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Indonesia

Cancer Statistics
Population in 2012: 244.8m
People newly diagnosed with cancer (excluding NMSC) / yr: 299,700
Age-standardised rate, incidence per 100,000 people/yr: 133.5
Risk of getting cancer before age 75:14.0%
People dying from cancer /yr: 194,500
Data from IARC GlobalCan (2012)
Indonesia Cancer Organisations and Resources
Latest Research Publications Related to Indonesia

Indonesia Cancer Organisations and Resources (7 links)


Latest Research Publications Related to Indonesia

Afriansyah A, Hamid AR, Mochtar CA, Umbas R
Targeted Therapy for Metastatic Renal Cell Carcinoma.
Acta Med Indones. 2016; 48(4):335-347 [PubMed] Related Publications
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC. In the majority of trials evaluating targeted therapy, patients were stratified according to Memorial Sloan Kattering Cancer Center (MSKCC) risk model and the recommendation of targeted treatment based on risk features. In first-line setting (no previous treatment), sunitinib, pazopanib, or bevacizumab plus IFN-α were recommended as treatment options for patient with favorable- or intermediate- risk features and clear cell histology. Patients who progressed after previous cytokine therapy would have sorafenib or axitinib as treatment options. Clear-cell mRCC with favorable- or intermediate- risk features and failure with first-line TKI therapy might be treated with sorafenib, everolimus, temsirolimus or axitinib. However, the current evidence did not show the best treatment sequencing after first-line TKI failure. In patients with poor-risk clear-cell and non-clear cell mRCC, temsirolimus was the treatment option supported by phase III clinical trial. In addition, several new drugs, nowadays, are still being investigated and waiting for the result of phase II or III clinical trial, and this might change the standard therapy for mRCC in the future.

Yusuf F, Ilyas S, Damanik HA, Fatchiyah F
Microbiota Composition, HSP70 and Caspase-3 Expression as Marker for Colorectal Cancer Patients in Aceh, Indonesia.
Acta Med Indones. 2016; 48(4):289-299 [PubMed] Related Publications
AIM: to investigate the relationship between microbiota composition with HSP70 and Caspase-3 expressions in colon tissue as an initial study to develop the candidate for early detection of colorectal cancer for Indonesian patients.
METHODS: this is a cross-sectional study on 32 patients undergoing colonoscopy; 16 patients of colorectal cancer (CRC) while the other 16 patients are not (colitis and internal hemorrhoid). The composition of microbiota in stool samples was examined using 16S rRNA Denaturing Gradient Gel Electrophoresis (DDGE) while expression of HSP70 was examined by immunohistochemistry and Caspase-3 by using Haematoxylin-Eosin(HE) staining to determine the morphological changes in colon tissue.
RESULTS: analysis of PCR-DDGE shows a different composition of microbiota between patients with CRC and non-CRC. All CRC patients showed disappearance of dominant band from Bifidobacterium groups. Histological observation based on Inter Class Correlation (ICC) test from all slide showed a high scores (5.2-9.2) in CRC patients and low scores (1.7-2.4) in non-CRC patients. HSP70 expression was increased significantly in CRC patients with the highest percentage of 84%, while expression of caspase-3 decreased with the highest percentage of 21%. Statistical analysis showed that the incidence of colorectal cancer was associated with the expression of HSP 70 (p<0.001), and Caspase 3 (p<0.001).
CONCLUSION: bifidobacterium is an important indicator for colorectal cancer patients that show disappearance of dominant band, while expression of HSP70 increased and the Caspase-3 expression decreased significantly.

Kurniawan J, Hasan I, Gani RA, Simadibrata M
Mortality-related Factors in Patients with Malignant Obstructive Jaundice.
Acta Med Indones. 2016; 48(4):282-288 [PubMed] Related Publications
AIM: to obtain survival rate and mortality-related factors of malignant obstructive jaundice patients.
METHODS: all medical records of obstructive jaundice inpatient at Cipto Mangunkusumo Hospital, Jakarta from January 2010 to December 2013 were reviewed retrospectively. The following factors were analyzed in terms of mortality: age, gender, sepsis, hypoalbumin, serum bilirubin level, serum CA 19-9 level, billiary drainage, non-ampulla Vateri carcinoma, and comorbid factors.
RESULTS: total 181 out of 402 patients were enrolled in this study with male proportion was 58.6%, and patients aged 50 years or above was 57.5%. Multivariate analysis showed that only sepsis, unsuccessful or no prior biliary drainage and Charlson comorbid score ≥4 were independent predictors of mortality. Patients with significant prognostic factors had median survival 14 days compared with overall median survival 26 days. Score ≥2 identified as the highest prognostic score threshold with sensitivity 68%, specificity 75%, and AUC on ROC curve 0.769.
CONCLUSION: sepsis, unsuccessful or no prior bilirary drainage, and Charlson comorbid score ≥4 are factors significantly associated with shortened survival in malignant obstructive jaundice patients. Prognostic score  ≥2 was determined to classify patients into high risk mortality group. Mortality of patients with those significant prognostic factors can be predicted in 76.9%.

