Assessing safety and efficacy of a novel glucose-free amino acid oral rehydration solution for watery diarrhea management in children: a randomized, controlled, phase III trial.

Background: Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy (ORT), its adoption remains low. Glucose-based ORS (GORS) is the standard, but novel formulations like glucose-free amino acid-based VS002A have emerged as potential alternatives.

Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials.

Purpose: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain.

Materials And Methods: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors.

Results: MSI status was available for 5,457 patients (609 MSI, 11.

An Amino Acid-Based Oral Rehydration Solution Regulates Radiation-Induced Intestinal Barrier Disruption in Mice.

Background: Radiotherapy inadvertently affects gastrointestinal (GI) epithelial cells, causing intestinal barrier disruption and increased permeability.

Objective: We examined the effect of amino acid-based oral rehydration solution (AA-ORS) on radiation-induced changes of intestinal barrier function and epithelial tight junctions (TJs) in a randomized experimental study using a total-body irradiation (TBI) mouse model.

Methods: Eight-week-old male Swiss mice received a single-dose TBI (0, 1, 3, or 5 Gy), and subsequent gastric gavage with AA-ORS (threonine, valine, serine, tyrosine, and aspartic acid) or saline for 2 or 6 d.

The adaptive regulation of thiamine pyrophosphokinase-1 facilitates malignant growth during supplemental thiamine conditions.

Supplemental levels of vitamin B1 (thiamine) have been implicated in tumor progression. Tumor cells adaptively up-regulate thiamine transport during hypoxic stress. Upon uptake, thiamine pyrophosphokinase-1 (TPK1) facilitates the rapid phosphorylation of thiamine into thiamine pyrophosphate (TPP).

Targeting CD26 suppresses proliferation of malignant mesothelioma cell via downmodulation of ubiquitin-specific protease 22.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is associated with a poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on cell cycle control of MPM cells by targeting CD26 molecule with humanized anti-CD26 monoclonal antibody (HuCD26mAb), focusing particularly on ubiquitin-specific protease 22 (USP22).

Ussing Chamber Technique to Measure Intestinal Epithelial Permeability.

Epithelial cells are polarized and have tight junctions that contribute to barrier function. Assessment of barrier function typically involves measurement of electrophysiological parameters or movement of nonionic particles across an epithelium. Here, we describe measurement of transepithelial electrical conductance or resistance, determination of dilution potential, and assessment of flux of nonionic particles such as dextran or mannitol, with particular emphasis on Ussing chamber techniques.

Performance of the HPV-16 L1 methylation assay and HPV E6/E7 mRNA test for the detection of squamous intraepithelial lesions in cervical cytological samples.

HPV-16 L1 methylation and E6/E7 mRNA have suggested that they had close relationship with cervical neoplastic progression. This study aimed to evaluate the clinical performance of the HPV-16 L1 methylation assay and E6/E7 mRNA test for detecting high-grade cervical lesions (CIN2+). A total of 81 women with liquid-based cytology (LBC) samples, histological results, and positive HPV-DNA test for HPV type 16 only were included in this study.

Displacement of the Spleen Mimicking Renal Cell Cancer Recurrence Post-Nephrectomy: A Case Report.

Local regional recurrence of renal cell cancer post-nephrectomy most often occurs within three years after surgery. Post-nephrectomy, many processes may mimic RCC recurrence. We present the case of a 75 year-old Caucasian male patient with a mass in his renal fossa post-nephrectomy for renal cell cancer, suggesting local recurrence.

Florida Initiative for Quality Cancer Care: Changes in Psychosocial Quality of Care Indicators Over a 3-Year Interval.

Purpose: Identifying and addressing psychosocial concerns is increasingly recognized as an important aspect of cancer care that needs to be improved. As part of the Florida Initiative for Quality Cancer Care, medical record reviews were conducted to evaluate cancer care, including psychosocial care, at oncology practices in Florida in 2006. Results were subsequently disseminated to the practices, and performance was reassessed at the same practices in 2009.

Race and ethnicity influences collection of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells from unrelated donors, a Center for International Blood and Marrow Transplant Research analysis.

Little information exists on the effect of race and ethnicity on collection of peripheral blood stem cells (PBSC) for allogeneic transplantation. We studied 10,776 donors from the National Marrow Donor Program who underwent PBSC collection from 2006 to 2012. Self-reported donor race/ethnic information included Caucasian, Hispanic, Black/African American (AA), Asian/Pacific Islander (API), and Native American (NA).

Florida Initiative for Quality Cancer Care: improvements in breast cancer quality indicators during a 3-year interval.

Background: The Florida Initiative for Quality Cancer Care (FIQCC), composed of 11 practice sites across Florida, conducted its initial evaluation of adherence to breast cancer quality of care indicators (QCI) in 2006, with feedback provided to encourage quality improvement efforts at participating sites. In this study, our objective was to reassess changes over time resulting from these efforts.

Study Design: Quality care indicators were derived from the Quality Oncology Practice Initiative, the National Comprehensive Cancer Network, the American College of Surgeons, and expert panel consensus.

