Biomedical subjects

O Yoshida

Publications and source records attributed to O Yoshida.

At least 19 recordsLinked to original sources

PubMed1996

Urinary calculi as a late complication of the Indiana continent urinary diversion: comparison with the Kock pouch procedure.

PURPOSE: Although urinary calculi have been frequent late complications of the Kock continent urinary diversion, they have not been regarded as significant problems in patients with the Indiana pouch because of the lack of foreign material present. However, stones developed in a significant percentage of our patients with an Indiana pouch. We investigated the characteristics of stone formation in patients with the Indiana pouch and compared them to those with a Kock pouch. MATERIALS AND METHODS: Detailed clinical courses regarding stone formation were reviewed in 72 patients with a Kock pouch and 54 with an Indiana pouch who had a minimum followup of 12 months. RESULTS: Stones developed in 7 of 54 patients (12.9%) with an Indiana pouch compared to 31 of 72 (43.1%) with a Kock pouch. The incidence gradually increased with longer followup but it was lower in the Indiana than in the Kock pouch group (5-year stone-free rate 84% versus 66%, respectively). Although the stones consisted principally of a mixture of struvite, carbonate apatite and ammonium hydrogen urate, variable amounts of calcium oxalate were identified in 50% of the Indiana pouch calculi. CONCLUSIONS: Not only urinary infections but also metabolic factors were considered to be involved in stone formation within the Indiana pouch. However, the substantially higher rate of stone formation in our Kock and Indiana pouch groups than has been reported in the United States suggested that no or infrequent pouch irrigations in our patients were important risk factors for urinary calculi.

Case-Control Studies↗

PubMed1995

Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma.

Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. In this study, we examined whether constitutive activation of the MAPK cascade was associated with the carcinogenesis of human renal cell carcinomas in a series of 25 tumors and in corresponding normal kidneys. Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. The phosphorylation of MEK and of Raf-1, as monitored by a mobility shift in SDS-PAGE, which is reportedly associated with the activation of these kinases, occurred in 9 of 18 cases (50%) and in 6 of 11 cases (55%) respectively. The activation of MAPKs was correlated with MEK activation (P = 0.0045) and with Raf-1 activation (P = 0.067). Furthermore, overexpression of MEK was found in 13 of 25 cases (52%) by Western blot analysis, and this overexpression was associated significantly with MAPK activation (P = 0.034). No mutations were noted in H-,K-, or N-ras genes by PCR direct sequencing in any of the 25 tumor samples. Of the patients studied, 8 of 18 (44%) stage pT2 patients and four of six (67%) stage pT3 patients showed MAPK activation. The single stage pT1 patient did not evidence MAPK activation. Furthermore, one of seven (14%) grade 1 patients, 9 of 13 (69%) grade 2 patients, and two of five (40%) grade 3 patients showed MAPK activation (grade 1 versus grades 2 and 3, P = 0.046). Our results suggest that constitutive activation of MAPKs may be associated with the carcinogenesis of human RCCs.

Amino Acid Sequence↗

PubMed1995

Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum(II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody.

Cytotoxic chemotherapy has shown little antitumor activity against renal cell carcinoma (RCC). It has been demonstrated that RCC cells secrete interleukin 6 (IL-6) and express IL-6 receptors (IL-6Rs). IL-6 inhibits apoptosis and enhances manganese superoxide dismutase expression. Several anticancer chemotherapeutic agents exert their cytotoxic activity in part through the induction of apoptosis and the production of free radicals. Thus, the resistance of RCC cells to the anticancer agents might correlate with IL-6 expression. The present study tested this hypothesis by examining the effect of anti-IL-6 mAb and anti-IL-6R mAb on the sensitivity of human RCC cells to anticancer chemotherapeutic agents. Treatment of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb in combination with cis-diamminedichloroplatinum(II) (CDDP) or mitomycin C overcame their resistance to CDDP or mitomycin C. However, treatment of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb in combination with Adriamycin, vinblastine or 5-fluorouracil did not overcome their resistance to these anticancer agents. Treatment of CDDP-resistant Caki-1 cells (Caki-1/DDP), two other RCC cell lines (ACHN and A704), and three freshly derived RCC cells with CDDP in combination with anti-IL-6 mAb or anti-IL-6R mAb reversed the resistance to CDDP in all these tumors. We then studied the effectiveness of other platinum derivatives. Treatment of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb enhanced their sensitivity to carboplatin, but not to trans-diamminedichloroplatinum(II). Several experiments investigated the mechanism of the antibody-mediated sensitization of RCC cells to CDDP. Incubation of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb did not change the intracellular accumulation of CDDP. The expressions of the multidrug resistant phenotype (gp170) and c-myc oncogene were not affected by the antibody-mediated sensitization. Treatment of Caki-1 cells with the anti-IL-6 mAb or anti-IL-6R mAb down-regulated the expression of glutathione S-transferase pi mRNA. This study demonstrates that treatment of RCC cells with CDDP in combination with anti-IL-6 mAb or anti-IL-6R mAb can overcome their CDDP-resistance and that the down-regulation of glutathione S-transferase pi expression by anti-IL-6 mAb or anti-IL-6R mAb might play a role in the enhanced cytotoxicity obtained.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