Irawan C, Atmakusumah D, Siregar NC, et al.
Expression of Biomarkers CXCR4, IL11-RA, TFF1, MLF1P in Advanced Breast Cancer Patients with Bone Metastatic: a Diagnostic Study.
Acta Med Indones. 2016; 48(4):261-268 [PubMed] Related Publications
AIM: to analyze expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, and clinicopathology in advanced breast cancer patients with bone metastatic.
METHODS: this is a cross-sectional study. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. Immunohistochemistry and microarray analysis was performed in 81 formalin fixed paraffin embedded (FFPE) samples from 81 patients were used. Data were collected through medical records, immunohistochemistry (IHC), and microarray with nanoString nCounterTM.
RESULTS: this article is part one of a two stage reporting research results. In part one we got the results of the IHC analysis, IL11-RA with cut-off ≥103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581), p=0.010, MLF1P with cut-off ≥83.0 OR 2.784 (95% CI, 1.009-7.681), p=0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459), p<0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80% to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients.
CONCLUSION: IL11-RA, MLF1P, and ER+ were the determinants that were associated with increasing bone metastasis incidence.

Chen TH, Yen AM, Fann JC, et al.
Clarifying the debate on population-based screening for breast cancer with mammography: A systematic review of randomized controlled trials on mammography with Bayesian meta-analysis and causal model.
Medicine (Baltimore). 2017; 96(3):e5684 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality.
METHODS: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes.
RESULTS: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24-42%) and 13% (95% CI: 6-20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively.
CONCLUSION: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.

Kristanti MS, Setiyarini S, Effendy C
Enhancing the quality of life for palliative care cancer patients in Indonesia through family caregivers: a pilot study of basic skills training.
BMC Palliat Care. 2017; 16(1):4 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Palliative care in Indonesia is problematic because of cultural and socio-economic factors. Family in Indonesia is an integral part of caregiving process in inpatient and outpatient settings. However, most families are not adequately prepared to deliver basic care for their sick family member. This research is a pilot project aiming to evaluate how basic skills training (BST) given to family caregivers could enhance the quality of life (QoL) of palliative care cancer patients in Indonesia.
METHODS: The study is a prospective quantitative with pre and post-test design. Thirty family caregivers of cancer patients were trained in basic skills including showering, washing hair, assisting for fecal and urinary elimination and oral care, as well as feeding at bedside. Patients' QoL were measured at baseline and 4 weeks after training using EORTC QLQ C30. Hypothesis testing was done using related samples Wilcoxon Signed Rank. A paired t-test and one-way ANOVA were used to check in which subgroups was the intervention more significant.
RESULTS: The intervention showed a significant change in patients' global health status/QoL, emotional and social functioning, pain, fatigue, dyspnea, insomnia, appetite loss, constipation and financial hardship of the patients. Male patient's had a significant effect on global health status (qol) (p = 0.030); female patients had a significant effect on dyspnea (p = 0.050) and constipation (p = 0.038). Younger patients had a significant effect in global health status/QoL (p = 0.002). Patients between 45 and 54 years old had significant effect on financial issue (p = 0.039). Caregivers between 45 and 54 years old had significant effect on patients' dyspnea (p = 0.031).
CONCLUSIONS: Basic skills training for family caregivers provided some changes in some aspects of QoL of palliative cancer patients. The intervention showed promises in maintaining the QoL of cancer patients considering socio-economic and cultural challenges in the provision of palliative care in Indonesia.

Motoshima T, Komohara Y, Ma C, et al.
PD-L1 expression in papillary renal cell carcinoma.
BMC Urol. 2017; 17(1):8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2).
METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC).
RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen. PD-L1 expression was not significantly correlated with any clinicopathological factor, including progression-free survival and overall survival. The frequency of PD-L1-positive cases was higher in type 2 (36%) than in type 1 (22%) pRCC; however, there was no significant difference in the percentages of score 0 cases (p value = 0.084 in Chi-square test). The frequency of high PD-L1 expression cases was higher in type 2 (23%) than in type 1 (11%), and the frequency of high PD-L1 expression cases was higher in grade 3/4 (21%) than in grade 1/2 (13%). However, no significant association was found between PD-L1 expression and all clinicopathological factors in pRCC.
CONCLUSION: High expression of PD-L1 in cancer cells was potentially associated to highly histological grade of malignancy in pRCC. The evaluation of the PD-L1 protein might still be useful for predicting the efficacy of anti-cancer immunotherapy using immuno-checkpoint inhibitors, however, not be useful for predicting the clinical prognosis.