An amino acid mixture mitigates radiation-induced gastrointestinal toxicity.

Electrolyte and nutrient absorption occur in villous epithelial cells. Radiation often results in reduced electrolyte and nutrient absorption, which leads to gastrointestinal toxicity. Therefore, the authors studied: (1) radiation-induced changes in glucose and amino acid absorption across ileal tissues and (2) the effect of amino acid mixtures on absorptive capacity.

Mitochondrial DNA and functional investigations into the radiosensitivity of four mouse strains.

We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA ratios are significant to mitochondrial function and if a material effect on mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6 (radioresistant), and F1 hybrid mouse strains were exposed to total body irradiation. Hepatic genomic DNA was extracted, and mitochondria were isolated.

Modulation of blood flow, hypoxia, and vascular function in orthotopic prostate tumors during exercise.

Background: Previous studies have hypothesized that tumor blood flow may be elevated or reduced during exercise, which could impact the tumor microenvironment. However, to date technical limitations have precluded the measurement of tumor blood flow during exercise. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that during exercise tumors would experience 1) diminished vascular resistance, 2) augmented blood flow, 3) increased numbers of perfused vessels, and 4) decreased tissue hypoxia and, furthermore, that the increased perfusion would be associated with diminished vasoconstriction in prostate tumor arterioles.

Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.

Abnormal vascularization of solid tumours results in the development of microenvironments deprived of oxygen and nutrients that harbour slowly growing and metabolically stressed cells. Such cells display enhanced resistance to standard chemotherapeutic agents and repopulate tumours after therapy. Here we identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues.

Glucose stimulates calcium-activated chloride secretion in small intestinal cells.

The sodium-coupled glucose transporter-1 (SGLT1)-based oral rehydration solution (ORS) used in the management of acute diarrhea does not substantially reduce stool output, despite the fact that glucose stimulates the absorption of sodium and water. To explain this phenomenon, we investigated the possibility that glucose might also stimulate anion secretion. Transepithelial electrical measurements and isotope flux measurements in Ussing chambers were used to study the effect of glucose on active chloride and fluid secretion in mouse small intestinal cells and human Caco-2 cells.

CD9 negatively regulates CD26 expression and inhibits CD26-mediated enhancement of invasive potential of malignant mesothelioma cells.

CD26/dipeptidyl peptidase IV is a cell surface glycoprotein which consists of multiple functional domains beside its ectopeptidase site. A growing body of evidence indicates that elevated expression of CD26 correlates with disease aggressiveness and invasive potential of selected malignancies. To further explore the molecular mechanisms involved in this clinical behavior, our current work focused on the interaction between CD26 and CD9, which were recently identified as novel markers for cancer stem cells in malignant mesothelioma.

Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031.

We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m(2)/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1-21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes.

Florida Initiative for Quality Cancer Care: improvements on colorectal cancer quality of care indicators during a 3-year interval.

Background: The quality of cancer care has become a national priority; however, there are few ongoing efforts to assist medical oncology practices in identifying areas for improvement. The Florida Initiative for Quality Cancer Care is a consortium of 11 medical oncology practices that evaluates the quality of cancer care across Florida. Within this practice-based system of self-assessment, we determined adherence to colorectal cancer quality of care indicators (QCIs) in 2006, disseminated results to each practice and reassessed adherence in 2009.

CD26 expression on T-anaplastic large cell lymphoma (ALCL) line Karpas 299 is associated with increased expression of versican and MT1-MMP and enhanced adhesion.

Background: CD26/dipeptidyl peptidase IV (DPPIV) is a multifunctional membrane protein with a key role in T-cell biology and also serves as a marker of aggressive cancers, including T-cell malignancies.

Methods: Versican expression was measured by real-time RT-PCR and Western blots. Gene silencing of versican in parental Karpas 299 cells was performed using transduction-ready viral particles.

Lessons learned from radiation oncology clinical trials.

A workshop entitled "Lessons Learned from Radiation Oncology Trials" was held on December 7-8, 2011, in Bethesda, MD, to present and discuss some of the recently conducted radiation oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the preclinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions: (i) opportunities to learn from null-hypothesis trials through tissue and imaging studies; (ii) value of preclinical data supporting the design of combinatorial therapies; (iii) significance of validated biomarkers; (iv) necessity of quality assurance in radiotherapy delivery; (v) conduct of sufficiently powered studies to address the central hypotheses; and (vi) importance of publishing results of the trials regardless of the outcome.

PKR negatively regulates leukemia progression in association with PP2A activation, Bcl-2 inhibition and increased apoptosis.

Reduced expression and activity of the proapoptotic, double-stranded RNA-dependent protein kinase, PKR (protein kinase R) is observed in breast, lung and various leukemias, suggesting that loss of PKR potentiates transformation. Now we report that decreased PKR activity inhibits chemotherapy-induced apoptosis of leukemia cells both in vitro and in vivo. Inhibition of PKR expression or activity reduces protein phosphatase 2A (PP2A) activity, a B-cell lymphoma 2 (Bcl-2) phosphatase, resulting in enhanced Bcl-2 phosphorylation.