Search PubMed⌕ Search

Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1997

Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits.

Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.

Administration, Oral↗
PubMed1997

The human HNP36 gene is localized to chromosome 11q13 and produces alternative transcripts that are not mutated in multiple endocrine neoplasia, type 1 (MEN I) syndrome.

Multiple endocrine neoplasia, type 1 (MEN I), is an autosomal dominant syndrome of selected endocrine neoplasms whose causative gene, a suspected tumor suppressor, has been localized to chromosome 11q13, but has not been identified. Recently, the HNP36 cDNA was identified as a novel growth factor responsive gene of undetermined biological function that is expressed in the pituitary and parathyroid glands. In studies seeking the function of the HNP36 gene product, the gene was localized by fluorescence in situ hybridization within the 11q13 segment. Further analysis of radiation-reduced hybrid DNAs and chromosome 11-specific YAC clones established that the HNP36 gene is within 80 kb of D11S913, a marker tightly linked to the MEN1 gene. Consequently, the HNP36 gene was studied as a candidate for the MEN1 gene. The human HNP36 gene was cloned and determined to consist of 12 exons. Expression of the HNP36 gene from pituitary and parathyroid tissue and four patient tumors or lymphoblasts was confirmed by RT-PCR amplification of the coding sequences, and HNP36 transcripts were analyzed for mutations. All tissues expressed three HNP36 gene transcripts that result from alternative splicing and appear to encode related, but distinct, proteins. However, DNA sequence determination of the RT-PCR products from MEN I-associated tumors found no deletions and identified a single nucleotide difference that may be a polymorphism. Thus, mutations in the coding segments of the HNP36 gene are not the cause of the MEN I syndrome. Nevertheless, the assignment of the HNP36 gene to 11q13 and identification of new potential gene products provides a novel growth-regulated genetic candidate for other disorders whose genes map to this locus.

Alternative Splicing↗
PubMed1997

Clinical utility of long-term enalapril/diltiazem ER in stage 3-4 essential hypertension. Long-term Use of Enalapril/Diltiazem ER in Stage 3-4 Hypertension Group.

The use of angiotensin converting enzyme inhibitors and calcium channel blockers, as monotherapies and in combination, is common in the management of hypertension. Clinical studies have documented the augmentation of blood pressure reduction when these agents are combined compared with the individual agents, in short-term studies. In the present investigation, 93 patients with stage 3-4 essential hypertension, who successfully completed a short-term double-blind study, participated in a 40-week open-label treatment phase. The patients were maintained on their previous doses of enalapril/diltiazem ER (E/D) with or without additional antihypertensive medications. Doses of medication could be adjusted as necessary for blood pressure control. Of the 93 patients, 68% were male and 82% were white; they averaged 52.7 years of age and had a baseline mean sitting blood pressure (SiBP) of 167/111 mmHg. The use of E/D alone (n = 14) reduced mean SiBP by 14.5/14.4 mmHg from baseline, whereas the use of E/ D with other agents (n = 79) decreased it by 27/20.5 mmHg from baseline. E/D alone or in combination with other drugs was well-tolerated, and no serious adverse events were noted. This long-term open-label study demonstrated that the E/D combination alone or with the addition of other antihypertensive drugs was effective, safe, and well-tolerated after prolonged administration.

Adult↗
PubMed1997

Moderate beer consumption and positive biochemical changes in patients with coronary atherosclerosis.

OBJECTIVES: The aim of this study was to evaluate the influence of moderate beer consumption on lipid metabolism and antioxidant activity in patients (pts) with coronary artery disease (CAD). SUBJECTS: Forty-eight male pts with CAD not alcohol beverages consumers were randomly divided into experimental (EG) and control (CG) groups, 24 pts each. SETTING: Rehovot University Hospital, Israel. INTERVENTION: Every patient of the EG during a period of 30 consecutive days consumed 330 ml of Maccabee beer (> 20 g of alcohol). The pts of the CG did not consume alcohol during the trial period. METHODS: A wide range of tests including total cholesterol, LDL-C, HDL-C, total tocopherol and alpha-tocopherol. RESULTS: Only in the pts of the EG were found a tendency to an increase of the level of HDL-C and a statistically significant rise in the level of total tocopherol (P < 0.025) and alpha-tocopherol (P < 0.025). CONCLUSIONS: Even a short period of moderate beer consumption leads to some favourable biochemical changes in blood of pts with CAD which are widely regarded as indicators of CAD prevention.

