Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients.

Succinate dehydrogenase (SDH)-deficient renal carcinoma has been accepted as a provisional entity in the 2013 International Society of Urological Pathology Vancouver Classification. To further define its morphologic and clinical features, we studied a multi-institutional cohort of 36 SDH-deficient renal carcinomas from 27 patients, including 21 previously unreported cases. We estimate that 0.

ALK and ROS1 overexpression is very rare in colorectal adenocarcinoma.

Crizotinib, a small molecule tyrosine kinase inhibitor, has shown tremendous promise in the treatment of lung adenocarcinomas harboring either ALK or ROS1 rearrangements. Recently, small studies of colorectal carcinomas (CRCs) have suggested an incidence of EML4-ALK translocations of 0.4% to 2.

Personalising pancreas cancer treatment: When tissue is the issue.

The treatment of advanced pancreatic cancer has not moved much beyond single agent gemcitabine until recently when protocols such as FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) and nab-paclitaxel-gemcitabine have demonstrated some improved outcomes. Advances in technology especially in massively parallel genome sequencing has progressed our understanding of the biology of pancreatic cancer especially the candidate signalling pathways that are involved in tumourogenesis and disease course. This has allowed identification of potentially actionable mutations that may be targeted by new biological agents.

Loss of ARID1A expression in colorectal carcinoma is strongly associated with mismatch repair deficiency.

ARID1A is a tumor suppressor gene involved in chromatin remodelling. ARID1A mutations and loss of protein expression occur commonly in endometrioid and gynecological clear cell carcinoma where they are associated with mismatch repair (MMR) deficiency. We assessed ARID1A expression in a large cohort of colorectal carcinomas (CRCs).

Muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE) in the treatment of osteosarcoma.

Bacille Calmette-Guerin (BCG) has been used for decades as an immune stimulant to treat cancer. Early work by Fidler and Kleinerman identified muramyl dipeptide (MDP) as a critical component of the BCG cell wall which retained most of the immunostimulatory properties of the native BCG. Addition of a peptide to MDP resulted in muramyl tripeptide (MTP) which allowed incorporation into liposomal membranes.

Reflex ALK immunohistochemistry is feasible and highly specific for ALK gene rearrangements in lung cancer.

Fluorescence in situ hybridisation (FISH) is considered the gold standard for the detection of ALK gene rearrangements in lung adenocarcinoma. The presence of ALK gene rearrangement predicts response to specific targeted therapy, but these rearrangements are relatively rare and FISH studies are expensive, not widely available, potentially challenging to interpret and therefore difficult to undertake in all patients with non-small cell lung cancer. We developed and then deployed into the routine clinical setting a screening program for ALK gene rearrangement in all non-small cell lung cancer patients based on immunohistochemistry (IHC) with a mouse monoclonal antibody (clone 5A4).

Gemcitabine and CHK1 inhibition potentiate EGFR-directed radioimmunotherapy against pancreatic ductal adenocarcinoma.

Purpose: To develop effective combination therapy against pancreatic ductal adenocarcinoma (PDAC) with a combination of chemotherapy, CHK1 inhibition, and EGFR-targeted radioimmunotherapy.

Experimental Design: Maximum tolerated doses were determined for the combination of gemcitabine, the CHK1 inhibitor PF-477736, and Lutetium-177 ((177)Lu)-labeled anti-EGFR antibody. This triple combination therapy was investigated using PDAC models from well-established cell lines, recently established patient-derived cell lines, and fresh patient-derived xenografts.

Targeted CNS Delivery Using Human MiniPromoters and Demonstrated Compatibility with Adeno-Associated Viral Vectors.

Critical for human gene therapy is the availability of small promoter tools to drive gene expression in a highly specific and reproducible manner. We tackled this challenge by developing human DNA MiniPromoters using computational biology and phylogenetic conservation. MiniPromoters were tested in mouse as single-copy knock-ins at the locus on the X Chromosome, and evaluated for lacZ reporter expression in CNS and non-CNS tissue.

Lack of interleukin-17 leads to a modulated micro-environment and amelioration of mechanical hypersensitivity after peripheral nerve injury in mice.

Interleukin-17 (IL-17) is involved in a wide range of inflammatory disorders and in recruitment of inflammatory cells to injury sites. A recent study of IL-17 knock-out mice revealed that IL-17 contributes to neuroinflammation and neuropathic pain after peripheral nerve injury. Surprisingly, little is known of micro-environment modulation by IL-17 in injured sites and in pathologically related neuroinflammation and chronic neuropathic pain.

