Bronchioalveolar organoids: A preclinical tool to screen toxicity associated with antibody-drug conjugates.

Despite extensive preclinical testing, cancer therapeutics can result in unanticipated toxicity to non-tumor tissue in patients. These toxicities may pass undetected in preclinical experiments due to modeling limitations involving poor biomimicry of 2-dimensional in vitro cell cultures and due to lack of interspecies translatability in in vivo studies. Instead, primary cells can be grown into miniature 3-dimensional structures that recapitulate morphological and functional aspects of native tissue, termed "organoids.

Elimination of tucatinib, a small molecule kinase inhibitor of HER2, is primarily governed by CYP2C8 enantioselective oxidation of gem-dimethyl.

Purpose: Tucatinib, a small molecule for the treatment of metastatic HER2-positive breast cancer, was extensively metabolized in humans to multiple oxidative metabolites. To fully understand the elimination and biotransformation pathways of tucatinib, we investigated the in vitro and in vivo metabolism of tucatinib, and also conducted a Phase I trial using [C]tucatinib.

Methods: To identify the responsible enzymes for tucatinib clearance, we investigated the in vitro metabolism of tucatinib including enzyme phenotyping, which facilitated the discovery of several metabolites in human and monkey plasma and excreta, in particular M1 (ONT-993, an aliphatic hydroxylated metabolite).

Persistence of Trichomonas vaginalis serostatus in men over time.

Purpose: Previous epidemiologic studies have observed positive associations between Trichomonas vaginalis (Tv) serostatus and both prostate cancer (PCa) risk and mortality. However, only a few small older studies have examined Tv antibody persistence over time, all of which were composed mainly of female patients. Therefore, we examined Tv antibody persistence over time, as well as intra-individual variability, among middle- to older-aged men in the Southern Community Cohort Study (SCCS).

Epitopes of the highly immunogenic Trichomonas vaginalis α-actinin are serodiagnostic targets for both women and men.

There is a need for a point-of-care serodiagnostic test for women and men for sexually transmitted infections (STIs) caused by Trichomonas vaginalis. Sera from women with this STI and sera from men that were analyzed in studies showing a relationship between serostatus and prostate cancer are highly seropositive in response to trichomonad α-actinin and its truncated protein (ACT-P2) (positive control sera). Epitope mapping experiments showed that positive control sera from women had antibodies to 13 distinct epitopes, 5 of which were detected by positive control sera from men.

Identification, characterization, and synthesis of peptide epitopes and a recombinant six-epitope protein for Trichomonas vaginalis serodiagnosis.

There is a need for a rapid, accurate serodiagnostic test useful for both women and men infected by Trichomonas vaginalis, which causes the number one sexually transmitted infection (STI). Women and men exposed to T. vaginalis make serum antibody to fructose-1,6-bisphosphate aldolase (ALD), α-enolase (ENO), and glyceraldehyde-3-phosphate dehydrogenase (GAP).

Crystallization and initial crystallographic analysis of phosphoglucosamine mutase from Bacillus anthracis.

The enzyme phosphoglucosamine mutase catalyzes the conversion of glucosamine 6-phosphate to glucosamine 1-phosphate, an early step in the formation of the nucleotide sugar UDP-N-acetylglucosamine, which is involved in peptidoglycan biosynthesis. These enzymes are part of the large alpha-D-phosphohexomutase enzyme superfamily, but no proteins from the phosphoglucosamine mutase subgroup have been structurally characterized to date. Here, the crystallization of phosphoglucosamine mutase from Bacillus anthracis in space group P3(2)21 by hanging-drop vapor diffusion is reported.

Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells.

SU5416 is a selective inhibitor of vascular endothelial growth factor (VEGF) receptors with anti-angiogenesis activity for human cancers. We have previously reported that SU5416 sensitizes ovarian cancer cells to cisplatin via suppression of nucleotide excision repair activity. This study sought to gain further insights into the mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells.

Is sudden infant death syndrome associated with Helicobacter pylori infection in children?

Helicobacter pylori infection has recently been implicated in the pathogenesis of sudden infant death syndrome (SIDS). We investigated this association. Twenty-five pairs of gastric and tracheal tissue specimens obtained from autopsies of 25 children with previous diagnoses of SIDS were available for this study.