Alcohol Drinking↗
PubMed1997

Childhood sexual abuse among homosexual men. Prevalence and association with unsafe sex.

Of 327 homosexual and bisexual men participating in an ongoing cohort study pertaining to risk factors for HIV infection who completed a survey regarding history of sexual abuse, 116 (35.5%) reported being sexually abused as children. Those abused were more likely to have more lifetime male partners, to report more childhood stress, to have lied in the past in order to have sex, and to have had unprotected receptive anal intercourse in the past 6 months (odds ratio 2.13; 95% confidence interval 1.15-3.95). Sexual abuse remained a significant predictor of unprotected receptive anal intercourse in a logistic model adjusting for potential confounding variables.

Adolescent↗
PubMed1997

Computer simulation of neuronal toxicity in the spinal cord.

The use of computers to model biological systems is a relatively new research tool. For example, it is possible to write mathematical systems to model neuronal activity involved in memory and learning and to model blood flow in any organ such as the brain. There is also an interest in designing computer-controlled machines to simulate human activities such as hand movements and vision. One of the most important uses of computer modeling is as a research tool to test hypotheses and aid in formulating new hypotheses. This enables the investigator to apply preliminary tests on several experimental strategies and select for animal experimentation the ones that are most likely to produce unambiguous and interpretable results. In the following article, we describe a computer model of neuron toxicity in the mammalian spinal cord.

Dynorphins↗
PubMed1997

Assessing the clinical need for short-term conversion from oral to parenteral angiotensin converting enzyme inhibitor therapy in hypertensive patients. A quinapril to quinaprilat placebo-controlled model.

UNLABELLED: RATIONALE AND STUDY DESIGN: This study assesses safety and efficacy when hypertensive patients convert from an oral angiotensin converting enzyme inhibitor, quinapril, to its intravenous counterpart, quinaprilat, and evaluates the need for short-term conversion from oral to parenteral therapy. Blood pressure was measured by clinical measurements using a sphygmomanometer and by 24-h ambulatory blood pressure monitoring. During a placebo-baseline phase, patients blood pressure had to increase within 3 days in the absence of an angiotensin converting enzyme inhibitor. Responding patients were stabilized on oral quinapril and then randomized to 3 days of double-blind treatment with one 5 ml or 10 ml injection twice daily of quinaprilat or placebo. RESULTS: Overall response to quinaprilat in ambulatory blood pressure monitoring and clinic blood pressure measurements was not statistically or clinically different from the response to oral quinapril therapy during baseline. Withdrawal from quinapril resulted in clinically significant increases in all blood pressure measurements compared with baseline therapy; the differences between placebo and quinaprilat therapy were statistically and clinically significant. Two patients treated with quinaprilat withdrew due to hypotension; one patient required a dosage reduction. Parenteral quinaprilat safely maintained blood pressure control whereas placebo control did not during the 72-h interruption of quinapril.

Administration, Oral↗
PubMed1996

Intentional injury surveillance in a primary care pediatric setting.

OBJECTIVE: To describe intentional injuries identified by primary care providers caring for children and adolescents, as reported through a prospective surveillance system. SETTING: Pediatric departments at four sites affiliated with a large health maintenance organization in eastern Massachusetts. DESIGN: Primary care providers completed brief injury encounter reports for patients aged 3 to 18 years treated for an intentional injury during a 20-month study period. For comparison purposes, a convenience sample of medical record was reviewed. RESULTS: Two hundred eleven injury encounter reports were received, representing a reported rate of 4.1 intentional injuries per 1000 panel members per year. These injuries ranged from contusions and lacerations to sexual assault and homicide. The median age of children at the time of injury was 14 years (interquartile range, 12 to 16 years), older than the population median age of 10 years (interquartile range, 6 to 14 years) (P<.001, Wilcoxon Signed Rank Test). Boys had a relative risk 1.5 times that of girls (P<.05, binomial test). Almost half of the injuries to adolescent girls resulted from encounters with other girls; 10% were the result of dating violence. In most cases, the patient and his or her assailant were friends or acquaintances (56%). This prospective surveillance detected, at most, 67% of intentional injuries seen, while medical record review detected 59% of the total identified injuries. CONCLUSIONS: Primary care pediatricians can identify and treat children and adolescents for intentional injuries. As these patients may form an appropriate group for interventions directed at reducing the risk of future intentional injuries, more effective public health surveillance must be developed.

