Pulmonary renal syndrome and thrombotic thrombocytopenic purpura in a patient with giant cavernous hemangioma of the leg.
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Anti-Glomerular Basement Membrane Disease↗
Biomedical subjects
S C Tang
Publications and source records attributed to S C Tang.
Epoetin alfa therapy increases hemoglobin levels and improves quality of life in patients with cancer-related anemia who are not receiving chemotherapy and patients with anemia who are receiving chemotherapy.
PURPOSE: To evaluate efficacy, safety, and quality of life (QOL) changes with epoetin alfa therapy for anemia in patients with nonmyeloid malignancies. PATIENTS AND METHODS: Anemic cancer patients were enrolled onto this prospective, open-label study from 34 centers across Canada. The trial had two cohorts: patients who were and were not receiving chemotherapy during the 16-week study. All patients initially received epoetin alfa 150 IU/kg subcutaneously three times per week. The dose was doubled after 4 weeks for patients who did not experience sufficient response. RESULTS: Of the 183 patients enrolled in the nonchemotherapy cohort, statistically significant and clinically relevant improvements in QOL were observed with epoetin alfa therapy using both the FACT-An questionnaire and linear analog scale assessment. Hemoglobin levels increased significantly (P <.001; mean increase 2.5 g/dL from baseline to end of study) and these increases were positively correlated with improved QOL and change in Eastern Cooperative Oncology Group (ECOG) scores. There was a significant reduction in the percentage of patients who required blood transfusions. The 218 patients in the chemotherapy cohort also experienced significant improvements in QOL, decreased transfusion use, and increased hemoglobin levels that correlated with QOL improvements and change in ECOG scores. Epoetin alfa was well-tolerated in both cohorts. CONCLUSION: Epoetin alfa administered to patients with cancer-related anemia for up to 16 weeks resulted in significantly improved QOL, increased hemoglobin levels, and decreased transfusion use. These benefits were observed in cancer patients who were not receiving chemotherapy as well as those who were.
Aged↗
Prognostic significance of BAG-1 expression in nonsmall cell lung cancer.
The purpose of this study was to evaluate the expression of BAG-1 in a cohort of patients with nonsmall cell lung cancer (NSCLC). The intensity and subcellular distribution of BAG-1 expression were correlated with overall survival. Tumor samples were collected from 85 patients diagnosed with NSCLC between 1993-1995 in St. John's, Newfoundland. Expression of BAG-1 was determined by immunohistochemistry using polyclonal anti-BAG-1 antibody. There was significant variation in the immunohistochemical staining patterns of BAG-1, including nonstaining and staining of either the cytoplasm, nucleus or both. Univariate Cox regression analysis showed that those patients whose tumor overexpressed BAG-1 had a significant reduction in the risk of death (hazard ratio = 0.53, p = 0.03). The survival advantage of patients with BAG-1 overexpression tumor was also demonstrated by Kaplan-Meier analysis and log-rank tests (median survival 30.10 months versus 17.04 months, p = 0.05). In addition, multivariate Cox regression analysis showed that patients whose tumor exhibited intense cytoplasmic staining had a further reduction of the risk of death (hazard ratio = 0.42, p = 0.03) and this effect was independent of age, stage and histology. All stages were included in the analysis. Our preliminary data strongly indicate that further investigation is warranted to better define the role of BAG-1 as an independent prognostic factor in NSCLC.
Adult↗
BAG-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway.
Human BAG-1 is an anti-apoptotic protein with four protein isoforms (BAG-1 p50, p46, p33, and p29). BAG-1 p46 was originally isolated in a screen for proteins binding to the glucocorticoid receptor; it binds and modulates the action of several members of the nuclear steroid hormone receptor superfamily. The vitamin D receptor (VDR) is another member of this superfamily, and the vitamin D pathway is important for prevention and therapy of osteoporosis, renal failure, cancer, and psoriasis. Therefore, we investigated the effect of the recently isolated BAG-1 p50 on the vitamin D pathway. By use of Far Western blot analysis and glutathione S-transferase BAG-1 p50 binding assays, BAG-1 p50 was demonstrated to interact with the VDR, and the BAG-1 p50 N-terminus was required. In U87 cells that were stably transfected with BAG-1 p50, binding of the VDR to its response element in electrophoretic mobility shift assays was blocked, enhancement of transcriptional activation was inhibited, cell growth rate was enhanced, cell growth inhibition induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was blocked, and 1,25(OH)2D3-mediated VDR induction was inhibited. These results suggest that BAG-1 p50 is a novel regulator of the vitamin D signaling pathway, and its overexpression may lead to cellular resistance to 1,25(OH)2D3 therapy.