Reuse of negative CLOtest kits in children.

Background: The rapid urease test, CLOtest, is used frequently in endoscopy suites. In the developed world, a negative CLOtest result is extremely common. The question of whether reuse of previously negative CLOtest kits is appropriate in children and the cost saving of such a practice were investigated.

Helicobacter pylori serology and the diagnosis of H. pylori infection in children.

Serological screening accuracy rate may be dependent on clinical and pathological determinants. The aim of this study was to evaluate the accuracy of Hp serology test (Roche Biomedical Lab., Labcorp), in the diagnosis of Hp infection in 121 children who were seen in the Pediatric Gastoenterology Clinic at the Marshall University Joan C.

Tryosine kinase and ornithine decarboxylase activation in children with Helicobactor pylori gastritis.

H. pylori infection has been considered a risk factor for the development of gastric malignancy. Ornithine decarboxylase and tyrosine kinases activities are increased in patients with colon or esophageal cancer.

Helicobacter pylori antibody profile in household members of children with H. pylori infection.

Intrafamilial spread is implicated as a major route for acquisition of Helicoobacter pylori infection. Investigating H. pylori cytotoxin-associated protein (CagA) and vacuolating toxin (VacA) antibodies within family members enabled the authors to evaluate this possibility further.

Detection of Helicobacter pylori organisms by Hp-fast in children.

Hp-fast is a new rapid urease test (RUT) that has not been evaluated in children. The aim of the study was to prospectively compare the Hp-fast test to the CLOtest in children. Children with gastrointestinal symptoms who undergo diagnostic upper endoscopy were prospectively enrolled to the study.

Prevalence of CagA, VacA antibodies in symptomatic and asymptomatic children with Helicobacter pylori infection.

Background: Limited data are available on the prevalence of CagA and VacA Helicobacter pylori antibodies in children. The aim of this study was to investigate the antibody prevalence to the H. pylori virulence factors CagA and VacA in symptomatic and asymptomatic children with H.

Human vaginal mucosal immune system: characterization and function.

Objective: The mucosal immune system has been recognized as the first line of defense against foreign antigens. The limited information available on the mucosal immunity of the lower reproductive organs have restricted our ability to fight infections, especially, the sexually transmitted disease. The aim of this study was to characterize in-vitro the human vaginal lamina propria lymphocytes (VLPL), their cell surface phenotypes, and cellular function.

Prevalence of Helicobacter pylori infection in children from urban and rural West Virginia.

Our objective was to evaluate the prevalence rate of Helicobacter pylori (HP) in children from urban and rural areas of West Virginia. In all, 1164 blood samples were collected from children who attended a local health fair, pediatric clinics, and emergency departments of four different hospitals located in urban and rural counties. Socioeconomic status was determined in 303 children.

Immunosuppressive effect of budesonide on human lamina propria lymphocytes.

Budesonide, a beta-adreno-receptor agonist, is comparable to corticosteroid in the treatment of patients with inflammatory bowel disease with the advantage of minimal side effect. Although the immunomodulatory effects of budesonide on the circulatory and respiratory mucosal immune system have been reported, its effect on the human gut immune system has not been published. In this study, the effect of budesonide on the human gut immune system was compared to methyl-prednisolone.

Comparison between a rapid office-based and ELISA serologic test in screening for Helicobacter pylori in children.

Background: The rapid diagnostic serological test for detection of Helicobacter pylori (H. pylori) infection in children has a significant advantage over the standard enzyme immunoassay (EIA) method, for its simplicity and rapid availability of results in a physician's office setting. We compared the immunochromatographic test with a standard enzyme immunoassay test in the pediatric population.

Vitamin A and retinoic acids immunomodulation on human gut lymphocytes.

Epidemiological studies have suggested an important immunomodulatory role for vitamin A and other related vitamin A compounds in adults and children. Although vitamin A is absorbed via the gastrointestinal tract, its affect on the gut mucosal immune cells has not been adequately investigated. We investigated the in-vitro effect of vitamin A (retinol) and its retinoid acid (RA) compounds (13-cis- and all trans-retinoic acids) on the human gut mucosal immune system as represented by colonic lamina propria lymphocyte (LPL) proliferation, and ornithine decarboxylase (ODC) activity.