Pemayun TG
Current Diagnosis and Management of Thyroid Nodules.
Acta Med Indones. 2016; 48(3):247-257 [PubMed] Related Publications
Thyroid nodules are frequently found. Although they are often palpable, many are found incidentally during unrelated radiographic studies. Ten to 15% of thyroid nodules represents thyroid malignancy. Clinician suc as an internist/endocrinologist have to  classify the nodule, stratify the risk of thyroid cancer, performed a diagnostic work-up, provide medical / non-surgical therapy, select candidates for surgery and provide appropriate follow-up that should last a lifetime. This article provide an up-date review of diagnostic approach and management of thyroid nodules, focusing on current algorithm in lights of the most recent published American Thyroid Association thyroid nodule and differentiated thyroid cancer management guidelines.

Billy M, Sholihah H, Andanni K, et al.
Obesity as Predictor of Mortality of Colorectal Cancer: an Evidence-based Case Report.
Acta Med Indones. 2016; 48(3):242-246 [PubMed] Related Publications
AIM: to determine all-cause mortality and cancer-spesific mortality of colorectal cancer patient with obesity.
METHODS: a search was conducted on Pubmed, Proquest, Ebsco, Scopus, and Cochrane based on clinical query. The screening of title and abstract using inclusion and exclusion criteria, filtering double, and reading full text led to one useful article. This study, which is meta-analysis was critically appraised for its validity, importance and applicability.
RESULTS: the relative risk of colorectal cancer patient with pre-existing obesity having cancer-specific mortality and all-cause mortality is 1.22 (95% CI, 1.003-1.35) and 1.25 CI (95% CI, 1.14-1.3) respectively, when compared with non-obese colorectal cancer patient.
CONCLUSION: pre-existing obesity is related to increased risk of all-cause mortality and cancer-spesific mortality of in colorectal patient. Control of body weight is recommended in this patient through combination of diet, physical activity, behavior therapy, pharmacotherapy, and surgery.

Perdana NR, Mochtar CA, Umbas R, Hamid AR
The Risk Factors of Prostate Cancer and Its Prevention: A Literature Review.
Acta Med Indones. 2016; 48(3):228-238 [PubMed] Related Publications
This is a literature review study. Data was obtained from several literature reviews and journal resources that have correlation with the risk factors involved in PCa including age, ethnicity, family history, insulin-Like growth factor, sexually transmitted disease, obesity, smoking, alcohol consumption, vasectomy, and diet, and the prevention of PCa including soy, lycopene, green tea, supplementation, and exercise.Numerous epidemiologic studies have linked PCa risk to various factors, i.e. age, ethnicity, family history, insulin like-growth factors, lifestyle, diet, environmental and occupational exposures. The results of epidemiological, In vivo, in vitro, and early clinical studies suggested that selected dietary products and supplementation may play a role in PCa prevention. More studies are still needed to explore and find the risk factors and preventive methods of PCa development. It is important for clinician to ellaborate these informations for education to lower PCa risks and prevent PCa.

Trianto HB, Wardhani SO
A 44-Year-Old Man with Waldenstrom Macroglobulinemia and Bilateral Maxillary Sinusitis.
Acta Med Indones. 2016; 48(3):221-227 [PubMed] Related Publications
Waldenstrom macroglobulinemia is a chronic, indolent, lymphoproliferative disorder, which is characterized by the presence of a high macroglobulin (IgM) level, elevated serum viscosity, and the presence of a lymphoplasmacytic infiltrate in the bone marrow. Clinical manifestations may be found due to the presence of IgM paraprotein and malignant lymphoplasmacytic cell infiltration of the bone marrow and other tissues. We reported a case of male patient with Waldenstrom macroglobulinemia and bilateral maxillary sinusitis. He had received symptomatic and antibiotic treatment for his sinusitis, FFP and PRC transfusion to improve his general condition and chemotherapy with CHOP regimen as definitive treatment.

