YETTI HERNANINGSIH, 091170109 (2016) EKSPRESI SURVIVIN DAN HEAT SHOCK PROTEIN (HSP)27 AKIBAT PAPARAN VINKRISTIN PADA ANAK LEUKEMIA LIMFOBLASTIK AKUT (LLA) DENGAN LUARAN KEMOTERAPI FASE INDUKSI YANG BERBEDA SERTA PENGARUHNYA PADA SIKLUS DAN APOPTOSIS SEL. Disertasi thesis, Universitas Airlangga.

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Abstract

Background: Pediatric ALL patients show different chemotherapy outcome, although improvement has been made in risk classification or chosen chemotherapy drug, but nonremission outcome is still beyond among Asian countries, and the mechanism has not been discovered yet. Objective: To investigate the mechanism of nonremission in pediatric ALL patients. Patients and Methods: Patients were recruited from the Hematology Oncology Division of Pediatric Department Soetomo Hospital Surabaya aged 1-14 years old. Research was performed in 2 types, ex vivo and in vivo study. Samples for ex vivo study consisted of 8 remission and 6 nonremission patients. Samples for in vivo study consisted of 10 samples pre and post chemotherapy, and 25 samples who had been followed for outcome or early death. Parameter examinations were survivin, hsp27, apoptotic cell, also S and G2/M phase cell cycle. All specimens were BMMC and all parameters run on flowcytometry Facs Calibur. Each specimen of ex vivo study underwent 2 cultures, in RPMI 20% FBS with and without vinristine, while the samples of in vivo study obtained protocol chemotherapy based on risk criteria. Results: Ex vivo study compared each parameter from culture between remission and nonremission group, also between group with and without vincristine. The results were then analyzed for causality between vincristine, survivin, hsp27, apoptosis, S and G2/M phase cell cycle. Independent t test, Mann Whitney, categorical regression, logistic regression and descriptive analysis were used in this study. The results of ex vivo study showed no significant difference in survivin and hsp27 expression between remission and nonremission group, also group with and without vincristine. Vincristine induce survivin only in nonremission group, not in remission group. For in vivo study, survivin and hsp27 post chemotherapy prone to decrease when compared with pre chemotherapy in remission group. Survivin and hsp27 had no significant difference and correlation between remission outcome and early death group. Conclusions: Survivin contributes nonremission outcome mechanism of vincristine exposure, but not for hsp27.

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