Search
- Page Path
-
HOME
> Search
Original Articles
-
Expressions of Multidrug Resistance-Related Genes in Gastric Cancer Tissue and Normal Gastric Mucosal Tissue
-
Seok Hun Song, Sang Woon Kim, Sun Kyo Song, Joon Hyuk Choi, Jeoung Hee Ha, Kyung Hee Lee
-
Cancer Res Treat. 2001;33(4):302-308. Published online August 31, 2001
-
DOI: https://doi.org/10.4143/crt.2001.33.4.302
-
-
Abstract
PDF
- PURPOSE
This study was conducted to evaluate the expressions of the mdr1 gene and the MRP gene in tumor and adjacent normal gastric tissues.
MATERIALS AND METHODS
The specimens were obtained from 53 patients who had gastric cancer. None of these patients had received any kind of preoperative chemotherapy. The reverse transcription polymerase chain reaction and immunohistochemical stain were used to check the level of expressions of mRNAs and their associated proteins.
RESULTS
Highly positive expressions of mdr1 mRNA, MRP mRNA, p-glycoprotein, and MRP (multidrug resistance associated protein) were observed in the tumor and the adjacent normal tissues. Most tumor tissues coexpressed mdr1 mRNA and MRP mRNA significantly (p<0.001). The expression of these genes in the tumor was much stronger than in the normal counterpart tissues. The expression of the p-glycoprotein was correlated only with the pathological stage (p<0.05). MRP expression was correlated with lymph node metastasis (p<0.05).
CONCLUSION
Normal gastric tissue showed strong physiologic expressions of the mdr1 and MRP genes. Overexpressions of these genes were observed in gastric cancer tissue. The presence of multidrug resistance should be considered when planning anticancer chemotherapy for treating gastric cancer.
-
Clinicopathologic Significance of Multidrug Resistance Protein Expression in Patients with Stage III Gastric Adendegrees Carcinoma
-
Sae Hyun Kim, Wan Ku Lee, Hyun Kim, Young Nam Kim, Seung Min Park, Su Jin Choi, Hyo Suk Park, Myung Jin Joo, Kwang Min Lee, Jong Myung Lee, Sung Hye Shin, Min Chul Kim
-
J Korean Cancer Assoc. 2000;32(3):487-496.
-
-
-
Abstract
PDF
- PURPOSE
We wanted to determine the prognostic significance of P-glycoprotein (Pgp) and multi drug resistance-assdegrees Ciated protein (MRP) in stage III gastric adendegrees Carcinoma by evaluating whe ther the Pgp and/or MRP expression correlate with various clinicopathological parameters and survival rates.
MATERIAL AND METHODS: The expression of Pgp and/or MRP were studied immunohistdegrees Chemi cally by ABC method with paraffin-embedded tissue specimens which were surgically obtained from 64 cases of stage III gastric adendegrees Carcinomas at the Department of Surgery, Presbyterian Medical Center from 1991 to 1992. Statistical differences of both expression in various factors including survival rates and clinicopatholgical parameters were sought.
RESULTS
Expression rates of Pgp and MRP group were 50.0% and 43.7% respectively. There was no significant correlation between expression of two proteins and various clinicopathological variables such as age, sex, stage, tumor depth, number of metastatic node, tumor size, site and method of operation. However, in case of the degree of differenciation, the expression of Pgp and/or MRP was significantly greater in well differenciated adendegrees Carcinoma than in poorly dif ferenciated adendegrees Carcinoma (p=0.001, p=0.012).
Statistically, no significant correlations between the expression of Pgp and/or MRP and overall survival rates were found.
CONCLUSION
These results suggest that the Pgp and/or MRP expression in patients with stage III gastric adendegrees Carcinomas are not useful in determining postoperative chemotherapy and as an independent predictor of survival.
-
A Phase 2 Trial of Verapamil for Reversal of Drug Resistance in Refractory Non - Hodgkin's Lymphoma
-
Keun Chil Park, Baek Yeol Ryoo, Young Hyuk Im, Sung Wook Kang, Jhin Oh Lee, Taik Koo Yun, Ho Sang Shin
-
J Korean Cancer Assoc. 1999;31(2):313-319.
-
-
-
Abstract
PDF
- PURPOSE
Drug resistance is one of the major obstacles to treatment of cancer. Multidrug resistance (MDR) caused by overexpression of p-glycoprotein (Pgp) in cancer cell membrane is a well-known mechanism of drug resistance in in vitro system and was reported to be a significant mechanism of resistance in non-Hodgkins lymphoma (NHL). Verapamil, a calcium channel blocker, is proven in vitro to overcome the MDR caused by Pgp. We performed a phase II trial of verapamil in patients with NHL refractory to EPOCH regimen (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) to overcome the MDR caused by Pgp.