Adolescent↗
PubMed1996

Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis.

OBJECTIVE: To determine the frequency, clinical associations, and any major histocompatibility complex correlations of antifibrillarin antibodies in patients with systemic sclerosis (SSc). METHODS: Antifibrillarin antibodies were determined by indirect immunofluorescence, immunoblotting, and immunoprecipitation, and HLA class II alleles by DNA oligotyping, in a large cohort of SSc patients. RESULTS: Antifibrillarin was found in 8% of 335 SSc sera and was significantly more common in blacks (16%) than whites (5%), in males (33%) than females (14%), and in patients with cardiac, renal, or gut involvement. The HLA class II haplotype DRB1*1302, DQB1*0604 was found significantly more frequently in SSc patients with antifibrillarin compared with race-matched normal controls and 260 SSc patients without antifibrillarin. In addition, 1 or more of the HLA-DQB1 alleles *0604, *0301, *0602, and/or *0302 was found in all antifibrillarin-positive patients, and 62% of the antifibrillarin-positive patients had 2 of these HLA-DQB1 alleles, a highly significant difference from both race-matched normal controls and antifibrillarin-negative SSc patients. CONCLUSION: Antifibrillarin, although an infrequent nucleolar autoantibody, is a marker for severe SSc, especially in blacks and males, and is strongly associated with a unique HLA haplotype, as well as with combinations of certain HLA-DQB1 alleles.

Alleles↗
PubMed1996

The centromere kinesin-like protein, CENP-E. An autoantigen in systemic sclerosis.

OBJECTIVE: Autoantibodies directed against centromere proteins (CENPs) are a serologic feature in some patients with systemic sclerosis (SSc). Previous studies have focused on autoantibodies to CENPs A, B, and C. CENP-E is a recently described 312-kd protein that also localizes to the centromere. Therefore, we studied the presence of autoantibodies to recombinant CENP-E in patients with SSc. METHODS: Sixty sera from patients with the SSc spectrum of diseases were screened for the presence of autoantibodies against CENP-E, by indirect immunofluorescence and immunoblotting using recombinant CENP-E protein. HLA class II alleles were determined by DNA oligotyping. RESULTS: Among the SSc sera, 15 of 60 (25%) demonstrated antibody reactivity with recombinant CENP-E, and 14 of these 15 sera (93%) had antibodies directed against another CENP. Anti-CENP-E was seen in 13 of 30 sera with anti-CENP (43%). All patients with anti-CENP-E had a limited form of SSc, known as the CREST variant (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). When patients with anti-CENPs A, B, or C were compared with patients with anti-CENP-E, no unique clinical features in the anti-CENP-E positive group were identified. Ninety-three percent of the patients with anti-CENP-E had HLA-DQB1 alleles that had polar amino acids at position 26 (primarily DQB1*05), similar to patients with other CENP autoantibodies. CONCLUSION: Antibodies to CENP-E are common in patients with SSc, and are seen in higher frequency in sera from patients with a limited form, or CREST variant, of the disease.

Autoantibodies↗
PubMed1996

Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis.

