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Biomedical subjects

T D Nguyen

Publications and source records attributed to T D Nguyen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

PURPOSE: To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS: A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS: Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION: This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

Adenocarcinoma↗
PubMed1998

Studies of the cellular distribution of superoxide dismutases in adult and fetal rat tissues.

Activities of three types of superoxide dismutase in tissue fractions were significantly lower in fetal and adult brain and fetal limb preparations than in fetal and adult heart preparations. An exception was the cytoplasmic fraction of adult brain that had levels of Cu, Zn-superoxide dismutase activity comparable to those in cytoplasmic fractions of heart. In addition, Mn superoxide dismutase activity appeared to be very low in all fetal mitochondrial matrix fractions and cytoplasmic fractions as well as in adult brain. Finally, the results of these studies emphasize the importance of two antioxidant defense systems in the tissues studied, one associated with the mitochondrial electron transport system and the other, the cytosolic Cu, Zn enzyme.

Animals↗
PubMed1998

Localization of the stress proteins alpha B-crystallin and trabecular meshwork inducible glucocorticoid response protein in normal and glaucomatous trabecular meshwork.

PURPOSE: To examine the differential staining of two potential stress-response markers, alpha B-crystallin and the trabecular meshwork inducible glucocorticoid response protein (TIGR), in meshwork from normal and glaucomatous human eyes. METHODS: Trabecular meshwork from 35 eyes from 23 donors with either primary open-angle glaucoma, pseudoexfoliative glaucoma, or low-tension glaucoma, and from age-matched normal eyes, was examined. Sagittal and tangential frozen sections were stained with polyclonal antibodies to alpha B-crystallin or TIGR and then by a fluorescent secondary antibody. RESULTS: In normal eyes, labeling for alpha B-crystallin occurred in the subendothelial region of Schlemm's canal and outer corneoscleral regions, whereas TIGR labeling was found in the inner uveal meshwork region and the anterior portion of the meshwork. In contrast, in many glaucomatous eyes, labeling for alpha B-crystallin and TIGR occurred in more regions of the meshwork and appeared more intense than in normal eyes, regardless of the type or clinical severity of glaucoma. CONCLUSIONS: The differences in localization of alpha B-crystallin and TIGR may relate to functional specialization within meshwork tissues. The increase in the staining for these proteins in glaucomatous eyes could involve environmental and genetic factors in the disease processes.

Aged↗
PubMed1997

Identification of a gene that causes primary open angle glaucoma.

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.

Base Sequence↗
PubMed1997

Contrasting effects of T cell growth factors on T cell responses to melanoma in vitro.

Determinants of T cell responses to tumor cells remain largely unknown. In the present study we have used long-term cultures of human melanoma cells and autologous peripheral blood lymphocytes to examine the influence of cytokines with T cell growth activity on the phenotype and cytotoxic and proliferative response of T cells to melanoma. It was found that addition of interleukin-4 (IL-4) inhibited the response of CD8+ T cells and promoted the response of the CD4 subset. IL-2 or IL-7 was effective in increasing melanoma-specific cytotoxic T lymphocyte (CTL) activity in cultures where CD8 T cells were predominant, whereas IL-4 followed by IL-2 was most effective in cultures where CD4 T cells predominated. IL-10 or IL-12 inhibited proliferation and CTL activity against melanoma in long-term cultures. The effects of IL-12 were reproduced in long-term cultures of T cells stimulated with mAb against CD3 and were shown to depend on prior exposure of T cells to IL-12 before IL-2. As yet unidentified factors, such as co-factor expression on melanoma, appear to be as important as exogenous cytokines in determining the nature of T cell responses to melanoma. These results suggest that analysis of responses in long-term culture may assist in defining the role of key cytokines and other determinants of immune responses to melanoma.

CD4-Positive T-Lymphocytes↗
PubMed1997

Isolation and long-term culture of gallbladder epithelial cells from wild-type and CF mice.