Calcitriol↗
Increased survival of mesothelial cells from the peritoneum in peritoneal dialysis fluid.
Peritonitis remains the most important factor in patient morbidity and technical failure associated with continuous ambulatory peritoneal dialysis (CAPD). In vitro examination of bacterial infection of cultured human peritoneal mesothelial cells (HPMC) is an attractive approach to the study of peritonitis in CAPD, yet there are few reports on this subject. Previous studies have shown two limitations: (i) cell cultures of HPMC lasted for days only when incubated in culture medium and (ii) short-term studies of <30 min were done in HPMC when incubated with peritoneal dialysis fluid (PDF). Human peritoneal mesothelial cells, maintained in a conventional single chamber culture system with PDF alone, were unable to survive more than 40 min. The present study was designed to prolong the viability of HPMC cultured in PDF, with the object of using cells under different conditions, such as that of simulating CAPD. HPMC were cultured using plastic microtiter plates, where they were grown to confluence and growth was arrested. PDF containing different concentrations of NaHCO3and human serum albumin was added. Cell viability after exposure for up to 24 h was measured by trypan blue, Cell Death Detection ELISA and Annex-V flow cytometry. The data confirmed the 'toxic' effect of PDF, with cell viability being <40% after 2 h incubation in 4.25% glucose in PDF. However, the survival time of HPMC increased significantly in 4.25% glucose PDF at a physiological pH and even further after the addition of human albumin. These experimental conditions simulating CAPD may allow future in vitro studies of mesothelial physiology and peritonitis related to CAPD treatment.
Cell Culture Techniques↗
Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death.
Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low level induced apoptosis or programmed cell death (PCD) in the Bcl-2 low-expressing K562 human erythroleukemia cells, and that a high level induced blister cell death (BCD); whereas Bcl-2 overexpressing, sanguinarine-treated JM1 pre-B lymphoblastic cells displayed neither apoptosis nor BCD morphologies. Here, we report that sanguinarine-treated K562 cells, when analyzed by western blot, showed significant increase in expression of the pro-apoptotic Bax protein in apoptosis, but not in BCD. cDNA expression array of PCD in K562 cells failed to reveal the presence of Bax at the gene transcript level, which suggests that this cell death process does not require de novo protein synthesis. Treated JM1 cells, on the other hand, showed an increase in the expression of Bcl-2 protein in both forms of cell death, but failed to show Bax expression. The role of other members of the Bcl-2 family remained negligible. Caspase-3 activation was observed in apoptosis of K562 cells but not in BCD or in sanguinarine-treated JM1 cells. These results suggest that sanguinarine in K562 cells induces apoptosis through increasing Bax and activating caspase-3, whereas sanguinarine-induced BCD involves neither. These results also suggest that in JM1 cells, Bcl-2 may play a role in susceptibility of cells to induction of apoptosis and BCD.
Alkaloids↗
Isolated vagus nerve palsy probably associated with herpes simplex virus infection.
Vagus nerve palsy caused by herpes simplex virus (HSV) infection is rare. Here, we present a 29-year-old man with acute onset of right side otalgia and sore throat, followed by dysphonia, dysphagia and some vesicles seen on the deep soft palate. Laryngoscopy revealed right vocal cord palsy. Neck to chest CT did not reveal local lesion. Three months later, his serum HSV IgG antibody titer was eight times elevation and a throat swab culture for virus isolation yielded HSV type I. T2-weighted images of neck MRI showed abnormally high signal intensity on the right sub-glottis region with Gadolinium enhancement that was compatible with local infection. Thereafter, one course of acyclovir; was given. Three months after finishing the acyclovir, his symptoms were almost gone and neck MRI did not show the aforementioned lesions. HSV infection should be considered as a differential diagnosis for patients with idiopathic dysphonia and dysphagia.
Acyclovir↗
Charge-dependent binding of polymeric IgA1 to human mesangial cells in IgA nephropathy.
