We report the design, synthesis, electrochemical, UV-vis, fluorescence, and computational study of nine π-linked donor-acceptor (D-π-A) chromophores. The series of novel compounds comprises a terphenyl, terthiophene, or 2,5-diphenyl thiophene linker, with one electron-donating group (methyl or ,-diethyl) and one electron-withdrawing group (nitrone, formyl, or dicyanovinyl) at opposite ends of the molecule. The HOMO-LUMO gaps were determined cyclic voltammetry and found to correspond well to DFT-calculated values.
View Article and Find Full Text PDFWe assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity.
View Article and Find Full Text PDFBackground: The phase III S0819 trial investigated addition of cetuximab to first-line chemotherapy (CT) in NSCLC. Subgroup analyses suggested an OS benefit among patients with EGFR copy number gain in squamous cell carcinomas (SCC), (HR = 0.58 [0.
View Article and Find Full Text PDFCancer Chemother Pharmacol
August 2021
Purpose: Aurora kinases are overexpressed or amplified in numerous malignancies. This study was designed to determine the safety and tolerability of the Aurora A kinase inhibitor alisertib (MLN8237) when combined with weekly irinotecan.
Methods: In this single-center phase 1 study, adult patients with refractory advanced solid tumors received 100 mg/m irinotecan intravenously on day 1 and 8 of a 21-day cycle.
Gastrointest Endosc Clin N Am
April 2021
Video capsule endoscopy and device-assisted enteroscopy are complementary technologies. Capsule endoscopy is a highly acceptable technology with high diagnostic yield that can guide a subsequent enteroscopy approach. This article aims to focus on the role of video capsule endoscopy as a prelude to deep enteroscopy with a focus on the strengths and limitations of either approach.
View Article and Find Full Text PDFWe sought to enumerate secondary medical conditions from hospitalization records in adolescent and young adult (AYA) differentiated thyroid cancer (DTC) survivors and identify characteristics of patients with increased likelihood of subsequent medical diagnoses. Using data from the California Cancer Registry and statewide hospitalization data, we examined incident oncologic, endocrine, pulmonary, hematologic, and cardiovascular diagnoses in 12,312 AYA (aged 15-39) patients diagnosed with DTC in 1996-2012 and surviving >2 years after diagnosis with follow-up through 2014. We calculated the cumulative incidence of each condition accounting for the competing risk of death and used multivariable Cox proportional hazards regression to evaluate sociodemographic and clinical characteristics associated with each incident condition.
View Article and Find Full Text PDFFOLFOX is one of the most effective treatments for advanced colorectal cancer. However, cumulative oxaliplatin neurotoxicity often results in halting the therapy. Oxaliplatin functions predominantly via the formation of toxic covalent drug-DNA adducts.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease with no cure and limited treatment options. Patients experience a gradual paralysis leading to death from respiratory complications on average only 2-5 years after diagnosis. There is increasing evidence that skeletal muscle is affected early in the disease process, yet the pathological processes occurring in the skeletal muscle of ALS patients are still mostly unknown.
View Article and Find Full Text PDFCancer Chemother Pharmacol
October 2018
Purpose: Tyrosine kinase inhibitors (TKI) that target MET signaling have shown promise in various types of cancer, including lung cancer. Combination strategies have been proposed and developed to increase their therapeutic index. Based on preclinical synergy between inhibition of MET and topoisomerase I, a phase I study was designed to explore the combination of topotecan with the MET TKI tivantinib.
View Article and Find Full Text PDFBackground: In an era of rising differentiated thyroid cancer incidence, the rate and impact of neck reoperation may inform the intensity of earlier interventions and surveillance. This study sought to define predictors of neck reoperation and to assess its impact on survival.
Methods: Using the California Cancer Registry linked to the California Office of Statewide Health Planning and Development records, a retrospective cohort study was performed of 24,230 patients with total or near-total thyroidectomy for papillary or follicular thyroid cancer between 1991 and 2008 and follow-up through 2013.
Purpose: The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC).
View Article and Find Full Text PDFBackground: EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.
Methods: We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico.
Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pT) conversion and promoting T1 immunity to dietary antigen.