Mice with targeted disruption of the cftr gene show pathophysiologic changes in the gallbladder, which correlate with hepatobiliary disease seen in cystic fibrosis patients. As gallbladder epithelium secretes mucin, and as this epithelium consists of a relatively homogenous cell type, study of CFTR function in these cells would be beneficial to delineate the complex cellular functions of this protein. The size and anatomic location of the murine gallbladder makes such studies difficult in vivo. Therefore, the need exists for in vitro models of gallbladder epithelium. We describe a method to isolate and culture murine gallbladder epithelium from wild-type and CF mice. Cells were grown in a monolayer on porous inserts over a feeder layer of fibroblasts. These nontransformed cells can be successively passaged and maintain a well-differentiated epithelial cell phenotype as shown by morphologic criteria, characterized by polarized columnar epithelial cells with prominent microvilli and intercellular junctions. Organotypic cultures showed columnar cells simulating in vivo morphology. This culture system should be valuable in delineating cellular processes relating to CFTR in gallbladder epithelium.

Animals↗
PubMed1997

In vitro susceptibility of Plasmodium falciparum isolates in Vietnam to artemisinin derivatives and other antimalarials.

We performed in vitro drug susceptibility assays of ten Plasmodium falciparum isolates collected from Vict Nam in 1995. All isolates were found to be highly sensitive to artesunate, dihydro-artemisinin and artemisinin. They were also sensitive to quinine. All of them were resistant to chloroquine and mefloquine in vitro. This study provides the baseline estimates of in vitro susceptibility levels of the Vietnamese isolates to artermisinin and their derivatives because the data were collected soon after these drugs were introduced countrywide. It also describes some quantitative profiles of the in vitro response of other standard antimalarial drugs in Viet Nam, which is presently limited.

Animals↗
PubMed1997

Epicuticular wax variation in ecotypes of Arabidopsis thaliana.

Quantification of the epicuticular wax from the stems of 40 ecotypes of Arabidopsis thaliana showed a two-fold range in total wax load that was not correlated to known abiotic characteristics of the ecotype's origin of collection. Chemical analysis of these ecotypes revealed similar epicuticular wax profiles for all ecotypes except CT-1. In CT-1 the amount of 22 and 24 carbon length primary alcohols was increased by 16- and 8-fold, respectively, over that observed in the epicuticular wax averaged over all ecotypes.

Animals↗
PubMed1997

Age is not a limiting factor for radical radiotherapy in pelvic malignancies.

BACKGROUND AND PURPOSE: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. MATERIAL AND METHODS: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. RESULTS: Survival was comparable in each age group for prostate (P = 0.18), uterus (0.41), anal canal cancer (P = 0.6) and slightly better for the younger group of rectum cancer (P = 0.04). A total of 1722 acute and 514 late grade > or = 1 were recorded. Acute nausea/ vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P = 0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P = 0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P = 0.79). For the grade > 2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P = 0.06) nor trend (P = 0.13) between age-groups. CONCLUSION: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies.

Age Factors↗
PubMed1997

Simultaneous high-dose external irradiation and daily cisplatin in unresectable, non-metastatic adenocarcinoma of the pancreas: a phase I-II study.

BACKGROUND AND PURPOSE: Clinical trials have demonstrated that high dose radiation therapy and daily cisplatin (CDDP) could increase local control and survival in carcinoma from various sites. The present phase I-II study has combined high dose radiation therapy and daily CDDP at escalating dosages. METHODS: From August 1994 to December 1995, 23 patients with non-resectable carcinoma of the pancreas were enrolled in a phase I-II multicentric, pilot study to test the toxicity and the effectiveness of high dose radiotherapy and daily cisplatin (CDDP) at escalating dosages. A dose of 6 mg/sqm/day of CDDP was selected for the phase II step since no grade IV toxicity occurred in any patient in the phase I step. RESULTS: Toxicity was considered fairly acceptable. At the time of analysis, the 23 patients who entered the study had clear evidence of evolutive disease either locally or distantly in the liver. It is suggested that high dose radiotherapy (60 Gy continuously) and daily CDDP have little effect on local control of the tumor and survival, and only a moderate effect on pain. CONCLUSIONS: In unresectable, apparently non-metastatic cancers of the pancreas, there is an urgent need for new agents or new combinations of agents to be tested.