PubMed1995

Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells.

Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia.

Amino Acid Sequence↗

PubMed1995

Effect of recombinant human erythropoietin (rHuEPO) on protein, zinc (Zn), nickel (Ni) and manganese (Mn) in patients undergoing chronic haemodialysis.

Serum protein, albumin, Zn, Ni and Mn concentrations were examined in thirty patients undergoing chronic haemodialysis and whose haematocrit levels had been maintained at 30% for two years with rHuEPO. Serum total protein, albumin, Zn, Ni and Mn concentrations significantly increased with time for two years with rHuEPO therapy. All patients showed improvement of appetite and a normal protein balance. Serum Zn, Ni and Mn levels increased with serum total protein. In conclusion, rHuEPO therapy is very effective for the increase of serum protein, albumin, Zn, Ni and Mn levels in patients undergoing chronic haemodialysis.

Adult↗

PubMed1995

Enhanced susceptibility of c-myc antisense oligonucleotide-treated human renal cell carcinoma cells to lysis by peripheral blood lymphocytes.

C-myc oncogene expression has been implicated in the poor prognosis of human renal cell carcinoma (RCC), and these tumor cells are resistant to cytotoxic effector cells. We hypothesized that the resistance of RCC cells to lysis by cytotoxic effector lymphocytes might be regulated by c-myc expression. The present study tested this hypothesis by examining the effect of c-myc antisense oligonucleotide treatment on the susceptibility of RCC to lysis by cytotoxic lymphocytes. The Caki-1 human RCC cell line constitutively expresses c-myc mRNA, and treatment with c-myc antisense oligonucleotide resulted in a significant inhibition of the expression of c-myc mRNA and enhanced susceptibility to lysis by peripheral blood lymphocytes (PBL). The enhanced susceptibility to lysis was observed by PBL derived from both normal donors and patients with RCC. The susceptibility of c-myc antisense oligonucleotide-treated Caki-1 cells to lysis by lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TIL) was also enhanced. Furthermore, enhanced susceptibility was also seen when freshly isolated autologous tumor cells were used as target cells. The mechanism of the enhanced susceptibility of c-myc antisense oligonucleotide-treated Caki-1 cells to lysis was examined. No effect was observed on the expression of major histocompatibility complex (MHC) class I and MHC class II on the tumor cells. However, there was a modest increase in the frequency of effector-target binding. Further, c-myc antisense oligonucleotide-treated Caki-1 cells were more susceptible to lysis by tumor necrosis factor-alpha (TNF-alpha). The findings of this study demonstrate that c-myc antisense oligonucleotide directly affects established RCC cells and freshly isolated RCC cells by rendering them more susceptible to lysis by PBL, LAK cells, NK cells, and T lymphocytes. The enhanced susceptibility may be due in part to the enhanced sensitivity to TNF-alpha and to the augmentation of PBL binding to tumor cells. The possible clinical implications of these findings are discussed.

Adolescent↗

PubMed1995

Effect of urinary intestinal diversion on urinary risk factors for urolithiasis.

We investigated the effect of urinary intestinal diversion on risk factors for calcium urolithiasis, such as calcium, phosphate, magnesium, uric acid, oxalate and citrate, in 3 groups of patients (Kock pouch, Indiana pouch and ileal conduit). Mean urinary volume was not significantly different among the 3 groups. Mean serum creatinine and 24-hour creatinine clearance in the continent reservoir group were better than in the ileal conduit group. Mean urinary excretion of calcium, phosphate and magnesium was significantly greater in the continent reservoir group than in the ileal conduit group. Although calcium excretion had a positive correlation with 24-hour creatinine clearance, calcium excretion per ml. per minute creatinine clearance still showed a significant difference. Increased calcium excretion is considered to reflect metabolic disturbances resulting from reabsorption of urinary solutes through the intestinal segments. Overall, there was no significant difference in the urinary parameters between the Kock and Indiana pouch groups. While mean urinary oxalate and citrate were within the normal range in all 3 groups, more than a third of the patients in each group were hypocitraturic (less than 100 mg. per day). In none of the 3 groups did the levels of urinary calcium, phosphate and magnesium, as well as other urinary risk parameters show any correlation with the duration of diversion. In summary, our study indicated that the continent urinary reservoir causes a long-term increase in urinary excretion of calcium, phosphate and magnesium. These urinary metabolic alterations might promote the formation of calcium urolithiasis as well as infectious stones. The degree of metabolic alterations may be greater with a continent reservoir than with an ileal conduit.

