Biomedical subjects

C H Yang

Publications and source records attributed to C H Yang.

At least 73 records · Page 4Linked to original sources

PubMed2000

Pharmacokinetics of the fluocinolone/5-fluorouracil codrug in the gas-filled eye.

PURPOSE: To determine the effect of intraocular gas tamponade on drug levels achieved with the intravitreal sustained-release fluocinolone (FL)/5-fluorouracil (5-FU) codrug pellet. METHODS: After insertion of a 10-mg codrug pellet into the right eyes of 43 New Zealand white rabbits, perfluoropropane (0.4 mL of 100% C3F8) or a control sham was then injected into the midvitreous cavity. On postoperative days 2, 4, 7, 21, and 42, aqueous samples were collected, the rabbits were killed, and the right eyes were enucleated. The vitreous and remaining codrug pellet were then isolated. Pellet and intravitreal drug levels were determined by high-pressure liquid chromatography. RESULTS: No measurable drug levels were detected in any of the aqueous samples. Maximal gas expansion occurred by day 4 and partial resorption was observed by days 14 to 21. Vitreous FL and 5-FU levels during C3F8 expansion (day 2) were statistically significantly higher in the gas-filled eyes. On postoperative days 4, 7, 21, and 42, there were no statistically significant differences between FL and 5-FU drug levels in eyes containing C3F8 as compared with control eyes. Pellet codrug, FL, and 5-FU levels over time were similar in gas-filled and control eyes. CONCLUSIONS: Intraocular gas tamponade does not significantly affect the sustained intravitreal drug levels achieved with the FL/5-FU codrug. If clinically efficacious, the FL/5-FU codrug formulation does not need to be altered to treat proliferative vitreoretinopathy in the presence of intraocular gas.

Animals↗

PubMed2000

Structural changes in alpha-synuclein affect its chaperone-like activity in vitro.

Alpha-synuclein, a major constituent of Lewy bodies (LBs) in Parkinson's disease (PD), has been implicated to play a critical role in synaptic events, such as neuronal plasticity during development, learning, and degeneration under pathological conditions, although the physiological function of alpha-synuclein has not yet been established. We here present biochemical evidence that recombinant alpha-synuclein has a chaperone-like function against thermal and chemical stress in vitro. In our experiments, alpha-synuclein protected glutathione S-transferase (GST) and aldolase from heat-induced precipitation, and alpha-lactalbumin and bovine serum albumin from dithiothreitol (DTT)-induced precipitation like other molecular chaperones. Moreover, preheating of alpha-synuclein, which is believed to reorganize the molecular surface of alpha-synuclein, increased the chaperone-like activity. Interestingly, in organic solvents, which promotes the formation of secondary structure, alpha-synuclein aggregated more easily than in its native condition, which eventually might abrogate the chaperone-like function of the protein. In addition, alpha-synuclein was also rapidly and significantly precipitated by heat in the presence of Zn2+ in vitro, whereas it was not affected by the presence of Ca2+ or Mg2+. Circular dichroism spectra confirmed that alpha-synuclein underwent conformational change in the presence of Zn2+. Taken together, our data suggest that alpha-synuclein could act as a molecular chaperone, and that the conformational change of the alpha-synuclein could explain the aggregation kinetics of alpha-synuclein, which may be related to the abolishment of the chaperonic-like activity.

Albumins↗

PubMed2000

Rhizosphere microbial community structure in relation to root location and plant iron nutritional status.

Root exudate composition and quantity vary in relation to plant nutritional status, but the impact of the differences on rhizosphere microbial communities is not known. To examine this question, we performed an experiment with barley (Hordeum vulgare) plants under iron-limiting and iron-sufficient growth conditions. Plants were grown in an iron-limiting soil in root box microcosms. One-half of the plants were treated with foliar iron every day to inhibit phytosiderophore production and to alter root exudate composition. After 30 days, the bacterial communities associated with different root zones, including the primary root tips, nonelongating secondary root tips, sites of lateral root emergence, and older roots distal from the tip, were characterized by using 16S ribosomal DNA (rDNA) fingerprints generated by PCR-denaturing gradient gel electrophoresis (DGGE). Our results showed that the microbial communities associated with the different root locations produced many common 16S rDNA bands but that the communities could be distinguished by using correspondence analysis. Approximately 40% of the variation between communities could be attributed to plant iron nutritional status. A sequence analysis of clones generated from a single 16S rDNA band obtained at all of the root locations revealed that there were taxonomically different species in the same band, suggesting that the resolving power of DGGE for characterization of community structure at the species level is limited. Our results suggest that the bacterial communities in the rhizosphere are substantially different in different root zones and that a rhizosphere community may be altered by changes in root exudate composition caused by changes in plant iron nutritional status.