Adenocarcinoma↗
PubMed1997

Characterization of two distinct chloride channels in cultured dog pancreatic duct epithelial cells.

Cl- secretion by pancreatic duct epithelial cells (PDEC) regulates cellular HCO3- secretion, an important component of the exocrine pancreas. In cystic fibrosis, for example, impaired function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel results in decreased pancreatic secretion and secondary pancreatic insufficiency. Studies of ion transport by PDEC have been hindered by the lack of a practical in vitro model. We have successfully cultured nontransformed dog PDEC on Vitrogen-coated permeable membranes overlying a feeder layer of myofibroblasts and report the characterization of Cl- channels in these cells. Cl- conductance, assessed through efflux of 125I from PDEC, was stimulated by agents acting via adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+. The Cl- conductances activated by cAMP and Ca2+ were distinct, since they were differentially inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and, to a lesser extent, by 5-nitro-2-(3-phenylpropylamino)benzoic acid and diphenylamine-2 carboxylate. Patch-clamp studies confirmed the presence of Cl- channels activated by cAMP and Ca2+, with differential inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The presence of CFTR Cl- channels in PDEC was confirmed by immunoblotting. These cultured PDEC are an optimal model for studies of pancreatic duct secretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product.

Studies of the effects of glucocorticoid (GC) and oxidative stress stimuli in differentiated cultures of human trabecular meshwork (HTM) cells have provided the rationale for our studies of a major new gene termed TIGR (trabecular meshwork inducible GC response). The TIGR clone was isolated by differential library screening using selection criteria based on the induction pattern of a new protein/glycoprotein found in HTM cultures after prolonged but not brief exposure to GCs. This GC induction pattern matched the time course and dose response required for intraocular pressure elevation in patients receiving corticosteroids. The very large, progressive induction of TIGR combined with specific structural features of its cDNA suggested that TIGR should be considered a candidate gene for outflow obstruction in glaucoma. Among the properties of TIGR cDNA were a signal sequence for secretion, several structural features for interactions with glycosaminoglycans and other glycoproteins and putative sites for cell surface interactions. In addition, the leucine zippers in the structure were related to TIGR-TIGR oligomerization that was shown to occur with native and recombinant TIGR protein. The verification that TIGR was a major stress response protein in HTM cells following hydrogen peroxide (or phorbol esters) exposure provided a potential link between GC and oxidative mechanisms thought to be involved in glaucoma pathogenesis. Pharmacological evaluation showed that basic fibroblast growth factory and transforming growth factor beta decreased the GC induction of TIGR, and certain nonsteroidal anti-inflammatory drugs protected against both GC- and oxidation-induced stress responses in HTM cells. Our recent studies of TIGR's genomic structure have shown motifs in the promoter region that suggest a basis by which multiple hormonal/environmental stimuli can regulate TIGR production and by which putative genetic alterations could lead to an overexpression of the protein. Further application of cell biology/biochemistry, molecular biology, genetic and histological approaches will be helpful in understanding the role of TIGR in different glaucoma syndromes.

Aged↗
PubMed1997

Ultraviolet radiation, melanocytic naevi and their dose-response relationship.

Melanocytic naevi on the face and neck of 110 Brisbane secondary school students aged 16-17 years were mapped according to specified regions to investigate the dose-response relationship between ultraviolet (UV) radiation and melanocytic naevi. Highest naevus density occurred in regions receiving a mean UV dose of 0.2-0.4 relative to the vertex while densities were low in minimally and maximally exposed regions. This pattern of naevus distribution was unaffected by sex or phenotypic features such as skin colour or degree of freckling. These findings suggest that there is a narrow dose range over which UV radiation can effectively promote the proliferation of melanocytes. A comparison of the regional distribution of naevi on the face and neck with that of solar keratoses appearing over 1 year on the heads of residents of a neighbouring town has shown them to differ significantly. This study may shed some light on the unknown, yet expectedly complex, relation of UV radiation to melanocytic naevi.