Adult↗

PubMed1995

Allelic frequency of p53 gene codon 72 polymorphism in urologic cancers.

Alterations in the p53 tumor suppressor gene appear to be important in the development of many human tumors. The wild-type p53 gene has a polymorphism at codon 72 that presents the arginine (CGC) or proline (CCC) genotype, which recently has been reported to be associated with genetically determined susceptibility to smoking-related lung cancers. To determine whether this p53 genotype influences individual risk of urologic cancer and/or its progression, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to assay the allelic frequencies of this polymorphism in 85 renal cell carcinoma patients, 151 urothelial cancer patients, 33 testicular cancer patients, 28 prostatic cancer patients and 56 patients without neoplastic disease. The allelic distributions of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) in patients with renal cell carcinoma (29.4%, 55.3%, 15.3%), urothelial cancers (45.7%, 39.7%, 14.6%), testicular cancer (45.4%, 48.5%, 6.1%) or prostate cancer (42.9%, 50.0%, 7.1%) did not differ significantly from those in the normal controls. However, Pro/Pro genotype in renal cell carcinoma and urothelial cancer (smoking-related cancers) was more frequent than that in prostate cancer and testicular cancer (smoking-unrelated cancers) with borderline significance (P = 0.0881). There was no particular correlation between frequency of the three genotypes and grade or stage of each type of tumor. The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.

Adult↗

PubMed1995

Multidrug resistance-associated protein-mediated multidrug resistance modulated by cyclosporin A in a human bladder cancer cell line.

A doxorubicin-resistant subline (5637/DR5.5) from human bladder cancer cells (5637) was induced by stepwise increase in the doxorubicin concentration. 5637/DR5.5 cells were cross-resistant to vinblastine and etoposide but not to mitomycin C and cisplatin. We analyzed the mdr1, MRP (multidrug resistance-associated protein), and DNA topoisomerase II gene expression using the reverse transcription polymerase chain reaction assay (RT-PCR) and investigated possible differences in the accumulation and efflux of radiolabeled daunorubicin. 5637/DR5.5 cells do not express the mdr1 gene, but the expression levels of MRP are markedly higher than in drug-sensitive 5637 cells. The intracellular accumulation of radiolabeled daunorubicin was markedly decreased in the 5637/DR5.5 cells in comparison with the parent cells. This reduced drug accumulation was associated with an enhanced drug efflux, but was reversed when cells were incubated with cyclosporin A. Cyclosporin A at the concentration of 5 microM caused 3.4-fold enhancement of daunorubicin-sensitivity in the 5637/DR5.5 cells. On the other hand, there was no difference in DNA-topoisomerase II activity between the parent and resistant cells. The resistance of the 5637/DR5.5 cells is therefore associated with an enhanced drug efflux mediated by the MRP gene overexpression, as distinct from P-glycoprotein, and is modulated by cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Ectopic ureter opening into the seminal vesicle in an infant: a case report and review of the Japanese literature.

A case is presented of an ectopic ureter opening into the seminal vesicle associated with hypodysplastic kidney in an infant. We reviewed 135 cases (139 ureteral units) of male ectopic ureter from the Japanese literature and, of the 139 ectopic ureters, 109 were single-system ectopic ureters, and 26 ureters were associated with the ureteral duplication. Sixty-three and 73 ureters opened into the urinary tract and seminal tract, respectively. In patients 15 years or older, 65 cases of ectopic ureter opened into the seminal tract and 33 cases opened into the urinary tract, whereas in children under 15 years, the ectopic orifice was located more often in the urinary tract (26 cases) than in the seminal tract (8 cases). Presenting symptoms differed according to the location of the ectopic orifice. Ectopic ureters opening into the urinary tract most often presented with urinary tract infection and abdominal or lumbar pain. On the other hand, voiding and ejaculatory symptoms as well as perineal or genital pain were characteristic in ectopic ureters opening into the seminal tract. Of the 83 associated renal segments that were surgically removed, dysplasia, hypoplasia and aplasia were found in 22, 24, 14 cases, respectively. It was noteworthy that 48 of the 53 single ectopic ureters opening into the seminal vesicle were associated with ipsilateral renal dysgenesis.