OBJECTIVE: To examine interrelationships among myositis subsets, autoantibodies, and major histocompatibility complex (MHC) class II alleles across ethnic lines, and to localize genetic susceptibility (presence of HLA-DR versus DQ) to myositis within the MHC class II region. METHODS: MHC class II alleles (HLA-DRB1, DQA1, and DQB1, detected by DNA oligotyping) and myositis-specific autoantibodies (MSA) were determined in 224 patients with various myositis syndromes, including 89 whites, 89 African-Americans, 25 Mexican-Americans, and 21 Japanese. RESULTS: Anti-Jo-1 (histidyl-transfer RNA [tRNA] synthetase) and other MSAs (anti-PL-12, anti-PL-7, anti-OJ, anti-EJ, anti-KJ, anti-tRNA, and anti-signal recognition particle) were equally distributed among the races, but occurred more often in patients with polymyositis (PM) than in those with dermatomyositis (DM) or other myositis syndromes. MSA frequencies were significantly positively associated with anti-Ro (SS-A) (P = 0.002), and significantly negatively associated with anti-U1 RNP (P = 0.003). Frequencies of the HLA-DRB1*0301 (DR3), DQA1*0501, and DQB1*0201 (DQ2) alleles (and haplotype) were each increased in white patients with myositis, especially those with PM, but most strikingly in those with MSAs. However, in the other ethnic groups, except the Japanese group, only frequencies of HLA-DQA1*0501 and the structurally similar DQA1*0401 alleles were significantly increased. The presence of HLA-DQA1*0501 or *0401 was most significantly associated with anti-Jo-1, anti-PL-12, and other MSAs, compared with myositis patients without MSAs (P = 0.0008, Pcorr = 0.01, odds ratio [OR] = 3.7), and with normal, ethnically matched controls (P = 3 x 10(-7), Pcorr = 1 x 10(-6), OR = 6.5). Among MSA-positive patients who were negative for HLA-DQA1*0501 and *0401, including Japanese patients, the HLA-DQA1*0102 and *0103 alleles predominated. In addition, there appeared to be a negative association of the HLA-DR2 alleles (DRB1*1501 and *1503) with PM (P = 0.007, Pcorr not significant, OR = 0.39), but not with DM or myositis overall. CONCLUSION: By transracial gene mapping, genetic susceptibility to anti-Jo-1 and other MSAs in patients with myositis can be localized within the MHC region to the HLA-DQA1 locus.

Adult↗
PubMed1996

The impact of the Medicare Influenza Demonstration Project on influenza vaccination in a county in Massachusetts, 1988-1992.

Influenza and related pneumonia continue to cause significant amounts of morbidity and mortality despite the availability of effective vaccines. Two comparable counties in Massachusetts served as project areas of a national trial to see if reimbursement for immunizing Medicare-B eligible recipients against influenza would increase the use of the vaccine and reduce the costs attributed to related morbidity. Providers of health and social services to elders were recruited to participate in one county. A variety of professional and public education campaigns and media were used to promote influenza immunizations. Laboratory-based surveillance was instituted in both counties to assess the extent of circulating virus in each. Vaccine was made available to medical providers in both counties. While the amount of vaccine used in the comparison county increased by 6% from pre-project time (16,000 to 17,000 doses administered), vaccine use increased 219% in the intervention county (21,250 to 46,494 doses administered). In a post-project survey of participating physicians, 88% of 238 respondents reported administering less than 100 doses of influenza vaccine per year prior to the project. By the end of the project, only 32% administered less than 100 in the previous year. This project demonstrated the need for educating both the provider and the public in order to successfully promote immunizations. It was not clear, however, if reimbursement was a more important factor for promoting influenza immunizations than was universal distribution of free vaccine.

Aged↗
PubMed1996

Data on apheresis, blood collection, and transfusion-related activities: statistical analyses of the American Association of Blood Banks institutional membership questionnaires.

BACKGROUND: The American Association of Blood Banks annually surveys institutional members on activities pertinent to blood collections, apheresis, and transfusions. STUDY DESIGN AND METHODS: Retrospective descriptive statistics and comparative statistical analyses including trend tests were performed on selected topics from the 1989, 1990, and 1991 Institutional Questionnaires. The data were compiled by institution type, namely, regional and community blood donor collection centers and hospital-based facilities. Evaluated topics included the apheresis and therapeutic procedures performed, transfusion-associated AIDS and hepatitis, and the blood components (red cells, platelets, fresh-frozen plasma, and cryoprecipitate) that were collected, transfused, or outdated or discarded. RESULTS: Significant findings (p<0.05) included upward trends over time in the numbers of donor plateletpheresis units collected and transfused and in the numbers of random-donor platelet concentrates collected by hospitals. There was an upward trend over time in the outdating or discarding of all blood component types that was reported by hospitals. Data from blood centers showed the outdating or discarding of significant numbers of apheresis platelets, fresh-frozen plasma, and cryoprecipitate. No significant trends were identified in the reported cases of transfusion-associated hepatitis or AIDS. CONCLUSION: Ongoing data analysis of the institutional questionnaires provides information on trends in blood collection and transfusion-related activities.