MATERIALS AND METHODS
Verapamil was administered via intravenous route from 1 hour before to 12 hour after the 96-hour infusion of etoposide, doxorubicin, and vincristine which were known to be substrates of Pgp in EPOCH regimen.
The dose of verapamil was 0.15 mg/Kg in bolus and 0.2 mg/Kg/hr in infusion at the beginning and escalated by 0.05 mg/Kg/hr every 24 hours if there was no dose-limiting toxicities such as 2nd or 3rd degree AV block, hypotension, or congestive heart failure. Plasma verapamil concentrations were measured every 24 hour by gas chromatography. Mdrl expression level in tumor tissues was measured by RT-PCR.
RESULTS
From Feb. to Nov. 1994, 14 patients were treated with this protocoL However, poor tolerability and no response in these patients led to early closure of the study at this 1st stage of patient accrual according to Gehans method. Among 14 patients, 12 experienced 2nd or 3rd degree AV block and/or hypotension and required temporary cessation of infusion and reduction of verapamil dose. However, there was no congestive heart failure or treatment-related death.
The peak concentrations of verapamil were 0.29-1.94 pM (mean 0.93 pM) and mean concentrations during the 4-day infusion were 0.22-1.21 pM (mean 0.6 pM). Mdrl expression levels measured in 6 patients were 0.99-14.43 U (median 4.39).
CONCLUSION
These results suggest that verapamil in this dose and schedule was neither tolerable nor effective for the reversal of drug resistance in NHL patients.
-
Expression of DNA Topoisomerase II and P-Glycoprotein in Breast Cancer
-
Hye Rim Park, Eun Ha Jung, Jin Hee Sohn, Young Euy Park
-
J Korean Cancer Assoc. 1997;29(2):243-249.
-
-
-
Abstract
PDF
- PURPOSE
To determine whether the expression of DNA topoisomerase II and P-glycoprotein are of prognostic value.
MATERIALS AND METHODS: We evaluated the expression of DNA topoisomerase II and P-glycoprotein immunohistochemically in a retrospective study of samples from 44 patients with breast cancer. Thirty two among 44 patients (72.7%) received chemotherapeutic treatments (CMF or FAC protocol) and/or tamoxifen postoperatively.
RESULTS
P-glycoprotein was detected in the 27 samples of 44 patients (61.3%). The expression of P-glycoprotein was increased in the patients older than 50 years, with distant metastases, and with death on follow-up. DNA topoisomerase II was detected in the 34 samples of 44 patients (77.2%).
The expression of topoisomerase II was increased in the patients younger than 50 years, with recurrent tumor, with distant metastases, and with death on follow-up. The expression of P-glycoprotein and topoisomerase II was not correlated with other clinico-pathological factors including the size of primary tumor, involvement of lymph node, histologic grade, and clinical stage. The correlation between expression of P-glycoprotein and topoisomerase II was not significant.
CONCLUSION
The immunohistochemical evaluation of P-glycoprotein and topoisomerase II before treatment in breast cancer has little clinical prognostic value.
-
Expression of Multidrug Resistance P-Glycoprotein in Breast Carcinoma
-
Sung Sik Kang, Se Heon Cho, Sang Soon Kim, Jin Sook Jung, Sook Hee Hong
-
J Korean Cancer Assoc. 1994;26(6):912-926.
-
-
-
Abstract
PDF
- In 38 women with breast carcinoma who had locally advanced cancer without distant metastasis, the expression of P-glycoprotein was evaluated, using JSB-1 monoclonal antibody by ABC-immunoperoxidase method, P-glycoprotein was detected in 35 of 38 tumor samples(91.4%). Result were expressed in a semiguantitative manner, taking into account the number of posi- tive tumor cells(N index) and the specific staining index(I index). The frequencies of higher expression(N+I+2 or I+3) were detected in 0% of grade I, 33% of grade II and 90.9% of grade III in infiltrating duct carcinoma. Recurred cases were 4 out of 38(10.5%), of which 3 cases showed high histologic grade and more advanced stage with strong P-glycoprotein expression (N+I+3). Strong P-glycoprotein-positive staining in a majority of tumor cells(N-/I+3) was significantly correlated with histoiogic group with poor prognosis hi#gh histologic grade and recurrence. Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer. The possiblity that Mdrl enhances the invasiveness of cancer was suggested.
-
Multidrug Resistance ( MDR 1 ) Gene Expression in Adult Acute Leukemia : Espression of P-glycoprotein and MDR 1 mRNA and its implication on clinical outcome in adult
-
Hyeoung Joon Kim, Ik Joo Chung, Jae Sung Seo, Keyong Sang Choi, Moo Rim Park, Kang Woo Baek, Youl Bae
-
J Korean Cancer Assoc. 1995;27(6):1017-1030.