BACKGROUND: IgA nephropathy (IgAN) is characterized by raised serum IgA1 and predominant mesangial IgA1 deposits of polymeric nature. The mechanism of polymeric IgA1 (pIgA1) deposition in the kidney mesangium is poorly understood in IgAN. It has been suggested that increased sialic acid content and anionic charge of the pIgA1 molecules may be operational in the IgA1 deposition in human mesangial cells (HMCs). The present study examined the binding of pIgA1 with different surface charges to HMCs. The binding characteristics of IgA1 to HMCs in the presence of polycation (poly-L-lysine) or polyanion (heparin) were also investigated. METHODS: IgA1 was purified in sera from patients with IgAN and from healthy controls by jacalin affinity chromatography. IgA1 was further separated into pIgA1 and monomeric IgA1 (mIgA1) by fast protein liquid chromatography (FPLC). pIgA1 or mIgA1 with different net charges on their surface were resolved by ion exchange chromatography (IEC) with a Mono Q column. The binding characteristics of pIgA1 and mIgA1 to HMCs in the presence or absence of polycation or polyanion were examined by flow cytometry. RESULTS: In patients with IgAN, the absolute amount of mIgA1 and pIgA1 is significantly higher than that of healthy controls (P < 0. 001). There was significant increase in binding of pIgA1 from patients with IgAN to HMC and cell lysate. pIgA1 that interacted strongly with the ion exchanger also bound more to HMCs when compared with IgA1 interacted weakly with the ion exchanger (P < 0. 001). The anionic charged pIgA1 from patients was significantly higher than that of healthy controls (P < 0.001). Preincubation with poly-L-lysine increased the binding of pIgA1 to HMCs. The binding of pIgA1 to HMCs was decreased by preincubation with heparin. CONCLUSIONS: The binding of IgA to HMCs is charge dependent. Polymeric IgA with the highest net negative charge binds more to HMCs. Preincubation with polyanion decreased the binding of polymeric IgA to HMCs. These results suggest an important role for anionic charge in IgA1 deposition onto the kidney mesangial cells.
Adult↗
Sanguinarine induces bimodal cell death in K562 but not in high Bcl-2-expressing JM1 cells.
Our previous studies with low Bcl-2-expressing K562 cells have shown that, when treated with the putative anti-cancer drug sanguinarine, concentrations of 1.5 microg/ml induced the morphology of apoptosis or programmed cell death (PCD), while concentrations of 12.5 microg/ml induced a morphology of blister formation or blister cell death (BCD). To elucidate the possible role of Bcl-2 in this dual cell death modality induced by sanguinarine, K562 and the high Bcl-2-expressing JM1 cells were treated with sanguinarine concentrations of 1.5 microg/ml and 12.5 microg/ml respectively, and multiple parameters of their effects were studied using light and electron microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling, 51Cr release, trypan blue exclusion, propidium iodide exclusion, and annexin-V binding. In general, we found that, while K562 cells underwent PCD and BCD when treated with sanguinarine, JM1 cells failed to undergo either PCD or BCD under the same experimental conditions. Thus, the over-expression of anti-apoptotic Bcl-2 may have prevented sanguinarine from inducing PCD and BCD in JM1 cells. These results indicate that the resistance of JM1 cells to the alkaloid sanguinarine may have been due to an anti-BCD role played by Bcl-2, in addition to its widely reported anti-apoptotic role.
Alkaloids↗
Human papillomavirus type 16-immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype.
Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is a highly effective chemotherapeutic agent against cervical cancer, but drug resistance is a major obstacle in its clinical application. The mechanism of drug resistance in human cervical cancer is not well understood. Here, we established an in vitro endocervical, cisplatin-resistant cell system that mimics the development of cisplatin resistance in the human cervix. Human papillomavirus (HPV) type 16-immortalized human endocervical cells (HEN-16-2) were treated with cisplatin, and the cisplatin-selected cells (HEN-16-2/CDDP) were resistant to cisplatin, paclitaxel, actinomycin D, doxorubicin, etoposide, and 5-fluorouracil, thus demonstrating a multidrug resistance (MDR) phenotype. Furthermore, compared with a similar passage of drug-sensitive HEN-16-2 cells, HEN-16-2/CDDP cells exhibited the general growth characteristics of cancer cell lines: faster growth in medium containing serum and high calcium levels, higher saturation density, anchorage-independent growth, and formation of tumors in nude mice. These results provided the first in vitro evidence that cisplatin selection can transform HPV-immortalized endocervical cells and cause a phenotype of MDR.
Animals↗
Resistance to apoptosis is correlated with the reduced caspase-3 activation and enhanced expression of antiapoptotic proteins in human cervical multidrug-resistant cells.
