JAK2 mutation and treatment of JAK2 inhibitors in Philadelphia chromosome-negative myeloproliferative neoplasms

ABSTRACTThe Philadelphia chromosome-negative (Ph-negative) myeloproliferative neoplasms (MPNs) polycythaemia vera (PV), essential thombocythaemia (ET) and primary myelofi brosis (PMF) are clonal disorders of multipotent haematopoietic progenitors. The genetic cause of these disorders was not fully defi ned until a somatic activating mutation in the JAK2 non-receptor tyrosine kinase, JAK2V617F, was identifi ed in most patients with PV and a considerable proportion of patients with ET and PMF. The discovery of JAK2 mutation has changed the molecular reclassification of MPNs and served as a genomic target for therapeutic implication. A number of JAK2 inhibitors have been developed and tested for MPNs. Several JAK2 inhibitors have reached the phases of clinical trial and included patients with intermediate-risk or high-risk MF. This population of MF is the best candidate for trials because currently it has no effective therapy besides patients’ poor survival. Considering all clinical data on Ph negative MPNs, JAK2 inhibitors have shown a clinical benefi t and reduced symptoms in the vast majority of MF cases. The most developed among JAK2 inhibitors is Ruxolitinib, which has demonstrated clinical improvement with well tolerated toxicities. However, JAK2 inhibitor was equally active in patients with and without JAK2 mutation. Other JAK2 inhibitors are less developed, but showed a similar clinical benefi t. Furthermore, its effect on the natural course of MPNs in treating patients needs to be investigated.Keywords: myeloproliferative neoplasms – JAK2 mutation – JAK2 inhibitors

Cisplatin Desensitization in a Patient with Nasopharyngeal Carcinoma Experiencing Urticarial Allergic to Cisplatin

Background. Allergic reactions to cisplatin are not uncommon situations with an incidence of 5-20%. In general, allergic reactions to cisplatin is a type 1 hypersensitivity with manifestations of itching, redness, papules, urticaria, chest pain, and anaphylactic symptoms. Desensitization methods are needed for patients who have no alternative medication.Case Report. A 59-year-old woman with nasopharyngeal carcinoma experienced urticaria because of cisplatin in her first cycle of chemotherapy. In the second cycle, chemotherapy desensitization program was applied using a 12-step Castell protocol. We measured vital signs and symptoms every 15 minutes. Administration of cisplatin was completed in 2 hours and the patient tolerated the whole program very well.Discussion. Risk factors of hypersensitivity to cisplatin include age 650 mg, mutation of BRACA1/2 gene, and administration of combined regimens with taxane groups or liposomal inhibitor. Desensitization uses 3 solutions with 12 steps. Solution is 100 times the dilution of the target dose. Solution 2 is 10 times the dilution of the target dose and solution 3 uses the appropriate target dose. Each solution is administered for 15 minutes using an infusion pump. Strict monitoring of vital signs and patient symptoms are done every 15 minutes during the program.Conclusion. Doctors should be aware of allergies to cisplatin. Currently, the allergic reaction to cisplatin can be overcome using the desensitization method when no alternative drug is not available

Association study of LMP-1 expression and promoter methylation status of tumor suppressor gene RASSF1A in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a cancer originating fromnasopharyngeal epithelial tissue. Genetic susceptibility,exposure to carcinogens, and Epstein-Barr virus (EBV) infection are the main factors in NPC development. Latentmembrane protein 1 (LMP-1) is a product of EBV genome, which is able to interact with various intracellular signalingpathways that leads to expression of many proteins, e.g DNA methyltransferase. The increase expression of DNAmethyltransferase could induce hypermetylation of tumor suppressor genes (TSG). Ras-association domain family1A (RASSF1A) is one of TSG that frequently hypermethylated in NPC cases. The aim of this study is to determinethe association between LMP-1 expression and promoter methylation status of RASSF1A in NPC patients. Theresearch subjects were 36 NPC patients of the Dr. Sardjito Hospital, Yogyakarta, Indonesia. Latent membraneprotein 1was stained immunohistochemically using monoclonal antibody OT21C. Ras-association domain family 1Amethylation statuswas examined by methylation specific PCR (MSP) of DNA isolated fromnasopharyngeal brushing.Chi-square analysis was conducted to examine the association between LMP-1 expression and methylation status ofRASSF1A with 95%confidence interval. Latent membrane protein 1 was expressed in 44.4%subjects. The scoresof LMP-1 expression were ranged from 0-8 (average of 1.56±2.16). Ras-association domain family 1A methylatedin 66.7% of subjects. Statistical analysis showed that there was a relationship between LMP-1 expression andmethylation status of RASSF1A (p<0.05). Statistical analysis also showed association between LMP-1 expressionscore and RASSF1A methylation status (p<0.05). It can be concluded that there was an association between theexpression of LMP-1 and RASSF1A methylation status in NPC patients.Keywords: LMP1 - RASSF1A – NPC – hypermethylation - DNA methyltransferase - methylation specific PC