Kamal AF, Widyawarman H, Husodo K, et al.
Clinical Outcome and Survival of Osteosarcoma Patients in Cipto Mangunkusumo Hospital: Limb Salvage Surgery versus Amputation.
Acta Med Indones. 2016; 48(3):175-183 [PubMed] Related Publications
AIM: to analyze the outcome and survival rate of osteosarcoma patients in our hospital as well as the factors affecting prognosis and functional outcome.
METHODS: this is a retrospective cohort study of osteosarcoma patients in Cipto Mangunkusumo Hospital underwent limb salvage surgery (LSS), amputation, LSS + amputation, and refused surgery from year 1995 to 2014. The surgical decision was based on patient's age, staging, location, neurovascular involvement, Huvos type, functional demand, patient preference, and general condition. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) score with the maximum score of 30.
RESULTS: subjects consisted of 80 male and 52 female aged 4 to 61 year-old. They underwent limb salvage surgery (LSS) (n=37), amputation (n=42), LSS + amputation (n=2), and refused surgery (n=51). Overall 5-year cumulative survival rate was 14.6%. The 5-year survival rate for each group; LSS, amputation, combined LSS and amputation, and refused surgery was 34.8%; 15.9%; 0%; and 0%, respectively. Patients with tumor size <8 cm tend to underwent LSS compared to amputations (60.7% vs 39.3%, p=0.046). Local recurrence-free survival for LSS and amputation was 96.2% and 86.5% respectively (p=0.586). MSTS score was higher in LSS than amputation group (25.0 vs 18.5, p=0.011).
CONCLUSION: LSS had higher survival rate than amputation in osteosarcoma patients who were treated in Cipto Mangunkusumo Hospital. MSTS functional score in the LSS group was higher than amputation group.

Yulianto W, Andarwulan N, Giriwono PE, Pamungkas J
HPLC-based metabolomics to identify cytotoxic compounds from Plectranthus amboinicus (Lour.) Spreng against human breast cancer MCF-7Cells.
J Chromatogr B Analyt Technol Biomed Life Sci. 2016; 1039:28-34 [PubMed] Related Publications
The objective of this study was to identify the active compounds in Plectranthus amboinicus (Lour.) Spreng which play a role to inhibit viability of breast cancer MCF-7 cells using HPLC-based metabolomics approach. Five fractions of the plant extract were observed including ethanol, hexane, chloroform, ethyl acetate and water fraction. There were 45 HPLC chromatograms resulted from 5 fractions with 3 replications and 3 wavelengths detection. The chromatograms were compared to the data of IC50 from MTT assay of each fraction against human breast cancer MCF-7 cells using metabolomics. The OPLS analysis result promptly pointed towards a chloroform fraction at retention time of 40.16-41.28min that has the greatest contribution to the cytotoxic activity. The data of mass spectra indicated that an abietane diterpene namely 7-acetoxy-6-hydroxyroyleanone was the main compound that contributed to the cytotoxic activity. This metabolomics application method can be used as a quick preliminary guideline to uncover the most dominant compound related to the bioactivity.

Dwianingsih EK, Indrawati, Hardianti MS, et al.
Histopathological Features of Lymphoma in Yogyakarta, Indonesia.
Asian Pac J Cancer Prev. 2016; 17(9):4213-4216 [PubMed] Related Publications
The incidence and prevalence, the second most common lymphoid malignancy after leukemia, are both increasing. The distribution of lymphoma varies among sexes, age groups, and sites. In Indonesia, information about the incidence of lymphoma and its characteristics are insufficient. Therefore, this study was performed to evaluate the incidence of lymphoma and features based on age group, sex, site, clinical diagnosis, and histopathological type in Indonesia. This study is an observational analytical study with a cross-sectional design aimed to evaluate the histopathological profile of lymphoma in Yogyakarta from 2010-2014. It was based on secondary data from Anatomic Pathology Department's medical records from several hospitals and laboratories. The result showed an increased incidence of lymphoma in Yogyakarta in 2010-2014 (p=0.039). Lymphoma mostly occurred in age range 45-64 years (p=0.004), dominated by male with ratio 1.6:1. DLBCL was found to be the most common histopathological type (44.4%). Sex, age, and clinical diagnosis demonstrated statistically significant correlations with the histopathological type (p<0.001). In conclusion, the incidence of lymphoma has significantly increased from 2010-2014. There are statistically significant correlations between gender, age, and clinical diagnosis with the histopathological type of lymphoma.

Sutandyo N
New Paradigm in Treating Cancer: Right on Target.
Acta Med Indones. 2016; 48(2):139-44 [PubMed] Related Publications
Cancer prevalence is increasing every year and now cancer is the third highest cause of death in developing countries. Effective anticancer treatment can prolong life and improve the patient's quality of life. Targeted therapy is a new therapeutic modality which targets specific molecules in the cancer cell and disrupts dysregulated signaling pathways involved in carcinogenesis. Since targeted therapy does not attack normal cells, its side effects are considered low compared to chemotherapy. More than 15 drugs have been approved for treatment in various human cancers. These drugs can largely be grouped into tyrosine kinase inhibitors and monoclonal antibodies. This review will focus on the most common agents within both groups.