Adolescent↗
PubMed1996

Advanced carcinoma of the larynx: results of surgery and radiotherapy without induction chemotherapy (1980-1985): a multivariate analysis.

PURPOSE: Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patients who are complete responders. To clarify the treatment policies, a retrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival. METHODS AND MATERIALS: Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50-65 Gy according to nodal involvement and surgical margins status. RESULTS: The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients still alive with no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival. CONCLUSIONS: Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systematic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.

Adult↗
PubMed1996

Insulin modulation of newly synthesized apolipoproteins B-100 and B-48 in human fetal intestine: gene expression and mRNA editing are not involved.

We investigated insulin's effect on intestinal lipid, transport and, particularly, the biogenesis of apolipoproteins crucial to lipoprotein secretion. Adding insulin (3 mU) to the serum-free medium of cultured jejunal explants from human fetuses (17-20 weeks) reduced triglyceride and chylomicron production and inhibited apo B-48 and apo B-100 secretion. When apo B mRNA was assayed by RT-PCR and its editing by primer extension, no change was detectable following the addition of insulin. HDL lipid content, apo A-1 synthesis and RNA level were unaffected by insulin. Collectively, these results suggest that the insulin-stimulated decline in intestinal chylomicron output may involve apo B co- or post-translational modifications.

Abortion, Induced↗
PubMed1996

Detection of Toxoplasma gondii tachyzoites and bradyzoites in blood, urine, and brains of infected mice.

Different techniques for identifying Toxoplasma gondii were compared. PCR was used to amplify part of the major surface antigen P30 gene of T. gondii. Amplified-DNA detection with the DNA enzyme immunoassay (PCR-DEIA) was more sensitive than ethidium bromide staining after agarose gel electrophoresis and as sensitive as nested PCR. PCR-DEIA, using common enzyme-linked immunosorbent assay (ELISA) methods, avoids agarose gel electrophoresis for the identification of amplified products. T. gondii can also be detected with equal sensitivity in infected fibroblasts, but only after at least 8 days of cell culture. PCR-DEIA is thus recommended because of its sensitivity and convenience for detecting early parasitemia in the surveillance of toxoplasmosis among pregnant women and immunocompromised hosts. The courses of infection in mice infected with two strains of T. gondii were compared. Tachyzoites of the virulent strain T. gondii RH, killing the host in 4 days, were identified in urine specimens and blood samples of mice 24 to 94 h after inoculation but not in brains, but no antibodies were detected. After intraperitoneal inoculation with cysts of the low-level virulence Beverley strain of T. gondii, parasites were identified in blood samples 4 days later and up to 17 days (but not in urine specimens) and in the brain from day 6 through day 525. By ELISA, high antibody titers were found from day 11 to day 525, with parasitemia preceding the appearance of antibodies. The usefulness of PCR-DEIA tests in conjunction with the search for circulating antibodies for the early diagnosis of toxoplasmosis in humans is discussed.

Animals↗
PubMed1996

Sequence variation in the 18S rRNA gene, a target for PCR-based malaria diagnosis, in Plasmodium ovale from southern Vietnam.

Field surveys of malaria were performed in southern Vietnam by using an acridine orange staining method for rapid diagnosis and a PCR-based, microtiter plate hybridization method for accurate diagnosis. A total of three patients of Plasmodium ovale infection were detected, but PCR-amplified DNA of the P. ovale isolates from two of the patients did not hybridize with the P. ovale-specific probe. Analysis of the target sequence in the 18S rRNA gene indicated that in the DNA of isolates from both patients three nucleotides in the probe region from the typical P. ovale sequence were different, with deletions of two nucleotides and the substitution of one nucleotide. These results may suggest that in addition to molecular biological methods, careful microscopic examination of stained thin blood films is still required in studies of the prevalence of different malaria species.

Animals↗