Association study of LMP-1expression and promoter methylation status of tumor suppressor gene RASSF1A in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a cancer originating from nasopharyngeal epithelial tissue. Genetic susceptibility, exposure to carcinogens, and Epstein-Barr virus (EBV) infection are the main factors in NPC development. Latent membrane protein 1 (LMP-1) is a product of EBVgenome, which is able to interact with various intracellular signaling pathways that leads to expression of many proteins, e.g DNA methyltransferase. The increase expression of DNA methyltransferase could induce hypermetylation of tumor suppressor genes (TSG). Ras-association domain family 1A (RASSF1A) is one of TSG that frequently hypermethylated in NPC cases. The aim of this study is to determine the association between LMP-1 expression and promoter methylation status of RASSF1A in NPC patients. The research subjects were 36 NPC patients of the Dr. Sardjito Hospital, Yogyakarta, Indonesia. Latent membrane protein 1 was stained immunohistochemically using monoclonal antibody OT21 C. Ras-association domain family 1A methylation status was examined by methylation specific PCR (MSP) of DNA isolated from nasopharyngeal brushing. Chi-square analysis was conducted to examine the association between LMP-1 expression and methylation status of RASSF1A with 95% confidence interval. Latent membrane protein 1 was expressed in 44.4% subjects. The scores of ~MP-1 expression were ranged from 0-8 (average of 1.56 :t 2.16). Ras-association domain family 1A methylated in 66.7% of subjects. Statistical analysis showed that there was a relationship between LMP-1 expression and methylation status of RASSF1A (

Prognostic Value of Albumin Levels before Therapy on Survival of Nasopharyngeal Carcinoma Patients

Nasopharyngeal cancer (NPC) is a type of cancer in Southeast Asia, with 30-80 cases annually per 10,000 population. Based on the data, about 80% of patients with advanced-stage are diagnosed first, while 20% develop metastases after therapy. A prognostic assessment is essential for the optimization of treatment. Malnutrition is one of the consequences of decreased response to treatment, quality of life, and survival. The patient's albumin determines nutrition. This study was a retrospective study to evaluate the ability of pre-therapy albumin levels to predict long-term mortality in 227 NPC patients at Dr. Sardjito Hospital. Univariate analysis identified albumin as a statistically significant predictive factor for survival (P 0.021). Albumin (ALB) 3.50 was significantly associated with shorter survival. Median Overall Survival showed (OS) ± SE ALB 3.50 vs. ALB 3.50: 9.40 ± 2.56 vs. 17.63 ± 1.51 months, P 0.021, Hazard Ratio (HR) 1.368; 95% CI (1.049–1.783). However, multivariate analysis showed low serum albumin levels before therapy on survival in NPC patients (P 0.778, HR 1.050, 95% CI (0.75–1.469). Treatment was identified as the only independent predictive factor for survival. Albumin before therapy was a potential predictive biomarker to evaluate survival in NPC patients but not an independent predictor