View Article and Find Full Text PDFBackground: Overall response rate is frequently used as an end point in phase 2 trials of platinum-treated extensive stage (ES) small-cell lung cancer (SCLC). We hypothesized that disease control rate (DCR) would be a superior surrogate for subsequent survival outcomes.
Methods: Updated patient-level data from Southwest Oncology Group (SWOG) trials in second- and/or third-line ES-SCLC patients were pooled.
Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor-independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues.
View Article and Find Full Text PDFBackground & Aims: The mechanisms of tissue destruction during progression of celiac disease are poorly defined. It is not clear how tissue stress and adaptive immunity contribute to the activation of intraepithelial cytotoxic T cells and the development of villous atrophy. We analyzed epithelial cells and intraepithelial cytotoxic T cells in family members of patients with celiac disease, who were without any signs of adaptive antigluten immunity, and in potential celiac disease patients, who have antibodies against tissue transglutaminase 2 in the absence of villous atrophy.
View Article and Find Full Text PDFBackground: In contrast to colon cancer, the implications of reduced lymph node retrieval in rectal cancer are unclear.
Methods: Using the California Cancer Registry, we performed a retrospective cohort study of 4790 patients with stage I - III rectal cancer diagnosed from 2000 to 2007 who underwent tri-modality therapy. Using multivariate Cox proportional hazards models adjusted for age, sex, race, socioeconomic status, T-stage, and lymph node numbers, we evaluated rectal cancer specific survival (RC-SS) in neoadjuvant and adjuvant cohorts in the overall population and amongst those without involved lymph nodes (pN0).
Background: Differentiated thyroid cancer (DTC) is among the most common malignancies in the adolescent and young adult (age 15-39 years) population, and its incidence is rising. Younger age (<45 years) is an important prognostic indicator and is incorporated into the TNM classification system. This study hypothesized that this would result in distinct treatment patterns for younger and older patients.
View Article and Find Full Text PDFPurpose: This phase I study examined the toxicity and tolerability of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies.
Experimental Design: Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, Zubrod performance status 0-2, and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.
Background: Extensive-stage small-cell lung cancer (SCLC) patients who progress after platinum-based chemotherapy are traditionally categorized as platinum sensitive (progression ≥ 90 days from last platinum dose) or refractory (progression < 90 days), a practice arising from seminal observations of worse survival in refractory patients. Subsequent trials accounted for platinum sensitivity, resulting in higher sample sizes and increased resource use.
Methods: To assess whether platinum-sensitivity status remains associated with outcomes, patient-level data from recent Southwest Oncology Group trials in second- and/or third-line extensive-stage SCLC were pooled.
Purpose: Erlotinib marginally improves survival when administered continuously with gemcitabine to patients with advanced pancreatic cancer; however, preclinical data suggest that there is antagonism between chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors when these are delivered concurrently. We tested a pharmacodynamic separation approach for erlotinib plus gemcitabine and interrogated EGFR signaling intermediates as potential surrogates for the efficacy of this strategy.
Methods: Patients with measurable, previously untreated locally advanced unresectable or metastatic pancreatic cancer were treated with gemcitabine 1000 mg/m(2) as an intravenous infusion over 30-min on days 1, 8, 15 and erlotinib 150 mg/day on days 2-5, 9-12, 16-26 of each 28-day cycle.
Inhibition of either vascular endothelial growth factor receptor or mammalian target of rapamycin (mTOR) signaling improves outcomes in patients with several advanced solid tumors. We conducted a phase I trial of temsirolimus with pazopanib to investigate the feasibility of simultaneous 'vertical inhibition' of vascular endothelial growth factor receptor and mTOR pathways. Patients with advanced solid tumors, no previous pazopanib or mTOR inhibitor, good performance status, and acceptable end-organ function were eligible.
View Article and Find Full Text PDFCeliac disease is a common inflammatory disease of the small intestine triggered by gluten in genetically susceptible individuals. Diagnosis is made by serologic testing and upper endoscopy with small bowel biopsy in most individuals. Celiac patients may present with abdominal pain or nonspecific gastrointestinal complaints that result in radiologic imaging before diagnosis of celiac disease.
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