Choristoma↗

PubMed1995

A case of metastatic yolk sac tumor of testis in a child.

We report a case of testicular yolk sac tumor in a child aged 3 years and 6 months with multiple bulky metastases to lung and retroperitoneum (stage IIIB2). After three courses of chemotherapy with a PVB regimen (cisplatin, vinblastine and bleomycin), complete and partial responses were obtained for lung and retroperitoneal lymph node metastases, respectively. The patient was followed-up closely. However, on the basis of a re-elevated alpha-fetoprotein (AFP) after 4 months' follow-up, he was treated with three courses of salvage chemotherapy with a modified VAB-6 regimen (cyclophosphamide, etoposide, actinomycin D, bleomycin and cisplatin), followed by retroperitoneal lymph node dissection. Histologically, only necrotic tissue was found. There is no evidence of recurrence 24 months after lymphadenectomy. There is very little information in the literature on the appropriate management of postchemotherapy residual mass in pediatric testicular tumors.

Child, Preschool↗

PubMed1995

Basic research.

Basic research is currently investigating the molecular cascade associated with bladder cancer development. Many new findings are potential leads towards the improvement of the diagnosis and prognosis of this disease. Special care, however, should be taken in the design of protocols for clinical evaluation of the value of these markers. Some initial guidelines have been put forward in this report.

Alleles↗

PubMed1995

Transurethral microwave thermotherapy for benign prostatic hyperplasia: clinical results after a 1-year follow-up.

Since September 1992, 63 patients with symptomatic benign prostatic hyperplasia (BPH) have been treated with transurethral microwave thermotherapy (TUMT) using the Prostatron device. The International Prostate Symptom Score (I-PSS) and quality of life (QOL) score were used to evaluate subjective symptoms. The mean I-PSS (total, irritative and obstructive scores) and QOL scores had decreased by 40, 38, 45 and 40%, respectively, at 12 months (p < 0.0001). While the mean peak flow rate had increased by 72% (p < 0.001). The clinical efficacy at 12 months was 42%, using a modification of the response criteria proposed at the 2nd International Consultation on Benign Prostatic Hyperplasia. There were no significant differences in the baseline and treatment parameters between those who responded favorably to TUMT and those who did not. The total thermal dose delivered to the prostate did not predict clinical response. However, there was a positive correlation between I-PSS or QOL at baseline and % reduction at 3, 6 and 12 months, and a negative correlation between peak flow rate at baseline and % increase at 3 and 6 months. There were no major complications associated with TUMT during the follow-up period. In summary, our 1-year clinical results are compatible with previous reports, suggesting that TUMT is a safe, effective and lasting non-surgical treatment for BPH. However, evaluation of efficacy should be based on uniform criteria to facilitate comparisons of different clinical trials. The most suitable patient profiles for TUMT could not be identified by retrospective analysis.

Aged↗

PubMed1995

Silicon level in rats with chronic renal failure produced by 5/6 nephrectomy.

Serum, erythrocyte and renal tissue silicon levels in normal Wister rats and in rats with chronic renal failure were examined. The relationship between serum, erythrocyte and renal tissue Si levels, and markers of renal function (BUN, serum creatinine), markers of anemia (RBC, Hb, Hct) and markers of bone formation (serum calcium, phosphate) were studied. Serum and erythrocyte Si levels were directly correlated with the markers of renal function and with serum Pi and serum Ca x P, and inversely with the markers of anemia. Renal tissue silicon levels, on the other hand, correlated only with the markers of anemia.

Anemia↗

PubMed1995

[E-cadherin expression and histopathological features in renal cell carcinomas].

E-cadherin, a member of the cadherin family, plays a major role in cell-cell adhesion of normal epithelium. Recent studies have demonstrated that heterogeneous expression, reduction or loss of E-cadherin is involved in invasion and metastasis of cancer cells. In this study, the localization of E-cadherin in the normal human kidney and the relationship between E-cadherin expression and histopathological features in renal cell carcinomas was examined immunohistochemically. Renal cell carcinoma tissues and normal kidney counterparts were obtained from 20 patients. E-cadherin in the normal kidney was detected in the cell-cell border of the distal tubules, collecting duct and Bowman's capsule but not in the proximal tubules. E-cadherin expression was reduced in all the clear cell type renal cell carcinomas with compact or cystic configuration (n = 15), while it was well preserved in all the papillary type (n = 3) and chromophobe cell type (n = 1) renal cell carcinomas. Different expression patterns between primary site and metastasis, i.e., homogeneously weak in primary tumor and heterogeneously positive in metastatis, was observed in a case of clear cell type renal cell carcinoma. Different patterns of expression between clear and non-clear cell type, or between papillary and non-papillary type, together with strong expression in chromophobe type might reflect the origin of each type of renal cell carcinoma. Further studies will clarify whether the change in expression of E-cadherin is associated with the prognosis of renal cell carcinoma.