Ketahanan hidup 5 tahun pada pasien kanker payudara

Latar belakang: Berdasarkan data Globocan tahun 2012, insidensi kanker yang tertinggi di Indonesia adalah kanker payudara. Kejadian kanker payudara di Indonesia menduduki peringkat tertinggi diderita oleh perempuan. Masih banyak kematian yang disebabkan oleh kanker payudara. Ketahanan hidup pasien tergantung beberapa faktor yang sangat penting untuk diidentifikasi.Metode: penelitian ini mengunakan rancangan kohort rertrospektif. Sampel pada penelitian ini adalah pasien kanker payudara yang pertama kali terdiagnosa kanker payudara dari 01 Januari 2009 sampai dengan 31 Desember 2009 di RS Sardjito, Yogyakarta. Analisis data menggunakan metode Kapplan Meier dan faktor yang berhubungan dianalisis dengan cox regression.Hasil: Ketahanan hidup 5 tahun pasien kanker payudara adalah 51,07%. Pada analisis bivariat, ada hubungan antara variabel umur diagnosis, pendidikan, stadium klinik , ukuran tumor dan lokasi tumor terhadap ketahanan hidup 5 tahun pasien kanker payudara. Pada analisis multivariat, umur diagnosis memiliki hubungan yang paling kuat (HR=3,73;95%CI=1,0-13,6) terhadap ketahanan hidup (pvalue=0,046).Kesimpulan: Ketahanan hidup pasien kanker payudara pada wanita berusia kurang dari 50 tahun lebih rendah. Wanita muda dengan kanker payudara cenderung memiliki kanker payudara yang lebih agresif pertumbuhannya dan risiko kekambuhan yang besar. Maka diperlukan upaya deteksi dini kanker payudara untuk meningkatkan ketahanan hidup pasien kanker payudara. Analysis of 5-year survival of patients treated for breast cancer at Sardjito Hospital in Yogyakarta province, IndonesiaPurposeThis study aimed to assess the length of life of breast cancer patients as well as factors related to the prognosis of survival of patients.MethodsThis research was a retrospective study. Samples in this study were patients with breast cancer who were first diagnosed with breast cancer from January 1, 2009 until December 31, 2009 at the Dr. Sardjito Hospital, Yogyakarta. The Kaplan Meier method was used for the data analysis, and final factors were reviewed and those that showed significant association were entered in a Cox regression model. Calculations were performed in Stata 12.0.ResultsResults showed the 5 year survival rate was 51.07%. In bivariate analysis, there was a correlation between the age of diagnosis, education, clinical stage, tumor size and tumor location on 5-year survival in patients with breast cancer. For multivariate analysis, age of diagnosis had the most powerful correlation (HR = 3.73; 95% CI = 1.0 to 13.6) on survival (p = 0.046).ConclusionSurvival rates of women with breast cancer aged less than 50 years were lower. Young women with breast cancer tended to have more aggressive breast cancer growth and recurrence risks were greater. Efforts are needed for early detection of breast cancer to improve survival in breast cancer patients

Cox Proportional Hazard Regression Interaction Model and Its Application to Determine The Risk of Death in Breast Cancer Patients after Chemotherapy

Introduction: This research is based on medical record data of breast cancer patients who seek treatment at the Central General Hospital, dr. Sardjito Yogyakarta, from 2018-2021 has as many as 105 patients. Several risk factors for cancer include demographic factors, clinical factors, tumor factors, and therapy. These factors lead to different psychological states of patients, resulting in the rate of recovery and death of patients. Objective: To determine the risk of death in breast cancer patients after chemotherapy. Methods: The method used in this study is Cox Proportional Hazard survival analysis with an interaction model. The variables studied were age, marital status, profession, insurance, BMI, comorbidities, duration of chemotherapy, chemotherapy agent, chemotherapy type, and tumor size. Results: The analysis results using SPSS software obtained the best hazard and survival model with four significant variables, namely the duration of chemotherapy, chemotherapy agents, chemotherapy types, and the interaction between BMI and chemotherapy types. Conclusions: The most significant risk factor for death was palliative chemotherapy type with HR 27.195 and 3-5 chemotherapy agents with HR 4.997. Meanwhile, the long duration of chemotherapy and the interaction between lean BMI and palliative chemotherapy reduced the risk of death by HR 0.967 and 0.128, respectively

Age at diagnosis predicted survival outcome of female patients with breast cancer at a tertiary hospital in Yogyakarta, Indonesia.