Bacteria↗

PubMed2000

Inhibition of ornithine decarboxylase induces STAT3 tyrosine phosphorylation and DNA binding in IEC-6 cells.

Polyamines are required for the proliferation of the rat intestinal mucosal IEC-6 cell line. Ornithine decarboxylase (ODC) is the enzyme that catalyzes the first step in polyamine synthesis. ODC inhibition not only leads to polyamine depletion but also leads to inhibition of cell proliferation and regulates the expression of the immediate-early genes c-fos, c-myc, and c-jun. Members of the signal transducers and activators of transcription (STAT) transcription factor family bind to the sis-inducible element (SIE) present in the promoters to regulate the expression of a variety of important genes. In the present study, we tested the hypothesis that the STAT3 transcription factor, which is responsible for activation of the acute phase response genes, is activated after inhibition of ODC. We found that inhibition of ODC rapidly induces STAT3 activation as determined by STAT3 tyrosine phosphorylation, translocation of STAT3 from the cytoplasm into the nucleus, and the presence of STAT3 in SIE-dependent DNA-protein complexes. STAT3 activation upon inhibition of ODC was accompanied by the activation of a STAT3-dependent reporter construct. Moreover, prolonged polyamine depletion resulted in downregulation of cellular STAT3 levels.

Animals↗

PubMed2000

Repetitive phenomena in dementia.

OBJECTIVE: Both repetitive talk and behaviors (repetitive phenomena) are common in demented patients and are bothersome to their caregivers and families. The purpose of this preliminary report was to explore these repetitive phenomena in demented patients admitted to a geropsychiatric ward. METHOD: The sample population consisted of 141 demented patients. Patients' caregivers were asked if patients had presented a repetitive fixed pattern of physical action or talk since the onset of dementia. RESULTS: Of the 141 demented patients included in the study, seventy-nine had repetitive phenomena. Patients with these phenomena had various presentations and developed them in the early stage of dementia. CONCLUSIONS: Repetitive phenomena are widespread in dementia, especially for older patients, and may be an early sign of dementia. The characteristics of repetitive phenomena and some likely underlying mechanisms are discussed.

Aged↗

PubMed2000

The clinical applications of Mini-Mental State Examination in geropsychiatric inpatients.

OBJECTIVE: This study investigated the association between Mini-Mental State Examination (MMSE) scores and diagnosis, computerized tomographic scans or electroencephalogram findings in geropsychiatric inpatients (age > or = 65). METHOD: We analyzed the MMSE records of patients sixty-five and older who had been hospitalized in our psychiatric ward during a nine-year period. Case data were collected by review of chart records. RESULTS: In these patients, MMSE scores were significantly different among the seven diagnostic groups included. Demented patients had the lowest MMSE scores. Patients who had abnormal findings on computerized tomographic scans or electroencephalogram had lower MMSE than patients with normal findings. CONCLUSION: Our findings suggest that the MMSE is a useful screening instrument for organicity in the geropsychiatric inpatients. However, because of the lower average MMSE score in geropsychiatric inpatients, the optimal cut-offpoint of MMSE for dementia should be lower than those used in other populations.

Aged↗

PubMed2000

Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: an useful salvage therapy.