Adult↗

PubMed1995

[Prognostic factors of prostatic cancer].

In the past ten years, the treatment of prostate cancer has undergone remarkable changes. Furthermore, systematic prostate biopsy under transrectal ultrasonography or the measurement of prostate specific antigen has provided significant improvement in the detection of prostate cancer. Considering the increasing detection of prostate cancer, it is very important to clarify prognostic parameters in order to select the optimal treatment of given patients with localized or advanced prostate cancer. Recent statistical analyses showed that tumor volume, lymph node involvement and Gleason score would be significant prognostic indicators in localized prostate cancer. In advanced cancer, the response to the initial endocrine therapy might be a good prognostic parameter in addition to the histopathological features of primary tumors. In order to determine the factors which predict the prognosis of prostate cancer more accurately, the molecular biological approach is now ongoing, and may provide novel parameters for the decision making in the treatment of prostate cancer.

Humans↗

PubMed1995

Prognostic criteria in patients with prostate cancer: correlation with volume weighted mean nuclear volume.

PURPOSE: Grading of malignancy in prostate cancer is based on qualitative, morphological examination and suffers from poor reproducibility. On the other hand, estimating the volume weighted mean nuclear volume, which was developed by Gunderson and Jensen based on a stereological technique, is a simple method with high reproducibility. Furthermore, it has been reported that mean nuclear volume is remarkably correlated with prognosis of bladder cancer. We compared mean nuclear volume to 2 histological grading methods and clinical stage to determine the prognosis of prostate cancer using a Cox proportional hazards model. MATERIALS AND METHODS: A retrospective, prognostic study of 52 patients with prostate cancer diagnosed by transurethral resection of the prostate or needle punch biopsy between January 1983 and July 1994 was performed. Unbiased estimates of mean nuclear volume were compared to patient age at diagnosis, clinical stage, histological grading according to the World Health Organization (WHO) classification and Gleason score of the prognostic value. RESULTS: Univariate analysis revealed that estimates of mean nuclear volume (p = 0.0011), clinical stage (p = 0.0014) and WHO classification (p = 0.0010) correlated significantly with progression-free survival, and that clinical stage (p = 0.0005) and estimates of mean nuclear volume (p = 0.0049) correlated significantly with disease-specific survival of patients with prostate cancer. However, multivariate analysis revealed that only estimates of mean nuclear volume and clinical stage were the 2 most powerful independent prognosticators in progression-free and disease-specific survival. CONCLUSIONS: Our results indicate that estimates of mean nuclear volume are prognostically superior to morphological grading of malignancy, such as Gleason score and WHO classification, in prostate cancer.

Aged↗

PubMed1995

Cepharanthin, a multidrug resistant modifier, is a substrate for P-glycoprotein.

P-glycoprotein modulators are respected to be multidrug resistance reversing agents in cancer chemotherapy. Some calcium channel blockers, calmodulin inhibitors or immunosuppressive agents have been used in clinical studies, although the dose of these drugs required to test in vitro experimental data might cause potent pharmacological effects which are not desirable in patients. By using LLC-GA5-COL150 cells that express P-glycoprotein specifically on the apical membranes, we examined the transport of anticancer drugs mediated by P-glycoprotein. Cepharanthin, a biscoclaurine alkaloid, potently inhibits the transport of vinblastine and daunorubicin, both commonly used anticancer agents. The 50% inhibitory concentration of cepharanthin on daunorubicin transport was 2.06 microM. Combined inhibitory effects on daunorubicin transport were observed when cepharanthin was used together with cyclosporin A, a potent immunosuppressive agent and P-glycoprotein modulator. Cepharanthin itself was transported by P-glycoprotein. Transcellular transport of cepharanthin across LLC-GA5-COL150 cell monolayers was saturable when its concentration was under 5 microM, and the transport was inhibited by P-glycoprotein modulators. These results indicate that cepharanthin can reverse multidrug resistance, and proper combination with other P-glycoprotein modulators could potentiate its inhibitory effect on expelling the anticancer drugs out of the cell via P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