Blood Banks↗
PubMed1996

Preoperative clinical, EEG, and imaging findings do not predict seizure outcome following temporal lobectomy in childhood.

Although certain clinical, electroencephalographic (EEG), magnetic resonance imaging (MRI), and pathologic findings in adults with intractable temporal lobe epilepsy predict seizure outcome following temporal lobectomy, predictors of seizure outcome have not been studied systematically in pediatric temporal lobectomy series. We retrospectively analyzed preoperative clinical, EEG, and neuroimaging findings with reference to seizure outcome (seizure free or non-seizure free) in 33 children (mean age, 9.3 years) who underwent tailored temporal lobe resections for intractable temporal lobe epilepsy. Trends were apparent with (1) younger age at seizure onset, younger age at surgery, shorter duration of epilepsy, localized unilateral temporal lesions on MRI, and right-sided surgery more frequently associated with a seizure-free outcome, and (2) significant prior history, daily preoperative seizures, generalized motor seizures, mental retardation, and localized unilateral temporal epileptiform EEG activity more frequently associated with a non-seizure-free outcome. However, none of these findings, alone or in combination, correlated with postoperative seizure status at a statistically significant level. Submitting the four variables generally considered to be most predictive of favorable outcome (ie, normal intelligence, unilateral ictal and interictal EEG discharges, and focal temporal MRI lesion) to a multiple-cutoff procedure did not predict seizure freedom. Our data indicate that predictors of outcome of temporal lobectomy in adults may not apply in children, perhaps due to inherent neurobiologic differences in the etiology and expression of temporal lobe epilepsy, and should therefore not be used as sole determinants of surgical candidacy in children.

Adolescent↗
PubMed1996

MHC studies of the primary antiphospholipid antibody syndrome and of antiphospholipid antibodies in systemic lupus erythematosus.

OBJECTIVE: To study the association of HLA Class I, II, and III alleles with antiphospholipid antibodies, both in patients with systemic lupus erythematosus (SLE) and patients with primary antiphospholipid antibody syndrome (APS). METHODS: We studied Caucasian patients with SLE (n = 91) and with primary APS (n = 16) followed at the Ottawa General Hospital Rheumatic Disease Unit. Antiphospholipid antibodies (aPL) were defined by a positive IgG anticardiolipin antibody by serum ELISA and/or the presence of a lupus anticoagulant. HLA Class I by serology and Class II by restriction fragment length polymorphism were compared in patients with and without serum aPL, and in patients with primary APS compared to controls. C4A null alleles were studied in patients with primary APS. RESULTS: aPL were found in 19 of 91 (21%) patients with SLE, and were associated with deep venous thrombosis in this group. In patients with primary APS, stroke, deep vein thrombosis, and recurrent fetal loss were the most common clinical features. HLA-DR17(3) and Dw24 were decreased in patients with SLE with aPL and in patients with primary APS. HLA-DR4 and the linked DR53 were significantly increased in patients with primary APS compared to patients with SLE. In patients with aPL (SLE and primary APS) compared to patients with SLE without aPL, associations were found with HLA-DR53 (p = 1.5 x 10(-4), RR 5.1), DR7 (p = 0.01, RR 5.6), and to a slightly lesser degree DQ7 (p = 0.005, RR 3.6). C4A null alleles by protein allotyping and the C4A gene deletion were not associated with primary APS. CONCLUSION: We confirm the association of aPL with HLA Class II alleles. The strongest association with aPL in our study is with the HLA-DR53 haplotypes, some of which include the DQ7 allele, as suggested in an earlier study. The HLA-B8, DR17, DQ2 haplotype so closely associated with SLE is significantly decreased in both patients with aPL and with primary APS. C4A null alleles are not associated with primary APS in this population. Our study suggests the aPL response in SLE and primary APS is immunogenetically distinct from SLE itself.

Alleles↗
PubMed1996

Evaluation of enalapril/diltiazem ER in hypertensive patients with coexisting renal dysfunction. Enalapril/Diltiazem ER in Hypertensive Renal Disease Group.