Hendarsih E, Fadjari TH, Oehadian A
Chemotherapy-induced Spontaneous Pneumothorax: Case Series.
Acta Med Indones. 2016; 48(2):134-8 [PubMed] Related Publications
We present 2 patients who developed spontaneous pneumothorax (SP) following rapid regression of lymphoma and rhabdomyosarcoma with lung metastases. Case 1, a 43-year old man was admitted to our hospital with dyspnea 10 days before admission. He denied any recent trauma or previous treatment for lung tuberculosis. Three weeks prior to admission, he received first cycle of CHOP for non-Hodgkin's lymphoma stage II BE. Chest X-ray consistent with right pneumothorax. After treatment with chest tube drainage for about 1 month, the patient recovered and chemotherapy could be continued without further complications. Case 2, a 35- year old man was admitted to other hospital with dyspnea and chest pain on day 4 after second cycle of systemic combined chemotherapy for rhabdomyosarcoma stage IV (lung metastases) with doxorubicin, ifosfamide, mesna, and dacarbazine. Chest X-ray showed hydropneumothorax on right and left lung. After treatment with chest tube drainage about 2 weeks, the patient recovered and chemotherapy could be continued without further complications. The mechanism of pneumothorax following chemotherapy is not clearly understood yet, however, several hypotheses have been considered: 1) the rupture of a subpleural bulla after chemotherapy; 2) the rupture of an emphysematous bulla in an over expanded portion of the lung which is partially obstructed by a neoplasm; 3) tumor lyses or necrosis due to cytotoxic chemotherapy directly induces the formation of fistula. Dyspnea and chest pain suddenly appear during successful chemotherapy for metastatic chemosensitive tumors should alert the physician to the possibility of SP. The treatment is directed toward lung re-expansion. Chemotherapy induced pneumothorax should be considered as oncologic emergency.

Koncoro H, Putra IK, Wibawa ID
Obstructive Jaundice as a Complication of Macrocystic Serous Cystadenoma of the Pancreas.
Acta Med Indones. 2016; 48(2):129-33 [PubMed] Related Publications
Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Herein, we report on a 40-year-old woman diagnosed with macrocystic serous cystadenoma who presented with obstructive jaundice. A cystic lesion in the head and body of the pancreas was revealed by abdominal computed tomography. Intraoperative pancreatic cyst aspiration ruled out mucinous cystic neoplasm which has a malignant potential. The pancreatic cyst fluid cytology was basophilic amorph materials concluded as benign cystic lesion. Internal drainage was performed instead of pancreatic resection which showed good outcome. Biliary obstruction is a rare complication of serous cystadenoma. This case describes an unusual clinical presentation of macrocystic serous cystadenoma.

Susilawati D, Sitaresmi M, Handayani K, et al.
HealthCare Providers' and Parents' Perspectives on Complementary Alternative Medicine in Children with Cancer in Indonesia.
Asian Pac J Cancer Prev. 2016; 17(7):3235-42 [PubMed] Related Publications
BACKGROUND: Complementary alternative medicine (CAM) use in children with cancer is widespread. Health care providers (HCP) need to acknowledge and address this need. This study explored and compared perspectives on CAM of HCP and parents of young patients with cancer in Indonesia.
MATERIALS AND METHODS: We conducted a crosssectional study using semistructured questionnaires in HCP and parents of childhood cancer patients at an Indonesian academic hospital.
RESULTS: A total of 351 respondents participated: 175 HCP (response rate 80%) and 176 parents (response rate 80%). Parents were more likely than HCP to think that chemotherapy can cure cancer (80% compared to 69%, P=0.013). Nearly half of all parents (46%) and HCP (45%) doubted whether CAM can cure cancer. Parents were more likely than HCP to think that CAM can be helpful in childhood cancer treatment (54% compared to 35%, P=0.003). The most recommended CAM by HCP was selfprayer (93%). Reasons for recommending CAM were: hope for improvement of the child's condition (48%), patient wants to stop treatment (42%). Most discouraged CAM by HCP was by oldsmart people (70%), the reasons being: lack of evidence for usefulness (77%), lack of CAM knowledge (75%). The proportion thinking that patients were unlikely to raise the CAM topic if they perceived that doctors were skeptical was higher in parents than in HCP (52% versus 1%) (P<0.001). Most HCP (71%) and parents (77%) acknowledged that their knowledge about safety and efficacy of CAM was inadequate (P=ns). The proportion that wanted to learn or read more about CAM was higher among parents than HCP (48% compared to 31%, P=0.002).
CONCLUSIONS: HCP and parents have different perspectives on CAM use in children with cancer. HCP should enhance their CAM knowledge and encourage open communication about CAM with parents. If doctors' skepticism is perceived, parents are unlikely to raise CAM as a topic.