Arsenic trioxide (As2O3) was recently identified as a very potent agent against acute promyelocytic leukemia (APL). Intravenous infusion of 10 mg As2O3 daily for one to two months can induce significant complete remission (CR) of APL, and there is no cross drug-resistance between As2O3 and other antileukemic agents, including all-trans retinoic acid (ATRA). The CR rate of relapsed and/or refractory APL patients who received As2O3 treatment ranged from 52.3% to 93.3%. The median duration to CR ranged from 38 to 51 days, with accumulative As2O3 dosage of 340-430 mg. Although most adverse reactions of As2O3 treatment were tolerable, certain infrequent but severe toxicities related to As2O3 were observed, including renal failure, hepatic damage, cardiac arrhythmia and chronic neuromuscular degeneration, which should be monitored carefully. As2O3 can induce partial differentiation and subsequent apoptosis of APL cells through degradation of wild type PML and PML/RAR alpha chimeric proteins and possible anti-mitochondrial effects. Like the treatment of ATRA in APL, early relapses from As2O3 treatment within a few months were not infrequently seen, indicating that rapid emerging resistance to As2O3 can occur. Nevertheless, the PML/RAR alpha fusion protein was reported to disappear in some APL patients who received As2O3, and who might earn long-survival. However, the follow-up is still too short to draw the conclusion. Intriguingly, it has been shown that As2O3 can also induce apoptosis of other non-APL tumor cells with clinical achievable concentrations. However, the detailed molecular mechanisms are not yet fully understood. Further studies regarding to the pharmacological characters, clinical efficacies, toxicities, apoptogenic mechanisms, and spectrum of anti-tumor activity of As2O3 are warranted.

Acute Kidney Injury↗

PubMed2000

A case of Klinefelter syndrome with retroperitoneal teratoma.

Klinefelter syndrome (KS) is often associated with various neoplasms, especially germ cell tumors. Mediastinum is the most favored site of extragonadal germ cell tumors with KS, which is somewhat different from those without KS. The retroperitoneal germ cell tumor in KS is very rare. A five-month-old boy with an abdominal mass was found to have a retroperitoneal tumor. After surgical removal, he was diagnosed to have mature cystic teratoma. Cytogenetic study of his peripheral lymphocytes revealed that his karyotype was consistent with KS. This case suggests that patients with KS might be at risk of having germ cell tumors in sites other than mediastinum. It also suggests that all cases with these tumors should be screened for the presence of karyotypic abnormalities, and it might help to assess the exact correlation between germ cell tumors and KS, and to treat them accordingly.

Humans↗

PubMed2000

HLA-DQB1 genotyping with simple automated DNA sequencing and single-strand conformation polymorphism analysis.

BACKGROUND AND PURPOSE: Accurate human leukocyte antigen (HLA) typing is important for matching donors and recipients of bone marrow transplantation. Because HLA is highly polymorphic, HLA genotyping is also a valuable tool in forensic identification of humans. The primary objective of this study was to establish a simple, rapid, and economic HLA analysis system suitable for use in forensic applications. METHOD: We used the primer pair DB130 and CH29 to amplify the HLA class II DQB1 gene by polymerase chain reaction (PCR). The nucleotide sequences of the PCR products were analyzed with an ABI Prism 377 automatic DNA sequencer, with the aid of its systematic analytical procedure. Some genotypes were confirmed by single-strand conformation polymorphism (SSCP) analysis. RESULTS: We identified 15 alleles and 37 genotypes from 86 Taiwanese subjects. The most frequent allele was 03011 (27.9%) and the most frequent genotype was 03011/03011 (15.1%). Statistical analysis showed that the allelic diversity was 0.862 and the power of discrimination was 0.948. CONCLUSIONS: The results of this study indicate that the combined use of automated sequencing with only one primer pair and SSCP provides a simple, rapid, and economic tool for analyzing the DQB1 gene. Compared with other sequencing methods that use a set of multiple primers, this method has two advantages. First, it is simpler and faster, because the HLAB1 genotype can be determined in a single PCR reaction. Second, the use of only one primer set obviates the need for preferential annealing of any one primer set.

Forensic Medicine↗

PubMed2000

Safety and pharmacokinetics of an intraocular fluocinolone acetonide sustained delivery device.

