T-cell expression of AhR inhibits the maintenance of pT cells in the gastrointestinal tract in acute GVHD.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4 T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT.

Randomized phase II study of IL-2 with or without an allogeneic large multivalent immunogen vaccine for the treatment of stage IV melanoma.

Objective: To evaluate the activity of interleukin-2 (IL-2) in combination with allogeneic large multivalent immunogen (LMI) vaccine, prepared by immobilizing SK23-CD80 melanoma cell line plasma membrane on 5-μm-diameter silica beads, in patients with melanoma.

Methods: Twenty-one patients with metastatic melanoma were randomly assigned to an IL-2 alone control group or an IL-2 plus LMI vaccine treatment group. The primary objective was to evaluate the progression-free survival (PFS) of each group.

Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer.

Introduction: Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.

Methods: The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC.

Fibroblast growth factor receptor signaling through MEK-ERK is required for prostate bud induction.

The urogenital sinus (UGS) is specified as prostate in mice around embryonic day 15.5 as indicated by expression of the transcription factor Nkx3.1.

Suppression of mammary gland carcinogenesis by post-initiation treatment of rats with tamoxifen or indole-3-carbinol or their combination.

This study examined whether suppression of mammary gland carcinogenesis elicited by low doses of tamoxifen (TAM) can be enhanced by concomitant treatment of rats with indole-3-carbinol (I3C), a component of cruciferous vegetables and a dietary supplement used for its putative antiestrogenicity. Two weeks after one oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) at 65 mg/kg body weight, female Sprague-Dawley rats started treatment with TAM (10 microg/rat) by subcutaneous injection, I3C (250 mg/kg body weight) by oral gavage, TAM+I3C or their respective vehicles three times per week, for up to 20 weeks. Significant increases in the median latency of malignant mammary tumors and decreases in the mean tumor mass per rat were due to TAM.

The mouse seminal vesicle shape mutation is allelic with Fgfr2.

The mouse seminal vesicle shape (svs) mutation is a spontaneous recessive mutation that causes branching morphogenesis defects in the prostate gland and seminal vesicles. Unlike many other mutations that reduce prostatic and/or seminal vesicle branching, the svs mutation dramatically reduces branching without reducing organ growth. Using a positional cloning approach, we identified the svs mutant lesion as a 491 bp insertion in the tenth intron of Fgfr2 that results in changes in the pattern of Fgfr2 alternative splicing.

Bladder cancer: toward state of the art multidisciplinary molecular medicine.

Recent advances in bladder cancer research, and clinical diagnosis and therapy are explored. Major advances in biologic understanding are applied toward better early diagnosis and staging. Using molecular medicine to help informed clinical trial design and implementation will lead to more effective therapeutic intervention in transitional cell carcinoma.

Repressible transgenic model of NRAS oncogene-driven mast cell disease in the mouse.

To create a model in which to study the effects of RAS dysregulation in hematopoietic disease, we developed separate founder lines of transgenic mice, with the tetracycline transactivator (tTA) driven by the Vav hematopoietic promoter in one line and NRASV12 driven by the tetracycline responsive element (TRE2) in the other. When these lines are crossed, doubly transgenic animals uniformly develop a disease similar to human aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL) when they are between 2 and 4 months of age. Disease is characterized by tissue infiltrates of large, well-differentiated mast cells in the spleen, liver, skin, lung, and thymus.

Colorectal cancer in inflammatory bowel disease: a continuing problem.

Purpose: Because of the increased risk of colorectal cancer in patients with inflammatory bowel disease, surveillance colonoscopy with mucosal biopsies for dysplasia has been advocated to prevent malignancy or permit its early diagnosis. However, despite adoption of colonoscopic surveillance programs by many clinicians, we have noted a pattern of continued referrals for inflammatory bowel disease-associated malignancy. This study was undertaken in an effort to characterize this cohort of patients.