Ratnasari N, Nurdjanah S, Sadewa AH, Hakimi M
The role of vascular endothelial growth factor -634 G/C and its soluble receptor on chronic liver disease and hepatocellular carcinoma.
Arab J Gastroenterol. 2016; 17(2):61-6 [PubMed] Related Publications
BACKGROUND AND STUDY AIMS: The single nucleotide polymorphism (SNP) of the vascular endothelial growth factor (VEGF) gene -634 G/C (rs2010963) influences the progression of hepatocellular carcinoma (HCC). There have been no studies on the role of VEGF SNP -634 G/C in chronic liver disease (CLD). The aim of the present study was to analyse the correlation between VEGF SNP -634 and the clinical severity of CLD and HCC.
PATIENTS AND METHODS: A cross sectional study was conducted on 182 subjects (46 HCC, 39 liver cirrhotic/LC, 38 chronic hepatitis/CH; and 57 healthy subjects). The study was conducted from 2010 to 2014 at the Dr. Sardjito Hospital Yogyakarta, Indonesia. All subjects submitted blood serum for DNA sequencing examination using primer. The clinical data of CLD and HCC were assessed, and sVEGFR-2 was examined in 149 subjects. All data were analysed using STATA programme 11.0.
RESULTS: Significant differences were observed in genotypic frequency (GG/GC/CC) between HCC, LC, CH and healthy subjects (p=0.004), but though no significant differences were observed between the G>G and C>G genotypic frequencies (p=0.337). The frequency of genotype GG was significantly higher than genotype GC or CC in HCC and was associated with declining of clinical conditions (p<0.05). No significant difference in the distribution genotypes was observed with respect to the level of sVEGFR-2 in the serum. However, we observed a significant correlation between sVEGFR-2 and clinical characteristics in LC and CH (p<0.05).
CONCLUSION: Genotype GG of the VEGF SNP -634 is the dominant genotype in severe CLD and HCC. sVEGFR-2 correlates with the disease severity but is not directly associated with the SNP -634 genotype.

Putri H, Jenie RI, Handayani S, et al.
Combination of Potassium Pentagamavunon-0 and Doxorubicin Induces Apoptosis and Cell Cycle Arrest and Inhibits Metastasis in Breast Cancer Cells.
Asian Pac J Cancer Prev. 2016; 17(5):2683-8 [PubMed] Related Publications
A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV- 0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with IC50 values of 94.9 μM and 49.0±0.2 μM, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent.

Hernowo BS, Suryanti S, Wibisono F
Correlation between EGFR Expression and Radiosensitivity in Cervical Adenocarcinoma Cases.
Asian Pac J Cancer Prev. 2016; 17(5):2535-7 [PubMed] Related Publications
BACKGROUND: Most of the cervical cancer patients, including those with cervical adenocarcinomas, come at advanced stage in the developing world so its mortality is high. Radiotherapy is one of the treatment modality for advanced stage cervical adenocarcinomas, but its efficacy depends on several prognostic factors such as the stage, histopathology, presence of organ dysfunction and expression of cellular biology markers mainly involve in cell proliferation such as the epidermal growth factor receptor (EGFR). Some research indicates that activation of EGFR in malignancy (including cervical cancer) correlates with aggressive behavior, a poor prognosis and decreasing sensitivity of radiotherapy. However, the combination between targeted therapies and radiotherapy are innovative approaches which may provide a good result. This study aimed to assess any correlation between expression of EGFR and response to radiotherapy in cervical adenocarcinoma cases.
MATERIALS AND METHODS: A total of 32 women were registered in a retrospective study period January 2007 and May 2014. Paraffin blocks from these patients were processed by classical histological techniques and for immunohistochemical staining of EGFR, scoring being accomplished according to the immunoreactive scoring (IRS) of Remmele and Stegner.
RESULTS: Among the studied molecular factors, there was significant correlation expression of EGFR with poor response to radiotherapy (p=0.0001).
CONCLUSIONS: The result of this study showed a significant correlation between expression of EGFR and sensitivity of radiation in cervical adenocarcinoma cases. Further research is n ecessary to obtain information about new therapeutic management.