PURPOSE: To determine the safety and pharmacokinetics of an intraocular fluocinolone acetonide sustained drug delivery device. METHODS: Nonbiodegradable drug delivery devices containing 2 or 15 mg of a synthetic corticosteroid, fluocinolone acetonide, were constructed. The long-term in vitro release rates of these devices were determined in protein-free buffer or buffer containing 50% plasma protein. Fifteen-milligram devices were also implanted into the vitreous cavities of rabbit eyes. Intravitreal drug levels, the amount of drug remaining in explanted devices, and the release rate of explanted devices were determined over a 1-year time period. Drug toxicity was assessed over this same time period by slit lamp examination, indirect ophthalmoscopy, electroretinography, and histologic examination. RESULTS: The drug release rates for the 2-mg device, 1.9 +/- 0.25 microg/d, and for the 15-mg device, 2.2 +/- 0.6 microg/d, remained linear over the 6-month and 45-day testing period, respectively. The release rate increased by approximately 20% when devices were transferred from protein-free buffer to buffer that contained protein (P: < 0.0001). Vitreous levels remained fairly constant (0.10-0.21 microg/ml) over a 1-year period. No drug was present in the aqueous humor during this time period. Based on the device release rates, the predicted life span of the 2- and 15-mg devices are 2.7 and 18.6 years, respectively. There was no evidence of drug toxicity by clinical examination, electroretinography, or histologic examination. CONCLUSIONS: It is feasible to construct a nontoxic fluocinolone acetonide drug delivery device that reproducibly releases fluocinolone acetonide in a linear manner over an extended period. These devices show great promise in the treatment of ocular diseases such as uveitis, which are often managed with chronic corticosteroid therapy.

Animals↗

PubMed2000

Hand motion assessment and rehabilitation system.

Along with the rapid development of information technology, computers play an increasingly prominent and important role. One current trend is to use computers as instruments for physical rehabilitation. In this study, we introduce a new hand motion assessment and rehabilitation system. This system assesses a user's grip strength and records the sudden changes in air pressure through a circuit and A/D adapter. A PC interface transforms and saves the data in a data record file. The data is then compiled and combined with a patient's case history and keyed into a database as reference for clinical use. The system is highly efficient, cheap and convenient to use. Doctors can use it to monitor and analyze the progress of a rehabilitation program.

Athletic Injuries↗

PubMed1999

Active site determination of yeast geranylgeranyl protein transferase type I expressed in Escherichia coli.

The ram2 and cal1 genes encode the alpha and beta subunits of yeast geranylgeranyl protein transferase type I (GGPT-I), respectively. Arginine 166 of the beta subunit was changed to isoleucine (betaR166I), histidine 216 to aspartic acid (betaH216D), and asparagine 282 to alanine (betaN282A) by sequential PCR using mutagenic primers. The mutants were expressed under the same conditions as the wild-type and were assayed for GGPT-I activity. Wild-type yeast GGPT-I, alphaH145D, alphaD140N, betaR166I, betaH216D and betaN282A mutant GGPT-Is were partially purified by ammonium sulfate fractionation followed by a Q-Sepharose column. Characterization studies were performed using the active fraction of the Q-Sepharose column. In the chemical modification reactions, the catalytic activity of purified enzyme decreased in proportion to the concentration of modifying reagents, such as phenylglyoxal and diethyl pyrocarbonate (DEPC). Geranylgeranyl pyrophosphate (GGPP) protected the enzyme activity from the modification with phenylglyoxal. The measurement of GGPP binding to wild-type and five mutant GGPT-Is was performed by a gel-filtration assay. The binding of GGPP to the betaR166I mutant was low and the Km value for GGPP in the betaR166I mutant increased about 29-fold. Therefore, the results suggest a role for this arginine residue that directly influences the GGPP binding. The activity of the DEPC-modified GGPT-I was inhibited by 80% at 5 mM DEPC. The differential absorption at 242 nm may suggest that at this concentration the modified histidine residues were 1.5 mol per GGPT-I. The protein substrate, glutathione S-transferase fused undecapeptide (GST-CAIL) protected the enzyme from inactivation by DEPC, and the Km value for GST-CAIL in the betaH216D mutant increased about 12-fold. The trypsin digestion of [14C]DEPC-modified enzyme yielded a single radioactive peptide. As a result of the sequence of this radioactive peptide, the histidine 216 residue was assumed to be an essential part of binding of peptide substrate.

Alkyl and Aryl Transferases↗

PubMed1999

High dose tamoxifen plus cisplatin and etoposide in the treatment of patients with advanced, inoperable nonsmall cell lung carcinoma.