Recent studies have indicated that induction of apoptosis is the primary cytotoxic mechanism of most cancer chemotherapeutic agents, and abnormalities in the control of apoptosis can affect the sensitivity of malignant cells to multiple drugs. Here, we treated cells with cisplatin and other apoptotic stimuli and found that multidrug-resistant (MDR) endocervical HEN-16-2/CDDP cells, compared with drug-sensitive parental cells, were significantly more resistant to apoptosis and exhibited decreased proteolytic activation of caspase-3. The latter was further demonstrated by decreased cleavage of its substrate poly(ADP-ribose) polymerase (PARP). Further, Western blot analysis showed that MDR HEN-16-2/CDDP cells had significantly higher levels of the apoptosis-inhibiting proteins BAG-1 p50 and p33 isoforms and Bcl-X(L). This study provided the first evidence that overexpression of antiapoptotic BAG-1 p50 and p33 and Bcl-X(L) may cause resistance to apoptosis through reduction of caspase-3 activity in human cervical cells having an MDR phenotype.
Acetyltransferases↗
Safety, feasibility, and efficacy of a resistance training program in preadolescent obese children.
BACKGROUND: Safe and effective exercise programs are needed to prevent and treat chronic diseases in childhood. In particular, preadolescent obese children should participate in activities that are specific to their special needs. Resistance or strength training has been prescribed for adult obese persons. Research is limited concerning the use of resistance training in programs that treat obese preadolescents. METHODS: Nineteen treatment subjects (7-12 years of age) were enrolled in a 10-week weight management program which included diet, behavior modification, and aerobic and flexibility exercises. Forty-eight control subjects (7-12 years of age) participated in the diet, behavior modification program, and a thrice-a-week walking program. The efficacy of the overall weight management program was examined by anthropometry at 10 weeks and 1 year. RESULTS: Fifteen treatment subjects completed the 10-week program (retention rate, 78.9%). Thereafter compliance decreased by approximately 33% for the long-term study. Seventeen control subjects completed the program (retention rate, 35%). Weight, percent of ideal body weight, and body mass index were reduced significantly at 10 weeks (P<0.0001) and did not increase significantly at 1-year follow-up in both treatment and control groups. Height increased significantly at 1 year in both treatment and control subjects. In the treatment subjects, percent fat decreased significantly (P<0.001), whereas fat-free mass did not change significantly (P>0.05). CONCLUSIONS: A resistance-training program may be included safely in a multidisciplinary weight management program for obese preadolescent male and female children. The addition of specific exercise regimes such as resistance training may improve program retention especially in severely obese youth.
Body Mass Index↗
Tuberculous peritonitis in patients on continuous ambulatory peritoneal dialysis.
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Antitubercular Agents↗
Cloning and characterization of the human BAG-1 gene promoter: upregulation by tumor-derived p53 mutants.
BAG-1 is an anti-apoptotic protein that interacts with Bcl-2, Bcl-XL, Hsp70/Hsc70, Raf-1 and numerous hormone or growth factor receptors. Recently, BAG-1 has been found to be overexpressed in a variety of human cancer cell lines and some tumors. However, the molecular mechanism of BAG-1 upregulation is still unclear. In this study, we cloned 0.9 kb of human genomic DNA, BGEV, 5' flanking the BAG-1 open reading frame. BGEV subcloned into a promoterless luciferase reporter vector conferred high promoter activity in various human cancer cell lines. Deletion analysis of this sequence localized the region of maximal BAG-1 promoter activity from nucleotide positions -353 to -54, upstream of the first start codon CTG. Sequence analysis of the BAG-1 promoter region showed the absence of a TATA box but identified a CCAAT box, several GC boxes, a CpG island and several transcriptional factor binding sites, which may be important in the regulation of BAG-1 transcription. Most importantly, functional characterization of the BAG-1 promoter in vivo demonstrated that gain-of-function p53 mutants derived from human tumors upregulated the transcription of BAG-1 RNA and the expression of a reporter gene from the BAG-1 promoter. These results indicated that we have isolated the functional constitutive BAG-1 promoter. Furthermore, the data suggested that overexpression of BAG-1 in some tumors may be due to upregulation of the human BAG-1 promoter by mutant p53.
Base Sequence↗
Overexpression of anti-apoptotic gene BAG-1 in human cervical cancer.