Wicaksono PA, Name S, Martien R, Ismail H
Formulation and Cytotoxicity of Ribosome-Inactivating Protein Mirabilis Jalapa L. Nanoparticles Using Alginate-Low Viscosity Chitosan Conjugated with Anti-Epcam Antibodies in the T47D Breast Cancer Cell Line.
Asian Pac J Cancer Prev. 2016; 17(4):2277-84 [PubMed] Related Publications
Ribosome-inactivating protein (RIP) from Mirabilis jalapa L. leaves has cytotoxic effects on breast cancer cell lines but is less toxic towards normal cells. However, it can easily be degraded after administration so it needs to be formulated into nanoparticles to increase its resistance to enzymatic degradation. The objectives of this study were to develop a protein extract of M. jalapa L. leaves (RIP-MJ) incorporated into nanoparticles conjugated with Anti-EpCAM antibodies, and to determine its cytotoxicity and selectivity in the T47D breast cancer cell line. RIP-MJ was extracted from red-flowered M. jalapa L. leaves. Nanoparticles were formulated based on polyelectrolyte complexation using low viscosity chitosan and alginate, then chemically conjugated with anti-EpCAM antibody using EDAC based on carbodiimide reaction. RIP-MJ nanoparticles were characterised for the particle size, polydispersity index, zeta potential, particle morphology, and entrapment efficiency. The cytotoxicity of RIP-MJ nanoparticles against T47D and Vero cells was then determined with MTT assay. The optimal formula of RIP-MJ nanoparticles was obtained at the concentration of RIP-MJ, low viscosity chitosan and alginate respectively 0.05%, 1%, and 0.4% (m/v). RIP-MJ nanoparticles are hexagonal with high entrapment efficiency of 98.6%, average size of 130.7 nm, polydispersity index of 0.380 and zeta potential +26.33 mV. The IC50 values of both anti-EpCAM-conjugated and non-conjugated RIP-MJ nanoparticles for T47D cells (13.3 and 14.9 μg/mL) were lower than for Vero cells (27.8 and 33.6 μg/mL). The IC50 values of conjugated and non- conjugated RIP-MJ for both cells were much lower than IC50 values of non-formulated RIP-MJ (>500 μg/mL).

Loho IM, Hasan I, Lesmana CR, et al.
Hepatocellular Carcinoma in a Tertiary Referral Hospital in Indonesia: Lack of Improvement of One-Year Survival Rates between 1998-1999 and 2013-2014.
Asian Pac J Cancer Prev. 2016; 17(4):2165-70 [PubMed] Related Publications
BACKGROUND: The survival of hepatocellular carcinoma (HCC) patients is usually low due to late diagnosis. Cipto Mangunkusumo Hospital as the largest tertiary referral hospital in Indonesia, has recently improved its modalities for advanced HCC management, but there has not been any evaluation on any improvement in HCC patient survival.
MATERIALS AND METHODS: A retrospective analysis on 114 HCC patients in 2013-2014 were conducted and compared with the database for 77 HCC patients in 1998-1999. Clinical characteristics and treatment received were recorded and the survival of both groups was analyzed using the Kaplan-Meier method and compared using the log-rank test.
RESULTS: The percentage of HBV positive patients had increased after fifteen years from 32.5% to 67.5%. Only two patients (1.8%) in 2013-2014 were diagnosed with HCC during surveillance program. Proportions of Barcelona Clinic Liver Cancer A, B, C, and D in 2013-2014 were 1.8%, 42%, 28.1%, and 28.1%, respectively. There was an increase in the use of potentially curative treatment, such as surgical resection or combination of loco-regional therapies. The one-year survival rate increased from 24.1% in 1998-1999 to 29.4% in 2013-2014, while the median survival decreased from 146 days to 138 days, but the difference was not statistically significant (p=0.913).
CONCLUSIONS: There was no improvement in the median survival of HCC patients after fifteen years because most continued to present at late stages. There is an urgent need for a nationwide implementation of a hepatitis screening program and HCC surveillance education.

Azhar Y, Achmad D, Lukman K, et al.
Predictors of Complementary and Alternative Medicine Use by Breast Cancer Patients in Bandung, Indonesia.
Asian Pac J Cancer Prev. 2016; 17(4):2115-8 [PubMed] Related Publications
BACKGROUND: The study aimed to assess complementary and alternative medicine (CAM) use and their associated factors with breast cancer patients in Bandung, Indonesia.
MATERIALS AND METHODS: In total, 330 breast cancer patients were administered questionnaires on their CAM use and CAM predictive factors including socio-demographic parameters, clinical data and quality of life, trust in physicians, trust in hospitals, satisfaction and informational needs. Data were analyzed using univariate analysis and multivariate log regreesion analysis.
RESULTS: Overall 33.3% of patients reported use of CAM. Lower income, lower education, presence of metastasis, prolonged diagnosis, less trust in physician were found to be highly associated with CAM use.
CONCLUSIONS: CAM use by breast cancer patients can be interpreted as an attempt to explore all possible options, an expression of an active coping style, or expression of unmet needs in the cancer care continuum. Physicians need to openly discuss the use of CAM with their patients and identify whether they have other unmet supportive needs.