BACKGROUND: Tamoxifen sensitizes cancer cells to chemotherapeutic agents. High dose tamoxifen has been tested in the treatment of patients with melanoma and other cancers. The authors conducted a Phase II study of high dose tamoxifen plus cisplatin and etoposide for patients with advanced, inoperable nonsmall cell lung carcinoma. METHODS: Patients with Stage IIIB, Stage IV, or recurrent disease; good performance status; measurable lesions; and good organ function were eligible. Tamoxifen 150 mg/m2/day, divided into 4 doses, was given for 8 days. Cisplatin 60 mg/m2 was given on Day 4. Etoposide 60 mg/m2/day was given on Days 4-8. Patients were allowed to remain in the study until either intolerable toxicity was observed or disease progression occurred. RESULTS: Forty patients were accrued and received a total of 191 cycles of treatment. All patients were evaluable for response and toxicity. One patient had a complete remission and 14 had a partial remission (overall response rate, 37.5%). The median survival was 47 weeks. One-year survival was 44%. Increased thrombotic episodes were noted; all were clinically manageable. CONCLUSIONS: High dose tamoxifen can be administered safely in combination with cisplatin and etoposide to patients with advanced nonsmall cell lung carcinoma. Favorable response rates and survival times were obtained. The value of high dose tamoxifen in the treatment of patients with nonsmall cell lung carcinoma can be evaluated further in randomized Phase III studies.

Adult↗

PubMed1999

Thioureas differentially induce rat hepatic microsomal epoxide hydrolase and rGSTA2 irrespective of their oxygen radical scavenging effect: effects on toxicant-induced liver injury.

Thioureas have been employed as potent hydroxyl radical scavengers and also inhibit production of oxygen free radicals. The in vitro oxygen radical scavenging effect by N,N'-substituted thioureas including dimethylthiourea (DMT), diethylthiourea (DET), tetramethylthiourea (TMT) and diphenylthiourea (DPT) was assessed by the conversion of phi x-174 DNA from supercoiled DNA to the open circular form or to fragmented DNA. Addition of the N,N'-substituted thioureas to the incubation mixture significantly prevented a single strand breakage of phi x-174 DNA induced by autooxidation of benzenetriol. These thioureas were also effective in preventing degradation of phi x-174 DNA induced by autooxidation of benzenetriol in the presence of ferrous iron. In view of the in vitro radical scavenging effect by the thioureas and the role of reactive oxygen species in the induction of phase II detoxifying enzymes, expression of microsomal epoxide hydrolase (mEH) and rGSTA2 in response to these agents was investigated in the rat liver. Rats treated with each of the alkylthioureas exhibited marked increases of mEH and rGSTA2 mRNA levels with TMT being the most effective. DPT an arylthiourea, however, was minimally active in increasing the mRNAs. Time-course studies revealed that DMT, DET and TMT increased the mRNA levels to the greatest extent at 24 h after a single dose of treatment. The levels of mEH and rGSTA2 mRNA were elevated in a dose-dependent manner by the alkylthioureas. Immunoblot analysis showed that the alkylthioureas induced mEH and rGSTA2 proteins in the liver (0.6 mmol/kg per day, 3 days), which was consistent with the increases in the mRNA levels. DMT, DET or TMT enhanced CCl4-induced liver toxicity, as monitored by plasma aminotransferase activity, although each of the agents alone caused only slight increase in the alanine aminotransferase activity. In contrast to the effects of the alkylthioureas, DPT protected the liver against the toxicant-induced injury. All of the thioureas prevented decreases in the hepatic glutathione level by CCl4. Expression of cytochrome P450 2E1 and P450 2B1/2, which are implicated with metabolic activation of CCl4, was assessed after treatment with the thioureas. P450 2E1 and P450 2B1/2 were differentially induced by the alkylthioureas with the expression of P450 2E1 being inversely related with that of P450 2B1/2. These results showed that N,N'-substituted alkylthioureas were capable of inducing mEH and rGSTA2 in the liver with elevation of the mRNAs, that induction of mEH and rGSTA2 by these alkylthioureas might be mediated by production of the reactive oxygens derived from metabolic activation of the agents irrespective of their radical scavenging effect and that the agents rather enhanced toxicant-induced liver injury with the induction of P450 2E1 or P450 2B1/2.

Alanine Transaminase↗

PubMed1999

Expression of the recombinant Klebsiella aerogenes UreF protein as a MalE fusion.

Expression of the active urease of the enterobacterium, Klebsiella aerogenes, requires the presence of the accessory genes (ureD, ureE, ureF, and ureG) in addition to the three structural genes (ureA, ureB, and ureC). These accessory genes are involved in functional assembly of the nickel-metallocenter for the enzyme. Characterization of ureF gene has been hindered, however, since the UreF protein is produced in only minute amount compared to other urease gene products. In order to overexpress the ureF gene, a recombinant pMAL-UreF plasmid was constructed from which the UreF was produced as a fusion with maltose-binding protein. The MBP-UreF fusion protein was purified by using an amylose-affinity column chromatography followed by an anion exchange column chromatography. Polyclonal antibodies raised against the fusion protein were purified and shown to specifically recognize both MBP and UreF peptides. The UreF protein was shown to be unstable when separated from MBP by digestion with factor Xa.