Both enalapril and long-acting diltiazem have been shown to effectively lower blood pressure (BP) in hypertensive patients. Furthermore, in clinical studies, these two agents provided beneficial renal effects in these patients when administered on a long-term basis. A combination of enalapril/diltiazem ER was evaluated in 62 patients with Stage 1-3 hypertension and coexisting renal disease. This trial used a multicenter, randomized, double-blind, parallel group design. The study consisted of a 12-week double-blind phase followed by a 6-month open-label extension phase. The combination of enalapril/diltiazem ER was shown to reduce BP following both short-term and long-term treatment phases. Patients in Renal Group I (creatinine clearance CrCl): 30-59 ml/min/1.73 m2) had decreases of -18/-16 and -25/-20 mm Hg after 12 weeks and 9 months of therapy, respectively. Those in Renal Group II (CrCl: 10-29 ml/min/1.73 m2) had similar decreases of -23/-18 and -23/-19 mm Hg at these time points. The adverse events, in both phases, were those associated with the respective monotherapies. A reduction in CrCl with a coincident decrease in proteinuria was noted for both renal groups. The combination of enalapril/diltiazem ER lowered BP and was generally well tolerated by the patients. The combination of these two agents should improve the management of hypertensive patients.

Adult↗
PubMed1996

Chemosensitization of human hepatocellular carcinoma cells with cyclosporin A in post-liver transplant patient plasma.

We previously showed that combined neoadjuvant doxorubicin (DOX) treatment and orthotopic liver transplantation produced a 3-year tumor-free survival rate of 54% in stage II-IVa nonresectable hepatocellular carcinomas (HCCs). These patients received posttransplant immunosuppressive doses of cyclosporin A (CsA). CsA has been shown to modify the function of a membrane P-glycoprotein (Pgp) whose overexpression is associated with a multidrug-resistant (MDR1) phenotype. This study utilized HCC cell lines to characterize the in vitro chemomodulatory properties of CsA as found in posttransplant patient plasma to consider the hypothesis that CsA may prolong posttransplant survival by enhancing the therapeutic efficacy of DOX against multidrug-resistant hepatoma cells. We characterized Pgp expression in the HCC lines Hep3B, Hep G2, and SK-HEP-1 by immunohistochemistry and the reverse transcription-polymerase chain reaction. The combined cytotoxicity of DOX + CsA was examined by [3H]thymidine uptake and flow cytometric drug-retention assays. Pgp expression was assessed further after prolonged (10-day) treatment with CsA. Hep3B and Hep G2 cells expressed low to moderate levels of Pgp. The effective DOX dose required for inhibiting MDR1(+) Hep3B and Hep G2 cell proliferation by 50% (DOX IC50) was 44.5 ng/ml and 43.5 microgram/ml, as compared with 10.7 ng/ml for Pgp-negative SK-HEP-1 cells. Optimal concentrations of CsA (0.8 micrometer) lowered DOX IC50 for Hep3B cells and Hep G2 cells by 6-fold and 4-fold, respectively. Similarly, plasma from patients containing immunosuppressive levels of CsA lowered DOX IC50 of the MDR1(+) Hep G2 cells by up to 4-fold. Prolonged exposure to CsA did not affect its chemosensitizing capacity or Pgp expression of HCC cells. PSC-833, a nonimmunosuppressive analogue of CsA, was equally effective in reducing the DOX IC50 of MDR1(+) HCC cells. CsA and PSC-833 increased drug retention by approximately 75%, but did not significantly affect hepatoma cell viability or Pgp expression. Pharmacological concentrations of cyclosporin analogues, including one nonimmunosuppressive form, enhance DOX cytotoxicity of MDR1(+) HCC cells by modulating drug retention. CsA as found in posttransplant patient plasma enhanced DOX cytotoxicity to human MDR1(+) hepatoma cells in vitro, albeit at less than optimal chemosensitizing concentrations. Prolonged exposure to CsA did not affect its chemosensitizing properties or block Pgp expression of HCC cells. These findings support our hypothesis that in vivo immunosuppressive levels of CsA may enhance DOX chemotherapeutic efficacy on MDR1(+) HCC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