Apoptosis is a programmed cell death process in which cells commit suicide under certain environmental conditions. Recent studies suggest that apoptosis is controlled by a variety of cellular genes, and dysregulation of these genes plays an important role in the pathogenesis of human diseases, including cancer. BAG-1 is a novel anti-apoptotic protein isolated by its interaction with another anti-apoptotic protein, Bcl-2. It binds to several hormone receptors and growth factor receptors and modulates their function in apoptosis. However, the role of BAG-1 in the oncogenesis of human cervical cancer has yet to be illustrated. In this study, we examined the expression of BAG-1 in cervical normal and carcinoma cultured cells and tissues. BAG-1 was overexpressed in human cervical carcinoma cell lines and tissues. Overexpression was regulated at the transcriptional level. The increased expression of BAG-1 was correlated with enhanced resistance of cervical carcinoma cells to apoptosis induced by a DNA-damaging reagent. In addition, overexpression of BAG-1 enhanced the resistance of cervical cells to apoptosis. This study provided the first evidence that BAG-1 is upregulated in human cervical cancer and may play an important role in apoptosis and human cervical carcinogenesis.
Apoptosis↗
Inclusion of resistance exercise in a multidisciplinary outpatient treatment program for preadolescent obese children.
BACKGROUND: Safe and effective exercise programs are needed to prevent and treat chronic diseases in childhood. In particular, preadolescent obese children should participate in activities that are specific to their special needs. METHODS: We included a moderate intensity, progressive resistance training program in a multidisciplinary weight management program for obese preadolescent children. The program included diet, behavior modification, and aerobic and flexibility exercises. RESULTS: The subjects reported no accidents or injuries and 100% compliance with the minimum required exercise prescription. Weight, percent ideal body weight, body mass index, and percent fat were reduced significantly at 10 weeks and did not increase significantly at 1 year follow-up. Height and lean body mass increased significantly at 1 year. CONCLUSION: A resistance training program may be safely included in a multidisciplinary weight management program for obese preadolescent children.
Adolescent↗
Expression of BAG-1 in invasive breast carcinomas.
PURPOSE: The purpose of this study was to retrospectively evaluate the expression of BAG-1 in invasive breast carcinomas. The intensity and subcellular distribution of BAG-1 expression was correlated with conventional prognostic factors and with disease-free and overall survival. PATIENTS AND METHODS: One hundred forty patients diagnosed with invasive breast cancer in St. John's, Newfoundland, between 1986 and 1996 were included in the study. The median follow-up of the study was 8 years. Expression of BAG-1 was determined by immunohistochemical staining of paraffin-embedded breast tumor tissues. RESULTS: Of the 140 breast carcinomas examined, 77.1% were positive for BAG-1 expression. Except for differentiation, no correlation was observed between BAG-1 expression and conventional prognostic factors such as age, histology, stage, and estrogen and progesterone receptor status. In multivariate analysis, BAG-1 expression was significantly associated with shorter disease-free (P =.0052) and overall survival (P =.0033). Patients whose tumors expressed nuclear BAG-1 tended to have a shorter disease-free (63 v 84 months; P = 0.4493) and overall (69 v 99 months, P =.1009) survival. CONCLUSION: BAG-1 is overexpressed in the majority of invasive breast carcinomas. Although BAG-1 did not correlate with conventional prognostic factors, its overexpression, especially the nuclear expression, may be associated with a shorter disease-free and overall survival. Our preliminary data strongly indicate that further investigation is warranted to define the role of BAG-1 as an independent prognostic factor in patients with newly diagnosed breast cancer.
Adult↗
Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency.
5-Fluorouracil (5-FU) is an analogue of pyrimidine nucleosides that is widely used in the treatment of head and neck, breast, ovarian, and colon cancer. Stomatitis, diarrhea, dermatitis, and myelosuppression are the main toxicities of 5-FU. A less frequent side effect that is becoming more recognized is neurologic toxicity. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU. DPD deficiency follows an autosomal recessive pattern of inheritance, and its prevalence is estimated to be 3%. Cancer patients who are receiving 5-FU treatment and are DPD deficient can develop severe side effects. The neurologic toxicity can vary from being mild to severe and prolonged. We describe the side effects of 5-FU in a colon cancer patient who suffered severe mucositis, desquamating dermatitis, prolonged myelosuppression, and neurologic toxicity that required admission to the intensive care unit. The patient remained hospitalized for 3 months. Recovery from the side effects was complete 4 months after the last 5-FU treatment. Subsequent testing revealed that this patient has an extremely low level of DPD activity (0.015 nmol/min/mg protein; mean, 0.189 nmol/min/mg protein). Because neurologic toxicity is becoming more recognized and DPD affects the catabolism of 5-FU, we discuss management issues and the use of new DPD inhibitors. We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.
Colonic Neoplasms↗