Animals↗

PubMed1999

The use of multiplane transesophageal echocardiography to evaluate residual patent ductus arteriosus during video-assisted thoracoscopy in adults.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has emerged as an innovative and popular procedure for interruption of patent ductus arteriosus (PDA), while intraoperative transesophageal echocardiography (TEE) has proven to be an effective monitor in the evaluation of residual patency. Previous reports on the adequacy of surgical interruption of PDA under VATS and TEE are available for pediatric patients, but only limited information is available for adults with PDA. MATEIALS AND METHODS: Between August 1995 and October 1997, we monitored 35 adult patients undergoing PDA interruption via VATS with Hewlett-Packard color Doppler multiplane TEE throughout the procedure. The average PDA diameter was 10.2 +/- 1.8 mm. All the PDA were completely ligated. RESULTS: Thirty-two patients showed no ductal flow after double ligation. In the other three patients, residual flow was detected intraoperatively after double ligation, but it was quickly abolished by the third ligation. One patient showed faint ductal flow by transthoracic echocardiography at postoperative follow-up, but no reintervention was needed. CONCLUSIONS: Our study showed that, with the refinement of adult PDA interruption via VATS, intraoperative multiplane TEE provides higher resolution for direct evaluation of the entire course of PDA ligation without interrupting the surgical procedure and minimizes the incidence of complications.

Adult↗

PubMed1999

Edwardsiella tarda bacteraemia--complicated by acute pancreatitis and pyomyoma.

Edwardsiella tarda (E. tarda) has recently become recognized as a pathogen in humans. Here we report a new case of E. tarda bacteraemia complicated by acute pancreatitis and pyomyoma. A 46-year-old female came to our emergency room complaining of sudden onset of left upper quadrant pain and vomiting for the previous few hours after drinking three bottles of wine. An abdominal computed tomography (CT) scan revealed multiple biliary stones, acute pancreatitis with extensive inflammatory change, and a large uterine myoma. Fever, watery diarrhoea, and mild suprapubic discomfort with vaginal spotting were noted soon after admission. The patient's blood cultures yielded E. tarda and symptoms subsided after antibiotic therapy. Fever and severe suprapubic pain with rebound tenderness developed 12 days later. Repeat abdominal CT scan revealed an enlarged uterine myoma with central necrosis. The patient subsequently underwent anterior total hysterectomy and bilateral salpingo-oophorectomy, revealing a uterine myoma with infarction and abscess formation. The patient recovered uneventfully and was discharged 1 week later.

Acute Disease↗

PubMed1999

Arsenic trioxide sensitivity is associated with low level of glutathione in cancer cells.

Arsenic trioxide (As2O3) is a novel anticancer agent, which has been found to induce remission in acute promyelocytic leukaemic patients following daily intravenous administration. The therapeutic value of As2O3 in other cancers is still largely unknown. Cytotoxic tests in a panel of cancer cell lines showed that bladder cancer, acute promyelocytic leukaemic and gastrointestinal cancer cells were the most sensitive to As2O3 among 17 cell lines tested. Cellular glutathione (GSH) system plays an important role in arsenic detoxification in mammalian cells. Cancer cells that were intrinsically sensitive to As2O3 contained lower levels of GSH, whereas resistant cancer cells contained higher levels of GSH. On the other hand, there was no association of glutathione-S-transferase-pi or multidrug resistance-associated protein 1 levels with arsenic sensitivity in these cancer cells. Multidrug-resistant cancer cells that were cross-resistant to arsenic contained higher levels of GSH or multidrug-resistance-associated protein 1 than their drug-sensitive parental cells. Cancer cells become more sensitive to arsenic after depletion of cellular GSH with L-buthionine sulphoximine. We concluded that cellular GSH level is the most important determinant of arsenic sensitivity in cancer cells. Cellular GSH level and its modulation by buthionine sulphoximine should be considered in designing clinical trials using arsenic in solid tumours.

Antimetabolites, Antineoplastic↗