Identify : the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer : a multicentre cohort study

Funding Action Bladder Cancer UK, The Rosetree Trust, The Urology Foundation. None had any involvement in the protocol stage of the study.Peer reviewedPublisher PD

IODP Expeditions 309 and 312 drill an intact section of upper oceanic basement into gabbros

The Integrated Ocean Drilling Program's (IODP) Expeditions 309 and 312 successfully completed the first sampling of an intact section of upper oceanic crust, through lavas and the sheeted dikes into the uppermost gabbros. Hole 1256D, which was initiated on the Ocean Drilling Program's (ODP) Leg 206, now penetrates to >1500 mbsf and >1250 m sub-basement. The first gabbroic rocks were encountered at 1407 mbsf. Below this, the hole penetrates 3c100 m into a complex zone of fractionated gabbros intruded into contact metamorphosed dikes

Towards personalized therapy for patients with malignant melanoma: molecular insights into the biology of BRAF mutations.

BRAF mutations have been identified as the most common oncogene mutation in melanomas, especially important in those originating on nonchronically sun-damaged skin. There is a large and continually growing body of evidence regarding the importance of this mutation in targeted therapy for melanoma. In this review, we outline these findings including: molecular pathways used by BRAF, the importance in nonmalignant neoplasms, histologic associations, the relationship of BRAF to KIT and NRAS mutations, and their impact on survival, as well as resistance mechanisms to BRAF inhibitors employed by melanoma. Understanding these topics and how they relate to one another may facilitate the development of new treatments and eventually improve the prognosis for those patients afflicted with this disease

Th2 activities induced during virgin T cell priming in the absence of IL-4, IL-13, and B cells.

Virgin T cells being primed to Th2-inducing or Th1-inducing Ags, respectively, start to synthesize IL-4 or IFN-gamma as they begin to proliferate. Parallel respective induction of B cells to produce gamma1 or gamma2a switch transcripts provides additional evidence of early divergent Th activity. This report concerns the roles of IL-4, IL-13, and B cells in these early events in vivo. Th2 responses were induced in lymph nodes against hapten-protein given s.c. with killed Bordetella pertussis adjuvant. In T cell proliferation in wild-type mice, IL-4 message up-regulation and gamma1 and epsilon switch transcript production were underway 48-72 h after immunization. The absence of IL-4, IL-13, or B cells did not alter the early T cell proliferative response. The gamma1 and epsilon switch transcript production was still induced in the absence of IL-4, IL-13, or both, but at a reduced level, while the dominance of switching to IgG1 in the extrafollicular hapten-specific plasma cell response was retained. The up-regulation of IL-4 message was not reduced or delayed in the absence of B cells and was only marginally reduced by the absence of IL-13. It is concluded that signals delivered by dendritic cells, which are not dependent on the presence of IL-4, IL-13, or B cells, can prime virgin T cells and induce the early Th2 activities studied. These early events that direct virgin T cells toward Th2 differentiation contrast with the critical later role of Th2 cytokines in selectively expanding Th2 clones and driving further IL-4 synthesis

KRAS mutation is present in a small subset of primary urinary bladder adenocarcinomas.

Histopathology KRAS mutation is present in a small subset of primary urinary bladder adenocarcinomas Aims:  To determine whether KRAS mutations occur in primary bladder adenocarcinoma. Methods and results:  Twenty-six cases of primary urinary bladder adenocarcinoma were analysed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and amplified with shifted termination assay technology, which recognizes wild-type or mutant target sequences and selectively extends detection primers with labelled nucleotides. A mutation in KRAS was found in three (11.5%) of 26 primary bladder adenocarcinomas. Two of these three cases exhibited a G13D mutation, whereas the remaining case contained a mutation in G12V. None of the ten cases of urothelial carcinoma with glandular differentiation displayed KRAS mutation. Colonic adenocarcinoma contained a KRAS mutation in 18 (33%) of 55 cases. There was no distinct difference with regard to grade, stage or outcome according to the limited clinicopathological data available. However, the two youngest patients, aged 32 and 39 years, in our study group, with a mean population age of 61 years, were found to have mutations in KRAS. Conclusions:  KRAS mutations are present in a small subset of primary urinary bladder adenocarcinomas. Future clinical trials for treatment of bladder adenocarcinoma, employing targeted therapies similar to those used for treatment of colon cancer, may also benefit from the predictive implications of KRAS mutational testing

EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder.

The identification of mutations in epidermal growth factor receptor (EGFR) and translocations involving anaplastic lymphoma kinase (ALK) in lung adenocarcinoma has drastically changed understanding of the disease and led to the development of targeted therapies. Adenocarcinoma of the urinary bladder is rare and poorly understood at the molecular level. We undertook this study to determine whether EGFR mutations, increases in EGFR copy number, or ALK translocations are present in these tumors. Twenty-eight cases of primary bladder adenocarcinoma were analyzed. For EGFR mutational analysis, PCR-amplified products were analyzed on the Q24 Pyrosequencer with Qiagen EGFR Pyro Kits. All cases were analyzed via fluorescence in situ hybridization (FISH) using Vysis ALK Break Apart FISH Probes for detection of ALK chromosomal translocation and Vysis Dual Color Probes to assess for increased gene copy number of EGFR. None of the 28 cases examined showed mutational events in EGFR or ALK rearrangements. EGFR polysomy was seen in 10 out of 28 (36%) cases. No correlation with EGFR polysomy was seen in the tumors with respect to age, histologic subtypes, pathologic stage, or lymph node metastasis. In summary, EGFR mutations and ALK rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. A subgroup of cases (36%), however, demonstrated increased gene copy number of EGFR by FISH