-
-
-
Abstract
PDF
- Resistance to multiple chemotherapeutic agents is mainly related to the production of P- glycoproteins, a transmembrane drug efflux pump that is encoded by the multidrug resistance(MDR) gene, MDR I. To investigate whether MDR 1 could be involved in clinical resistance to chemotherapy in adult acute leukemias, We have analyzed prospectively 39 samples from 32 patients(27 at presentation, 5 after relapse) with acute leukemia for the evaluation of overexpression of MDR 1 mRNA and P-glycoprotein by using polymerase chain reactions(PCR) and flow cytometric assay, respectively. The induction rate of first complete remission differed between MDR 1 mRNA-positive and negative groups(37% v 84%, respectively; p=0.02). The survival rate(Kaplan-Meier method) in MDR 1 mRNA negative group was significantly higher than that in MDR 1 mRNA positive group(p=0.02). These results suggest that PCR assay of MDR 1 mRNA is a convenient method to detect expression of MDR 1 gene, and it may be a prognostic factor in the treatment of acute leukemia.
-
Effect of Combined Modality Treatment and Clinical Significance of P-Glycoprotein Overexpression in Patients with Osteosarcoma
-
Yong Seok Yun, Jae Kyung Roh, Hyun Cheol Chung, Jae Yong Cho, Kyoo Ho Shin, Soo Bong Han, Beom Seok Kim, Joon Oh Park, Soo Jung Gong, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jin Sik Min, Byung So
-
J Korean Cancer Assoc. 1996;28(6):1104-1117.
-
-
-
Abstract
PDF
- Osteosarcoma is a highly malignant bone tumor and usually encountered in the first three decades of life. The Prognosis of osteasarcoma treated with surgery alone had been poor, with 20% of the patients surviving 5 years. The addition of adjuvant chemotherapy after surgery has siginificantly improved the outcome of osteosarcoma. The new concept of pre-operative chemotherapy has permitted histological assessment of treatment effect and limb salvage procedures. As the role of chemotherapy has been raised, the resistance of tumors to multiple drugs, such as p-glycoprotein overexpression, has become a major problem in the treatment of osteosarcoma. We retrospectively reviewed the clinical records of 53 patients with stage IIB osteosarcoma who were treated at Yonsei Medical Center and Yonsei Cancer Center between March 1, 1986 and June 30, 1996. The purpose of this study was to assess the efficacy and toxicity of cisplatin(IA)-adriamycin(IV) combination pre-operative chemotherapy and the clinical significance of p-glycoprotein status and histologic response as prognostic factors. Among 53 patients, 33 were male and 20 were female with a median age of 21 years(range: 5~61). The tumor locations were as follows: distal femur 24(45.3%), proximal tibia 17(32.1%), humerus 7(13.2%), proximal femur 3(5.4%), fibular 1(1.9%), radius 1(1.9%). Histologic subclassifications were as follows: osteoblastic type 42(78.2%), telangiectatic type 4(7.5%), chondrablastic type 3(5.7%), fibroblastic type 2(3.8%) and undetermined 2(2.8%). The three year overall survival and disease-free survival rates were 66.1% and 61.9% respectively in all patients. Thirty-two patients were treated by pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy and 21 patients were taken only post-operative adjuvant chemotherapy. No significant difference was found between the two groups in probability of survival and recurrence rates. The histological response ta pre-operative chemotherapy was scored by degree of tumor necrosis. Twenty-two patients had a good response [grade IV, 13(40.6%);grade III, 8(25.0%)] and 11 patients had a poor response [grade II, 6(18.8%);grade I, 5(15.6%)]. The histological response was not significantly related to the probability of the survival rate. However, the recurrence rate was higher in the poor-response group(p=0.04). Overexpression of p-glycoprotein was found in tumors from 11 of l8 patients(61.1%) who were given only post-operative adjuvant chemotherapy. No relation was found between the p-glycoprotein expression and survival rate. The degree of tumor necrosis after pre-operative chemotherapy and initial serum alkaline-phosphatase level were considered as prognositic factors. Other clinicopathologic features including age, gender, anatomical site, histological subclassification,operation types,tumor size.p-glycoprotein expression were not associate with patient outcome. Treatment-related side effects were relatively tolerable and reversible by conservative treatment. Pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy in our study did not show improved survival than conventional post-operative chemotherapy with limited follow-up duration. The degree of histologic response after chemotherapy and the initial alkaline phosphatase level were found to be the major predictor for tumor recurrences, while p-glycoprotein overexpression did not alter the clinical outcome. Further studies are warranted to improve the efficacy of adjuvant chemotherapy and to evaluate the significance of multiple resistance gene overexpression in osteosarcoma.
TOP