INTRODUCTION: Breast cancer is the most common cancer in women in Indonesia. Patients' survival depends on various factors, namely patient-, tumor-, and treatment-related factors. Survival analysis on Indonesian patients has only been reported in a few studies. This study aimed to identify the factors that are associated with five-year overall survival (OS) among patients with breast cancer at a local tertiary hospital in Indonesia. METHODS: A retrospective cohort study was conducted at Dr Sardjito Hospital, Yogyakarta. Female patients diagnosed with breast cancer between January and December 2009 were studied. Socio-demographic and clinicopathological data were collected from the medical and pathological records. The five-year OS rate was assessed using Kaplan Meier method and prognostic factors were analyzed using Cox regression. RESULTS: A total of 213 eligible patients with breast cancer were recruited. The five-year OS probability of the breast cancer patient was 51.07%. The majority of the patients (151, 70.9%) presented an advanced stage at the time of diagnosis. In the bi-variable analysis, cases who were younger, of a lower educational status, at a more advanced stage, with a bigger tumor size, and a central tumor location showed a worse five-year OS compared to their counterparts (p = 0.005, 0.001, 0.004, 0.011 and 0.023, respectively). In the multivariable analysis, age was an independent predictor for the OS (HR = 3.73; 95% CI = 1.0-13.6, p = 0.046). CONCLUSION: The five-year OS of breast cancer patients in the local tertiary hospital was 51.07%. The patients' age at diagnosis was the only significant prognostic factor for the patients' survival

FAKTOR – FAKTOR YANG MEMPENGARUHI TINDAKAN KRIOTERAPI PADA INDIVIDU IVA POSITIF DI KABUPATEN TEMANGGUNG TAHUN 2018

Latar Belakang: Penyakit kanker adalah penyakit yang timbul akibat pertumbuhan tidak normal sel jaringan tubuh yang berubah menjadi sel kanker. Berdasarkan WHO, Setiap tahun 12 juta orang di dunia menderita kanker dan 7,6 juta meninggal dunia. Diperkirakan pada 2030 mencapai 26 juta orang dan 17 juta meninggal. Indonesia, tahun 2013 prevalensi tertinggi sebesar 0,8‰. Rumah sakit kanker Dharmais tahun 2010, kanker serviks 296 kasus, tahun 2011, kanker serviks 300 kasus, tahun 2012 kanker serviks 343 kasus, tahun 2013, kanker serviks 356 kasus, tahun 2014 kanker serviks 383 kasus. Kabupaten Temanggung sejak akhir tahun 2015 sampai Mei tahun 2017, pemeriksaan leher rahim sebanyak 5.323 orang terdiri dari IVA positif sebanyak 2.013 orang dan yang dilakukan krioterapi sebanyak 238 orang. Penelitian ini bertujuan untuk mengetahui faktor-faktor yang mempengaruhi tindakan krioterapi pada individu IVA positif di Kabupaten Temanggung tahun 2017.Metode: Jenis penelitian ini adalah analitik observasional dengan desain cross sectional. Sampel diambil secara simpel random sampling. Terdiri dari 356 sampel. Analisis dilakukan dengan univariat, bivariat dan multivariatHasil: Penelitian ini dilaksanakan di wilayah Kabupaten Temanggung terhadap individu IVA positif. Jumlah responden dalam penelitian ini sebanyak 356 orang responden umur ≥ 35 tahun sebanyak 198 (55,62%. Pendidikan sekolah dasar dengan tindakan krioterapi di peroleh p value 0,000; PR = 1,83 (CI 95% = 1,131-2,414). Pengetahuan dengan tindakan krioterapi di peroleh p value 0,003; PR = 0,78 (CI 95% = 0,660-0,913). Pekerjaan bertani dengan tindakan krioterapi diperoleh p value 0,005; PR = 1,34 (CI 95% = 1,120-1,567). Keterjangkauan jarak dengan tindakan krioterapi di peroleh p value 0,016; PR = 1,26 (CI 95% = 1,029-1,538). Dukungan suami tidak memberikan ijin untuk melakukan krioterapi di peroleh p value 0,018; PR = 1.48 (CI 95% = 1,219-1,799). Dukungan suami tidak mau mengantar ke puskesmas untuk melakukan krioterapi di peroleh p value 0,026; PR = 1,21 (CI 95%  = 1,031-1,428).Kesimpulan: Pendidikan ada pengaruh, pengetahuan kurang ada pengaruh risikonya 0,78 kali lebih besar dibandingkan dengan pengetahuan baik, pekerjaan, keterjangkauan jarak, dukungan suami tidak memberikan ijin ada pengaruh risikonya 1,45 kali lebih besar dibandingkan dengan dukungan suami memberikan ijin melakukan tindakan krioterapi pada individu IVA positif di Kabupaten Temanggung