Models derived from in vitro analyses of spleen, liver, and lung leukocyte functions predict vaccine efficacy against the Francisella tularensis Live Vaccine Strain (LVS).

Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcriptional analyses, discriminated Francisella vaccines of different efficacies.

Identification of CHRNA5 rare variants in African-American heavy smokers.

Background: The common CHRNA5 mis-sense coding single-nucleotide polymorphism (SNP) rs16969968:G>A (D398N) has repeatedly been shown to confer risk for heavy smoking in individuals who carry the 'A' allele (encoding the 398N amino acid). The mis-sense SNP has a minor allele frequency of ∼40% in European-Americans, but only ∼7% in African-Americans (http://www.ncbi.

Basis for sex-specific expression of Takotsubo cardiomyopathy, cardiac syndrome X, and spontaneous coronary artery dissection.

Takotsubo cardiomyopathy, cardiac syndrome X, and spontaneous coronary artery dissection are cardiovascular syndromes with a predilection for women. A complex interplay between neurohormonal factors, genetic influences, anatomic alterations, and other factors together affect cardiovascular function. Specifically, a high, variable, or deficient estrogen state leads to vasomotor instability with propensity toward vasoconstriction and endothelial dysfunction that predispose women to myocardial impairment, microvascular dysfunction, and coronary arterial wall instability.

Adenoviral-mediated glial cell line-derived neurotrophic factor gene transfer has a protective effect on sciatic nerve following constriction-induced spinal cord injury.

Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown.

Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy.

Background: The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBM patients treated with BV at different recurrences.

Methods: We identified 468 primary GBM patients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV.

Succinate dehydrogenase deficiency is rare in pituitary adenomas.

Germline mutations in the succinate dehydrogenase genes (SDHA, SDHB, SDHC, and SDHD) are established as causes of pheochromocytoma/paraganglioma, renal carcinoma, and gastrointestinal stromal tumor. It has recently been suggested that pituitary adenomas may also be a component of this syndrome. We sought to determine the incidence of SDH mutation in pituitary adenomas.

Frozen section of the pancreatic neck margin in pancreatoduodenectomy for pancreatic adenocarcinoma is of limited utility.

The use of frozen section to assess resection margins intraoperatively during pancreaticoduodenectomy facilitates further resection. However, it is unclear whether this actually improves patient survival.We reviewed the overall survival and resection margin status in consecutive pancreaticoduodenectomies performed for carcinoma.

Trace vapour detection at room temperature using Raman spectroscopy.

A miniaturized flow-through system consisting of a gold coated silicon substrate based on enhanced Raman spectroscopy has been used to study the detection of vapour from model explosive compounds. The measurements show that the detectability of the vapour molecules at room temperature depends sensitively on the interaction between the molecule and the substrate. The results highlight the capability of a flow system combined with Raman spectroscopy for detecting low vapour pressure compounds with a limit of detection of 0.

Immunohistochemistry for myc predicts survival in colorectal cancer.

MYC over-expression as determined by molecular means has been reported as a favorable prognostic biomarker in colorectal carcinoma (CRC). However MYC expression analysis is not available in the routine clinical setting. We investigated whether immunohistochemistry (IHC) for the myc protein using a novel commercially available rabbit monoclonal antibody [clone Y69] which is currently in widespread clinical use for lymphoma diagnosis could be used to predict outcome in resected CRC.

Physician barriers to successful implementation of US Preventive Services Task Force routine HIV testing recommendations.

In 2006, the US Centers for Disease Control and Prevention issued recommendations supporting routine HIV testing in health care settings for all persons aged 13 to 64 years. Despite these recommendations, physicians are not offering HIV testing routinely. We apply a model that has previously identified 3 central, inter-related factors (knowledge-, attitude-, and behavior-related barriers) for why physicians do not follow practice guidelines in order to better understand why physicians are not offering HIV testing routinely.

Systematic review of the effects of exercise on activities of daily living in people with Alzheimer's disease.

OBJECTIVE. Alzheimer's disease (AD) results in a loss of independence in activities of daily living (ADLs), which in turn affects the quality of life of affected people and places a burden on caretakers. Limited research has examined the influence of physical training (aerobic, balance, and strength training) on ADL performance of people with AD.