Characterization.

Development of anticancer treatments based on microRNA (miRNA/miR) such as miR-34a replacement therapy is limited to the use of synthetic RNAs with artificial modifications. Herein, we present a new approach to a high-yield and large-scale biosynthesis, in Escherichia coli using transfer RNA (tRNA) scaffold, of chimeric miR-34a agent, which may act as a prodrug for anticancer therapy. The recombinant tRNA fusion pre-miR-34a (tRNA/mir-34a) was quickly purified to a high degree of homogeneity (>98%) using anion-exchange fast protein liquid chromatography, whose primary sequence and post-transcriptional modifications were directly characterized by mass spectrometric analyses.

Manubrium-limited sternotomy decreases blood loss after aortic valve replacement surgery.

Objectives: Minimally invasive surgical approaches for aortic valve replacement (AVR) are growing in popularity in an attempt to decrease morbidity from conventional surgery. We have adopted a technique that divides only the manubrium and spares the body of the sternum. We sought to determine whether patients benefit from this less-invasive approach.

Antimicrobial regime for cardiac surgery: the safety and effectiveness of short-course flucloxacillin (or teicoplanin) and gentamicin-based prophylaxis.

Objectives: To determine if changing from multidose cefuroxime-based to flucloxacillin (or teicoplanin) and gentamicin-based antibiotic prophylaxis for cardiac surgery was as effective at preventing infections without increasing postoperative renal impairment.

Methods: Outcomes in consecutive patients from two 18-month periods with the different antibiotic regimes. Group 1 (1725 patients)-cefuroxime 1.

Tumor-targeting multifunctional micelles for imaging and chemotherapy of advanced bladder cancer.

Aim: This work aimed to determine if the treatment outcomes of bladder cancer could be improved by targeting micelles that are decorated with bladder cancer-specific ligands on the surface and loaded with the chemotherapeutic drug paclitaxel.

Materials & Methods: Targeting efficacy and specificity was determined with cell lines. An in vivo targeting and anti-tumor efficacy study was conducted in mice carrying patient-derived xenografts.

Stem-like cells in bladder cancer cell lines with differential sensitivity to cisplatin.

Background: Recurrence is a common problem in bladder cancer; this has been attributed to cancer stem cells. In this study, we characterized potential cancer stem cell populations isolated from three cell lines that demonstrate different responses to cisplatin.

Materials And Methods: The ALDEFLUOR® assay was used to isolate cells from TCCSUP, T24, and 5637 cell lines, and these cells were evaluated for their ability to form colonies, differentiate, migrate and invade.

miR-125b promotes growth of prostate cancer xenograft tumor through targeting pro-apoptotic genes.

Background: Increasing evidence demonstrates that aberrantly regulated microRNAs (miRNAs) contribute to the initiation and progression of human cancer. We previously have demonstrated that miR-125b stimulated the growth of prostate cancer (CaP) cells. In this study, we further determined the influence of miR-125b on the pathogenesis of CaP.

Down-regulation of microRNA 106b is involved in p21-mediated cell cycle arrest in response to radiation in prostate cancer cells.

Background: microRNAs (miRNAs) are endogenous short non-coding RNAs, and play a pivotal role in regulating of a variety of cellular processes, including proliferation and apoptosis, both of which are cellular responses to radiation treatment. The purpose of this study is to identify candidate miRNAs whose levels are altered in response to radiation in prostate cancer cells and to investigate the molecular pathway of such miRNAs in the regulation of radiation-induced cellular response.

Methods: Using a miRNA microarray assay, we screened 132 cancerous miRNAs in LNCaP cells in response to radiation treatment.

Endogenous endophthalmitis after methicillin-resistant Staphylococcus aureus sternal wound infection.

Endogenous endophthalmitis is an extremely rare but sight-threatening complication of cardiac surgery. A high index of suspicion, prompt diagnosis and treatment, and early involvement of the ophthalmic surgeon is essential. We describe what we believe is the first case of endophthalmitis in a cardiac surgical patient with a methicillin-resistant Staphylococcus aureus wound infection.

Aortocoronary bypass graft fistula after surgical treatment of circumflex coronary artery fistula: a unique variation of a rare condition successfully treated with percutaneous embolization.

Multiple coronary artery fistulae are rare, complications can be life-threatening, and with large or symptomatic fistulae, intervention is mandatory. Both surgical and percutaneous interventions are well-described. We believe this is the first report of the embolization of an acquired fistula following initial surgical treatment of multiple congenital fistulae.

Plasmacytoid lymphoma within a left atrial myxoma: a rare coincidental dual pathology.

Primary malignant cardiac neoplasms are extremely rare. The occurrence of a malignant lymphoid tumour within a left atrial myxoma is highly atypical, with only one such case previously reported. Here, we describe a patient who presented with symptoms and signs of a left atrial myxoma.

MicroRNAs and prostate cancer.

Prostate cancer (CaP) is the most frequently diagnosed malignant tumour and the second leading cause of cancer deaths in American men. One of the most troubling aspects of this disease is that, after androgen ablation therapy, androgen-dependent cancer cells inevitably progress to an androgen-independent status, for which no effective treatment has yet been developed. To date, the mechanisms that underlie the occurrence and progression of CaP remain largely unknown.

Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen-dependent and independent prostate cancer cell lines.

Objective: To determine the benefit of genistein combined polysaccharide (GCP) in combination with the androgen receptor antagonist bicalutamide, the antimicrotubule taxane docetaxel, and the Src kinase inhibitor pp2 as part of a treatment regimen for advanced prostate cancer (CaP).

Materials And Methods: The growth inhibitory and apoptotic effects of GCP in combination with bicalutamide, docetaxel and pp2 were evaluated in both the androgen-dependent LNCaP line, and three androgen-independent lines: CWR22Rv1, PC-3, and LNCaP-R273H. The LNCaP-R273H model is an LNCaP variant expressing a p53(GOF) allele; like CWR22Rv1 and PC-3, it is able to grow in a minimal androgen environment.

An introductory educational module for cardiothoracic trainees.

In an attempt to enhance training we have developed an innovative introductory educational module for cardiothoracic trainees. Newly appointed cardiothoracic trainees at the Yorkshire Heart Centre in Leeds have piloted a 6-month programme, comprising 3 months attachment to the Cardiothoracic Intensive Care Unit, and 3 months seconded to allied departments. This report describes this programme, and considers its advantages and disadvantages.

Secondary transitional cell carcinoma and nitrogen mustard treatment.

Transitional cell carcinoma (TCC) of the bladder in children is a rare occurrence. Cyclophosphamide is a known risk factor for the development of TCC. Other alkylating agents, such as nitrogen mustard, have not been implicated in the development of secondary adult or pediatric TCC.