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      • Methylation Status and Immunohistochemistry of BRCA1 in Epithelial Ovarian Cancer

        Pradjatmo, Heru,Dasuki, Djaswadi,Anwar, Mohammad,Mubarika, Sofia,Harijadi, Harijadi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

        Background: Cancer initiation and progression are controlled by genetic and epigenetic events. One epigenetic process which is widely known is DNA methylation, a cause of gene silencing. If a gene is silenced the protein which it encodes will not expressed. Objectives: 1. Identify the methylation status of BRCA1 in patients with epithelial ovarian cancer (EOC)and assess BRCA1 protein expression in tumor tissue. 2. Examine whether BRCA1 gene methylation and BRCA1 protein are associated with survival of epithelial ovarian cancer patients. Methods: The study design was a prospective-cohort study, conducted at Sardjito hospital, Yogyakarta, Indonesia. Results: A total of 69 cases were analyzed in this study. The data showed that the methylation status of BRCA1 in EOC was positive in 89.9%, with clear protein expression of BRCA1 in 31.9%. Methylation status and expression of BRCA1 were not prognosticators of EOC patients. Menarche, CA125 level, clinical stage and residual tumor were independent factors for prognosis.

      • Malignancy Risk Scoring of Hydatidiform Moles

        Pradjatmo, Heru,Dasuki, Djaswadi,Dwianingsih, Ery Kus,Triningsih, Ediati Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

        Background: Several risk factors leading to malignant transformation of hydatidiform moles have been described previously. Many studies showed that prophylactic chemotherapy for high risk hydatidiform moles could significantly decrease the incidence of malignancy. Thus, it is essential to discover a breakthrough to determine patients with high risk malignancy so that prophylactic chemotherapy can be started as soon as possible. Objectives: Development of a scoring system of risk factors as a predictor of hydatidiform mole malignant transformation. Materials and Methods: This research is a case control study with hydatidiform mole and choriocarcinoma patients as subjects. Multiple logistic regression was used to analyze the data. Odds ratios (OR), attributable at risk (AR : OR-1) and risk index ($ARx{\beta}$) were calculated for develoipment of a scoring system of malignancy risk. The optimal cut-off point was determined using receiver operating characteristic (ROC) curve. Results: This study analyzed 34 choriocarcinoma cases and 68 benign hydatidiform mole cases. Four factors significantly increased the risk of malignancy, namely age ${\geq}35$ years old (OR:4.41, 95%CI:1.07-16.09, risk index 5); gestational age ${\geq}$ 12weeks (OR:11.7, 95%CI:1.8-72.4, risk index 26); uterine size greater than the gestational age (OR:10.2, 95%CI:2.8-36.6, risk index 21); and histopathological grade II-III (OR:3.4, 95%CI:1.1-10.6, risk index 3). The lowest and the highest scores for the risk factors were zero and 55, respectively. The best cut-off point to decide high risk malignancy patients was ${\geq}31$. Conclusions: Malignant transformation of hydatidiform moles can be predicted using the risk scoring by analyzing the above four parameters. Score ${\geq}31$ implies high risk patients so that prophylactic chemotherapy can be promptly administered for prevention.

      • Association of The IDH1 C.395G>A (R132H) Mutation with Histological Type in Malay Brain Tumors

        Yusoff, Abdul Aziz Mohamed,Zulfakhar, Fatin Najwa,Sul'ain, Mohd Dasuki,Idris, Zamzuri,Abdullah, Jafri Malin Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.12

        Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.

      • Anti-Proliferative Effects of Dendrophthoe pentandra Methanol Extract on BCR/ABL-Positive and Imatinib-Resistant Leukemia Cell Lines

        Zamani, Afiqah,Jusoh, Siti Asmaa Mat,Al-Jamal, Hamid Ali Nagi,Sul'ain, Mohd Dasuki,Johan, Muhammad Farid Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.11

        Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R ($IC50=192{\mu}g/mL$) compared to K562 ($500{\mu}g/mL$) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.

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        Evaluation on composition, antioxidant and toxicity of Melaleuca cajuputi leaves

        Noor Arif Azimi Md,Yusuf Siti Mahirah,Wahab Wan Nor Amilah Wan Abdul,Adam Md Faizul Ismal Che,Sul’ain Mohd Dasuki 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.4

        Melaleuca cajuputi (MC) is an aromatic herb that belongs to Myrtaceae family. MC leaves are widely used as traditional medicine, cooking flavour and freshening agent in cosmetics. In this study, the proximate analysis of MC leaves comprised of moisture (2.74%), ash (7.76 ± 0.04%), crude fat (4.83 ± 0.20%), calorie (4974 Cal/g), dietary fibre (9.49 ± 0.01%), protein (6.42 ± 0.06%) and carbohydrates (78.25 ± 1.02%). Besides that, in BSLA only MCME produced toxicity effect with LC50 value of 427 µg/mL while MCEO, MCAE and MCDE not showed any toxicity effect based on Meyer’s and Clarkson’s classification. Moreover, MCME produced the highest TPC and TFC value followed with MCAE, MCEO and MCDE which indicated highest free radical scavenging activity. Next, GCMS analysis revealed that 19 compounds are found in MCEO that possess antidepressant and anxiolytic effects. Furthermore, the concentrations of heavy metals in MCEO (lead, cadmium, arsenic and mercury) are within normal range concentrations based on British pharmacopoeia 2008.

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