Anwar SL, Haryono SJ, Aryandono T, Datasena IG
Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases.
Asian Pac J Cancer Prev. 2016; 17(4):1987-91 [PubMed] Related Publications
Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.

Pradjatmo H, Pradjatmo H
Impact of Preoperative Serum Levels of CA 125 on Epithelial Ovarian Cancer Survival.
Asian Pac J Cancer Prev. 2016; 17(4):1881-6 [PubMed] Related Publications
BACKGROUND: CA125 is very helpful in treatment monitoring and detection of epithelial ovarian cancer (EOC) recurrence. However there is controversy as to its accuracy and optimal usage. What is the impact of the CA125 levels before primary surgery treatment to the survival of patients? This study aimed to detect any association of preoperative serum levels with prognosis and survival in EOC patients.
MATERIALS AND METHODS: Our cohort comprised EOC patients in Dr. Sardjito Hospital, Yogyakarta, Indonesia, who complied with follow up. To explore the effect of preoperative CA125 levels and other variables on survival Cox's regression models were applied.
RESULTS: A total of 90 cases of EOC who had surgery were available for follow up. The level of CA125 poroved to be a prognostic factor for overall survival of EOC patients, with an adjusted HR of 4.10 (p = 0.03). Adjuvant chemotherapy was another prognostic factor, 1 - 2 cycles having an adjusted HR of 0.17 (p = 0.04) and 3 - 8 cycles HR 0.39 (p = 0.06). Other factors such as age of patients adjusted HR 1.54 (p = 0.32), moderate differentiation (adjusted HR 1.61, p = 0.51) poor differentiation (adjusted HR 3.41, p = 0.15), and stage of disease (adjusted HR 1.98, p = 0.27) were statistically not significant. However, this might have been because the power of the study was low.
CONCLUSIONS: Preoperative level of CA125 is a prognostic factor for overall survival in EOC patients. The best cut-off for prognostic classification of CA125 serum level is 70 U/ml.

Gunawan S, Broeke CT, Ven Pv, et al.
Parental Experiences with Chemotherapy-Induced Alopecia among Childhood Cancer Patients in Indonesia.
Asian Pac J Cancer Prev. 2016; 17(4):1717-23 [PubMed] Related Publications
BACKGROUND: This study assessed parental experiences with chemotherapy-induced alopecia among children with cancer treated at an Indonesian academic hospital.
MATERIALS AND METHODS: Fifty parents of childhood cancer patients were interviewed using semi-structured questionnaires.
RESULTS: The moment that hair fell out was the moment that parents (84%) had to admit their child had cancer. Alopecia was a traumatizing painful experience (46%). Active strategies to hide alopecia, mainly hats, were used by 66% of children, while 34% never covered their bald head. If money had not been an issue, 40% would use another strategy. Alopecia made children limit outdoor daily activities (78%) and engagement with others (60%). Significantly more children from high-educated (95%) than low-educated (60%) parents received sympathy from other people (P=0.012). Significantly more Christian (29%) than Muslim (0%) families confirmed that alopecia lowered the quality of life (P=0.046). Most parents (82%) had no prior plans about alopecia management, yet for significantly more girls (26%) than boys (0%) such plans existed (P=0.044). Parents received most information about alopecia from other parents (66%). Parents (92%) needed more alopecia education from doctors. Of all school-attending children, 53% were bullied and 47% did not want to attend school due to alopecia. Significantly more high-educated than low-educated families received pity from teachers and pupils (94% vs. 0%, P=0.004), and acceptance by pupils (81% vs. 0%, P=0.021).
CONCLUSIONS: Alopecia is a severe, far-stretching side-effect of chemotherapy with physical, psychological and social consequences for children and parents. Parents should be better informed about occurrence and impact of alopecia. Extra attention is required to facilitate children's return to school. Health- care providers should facilitate optimal supportive care through open dialogue and provision of educational materials for parents, children and their community.

Setiawati A, Setiawati A
Celecoxib, a COX-2 Selective Inhibitor, Induces Cell Cycle Arrest at the G2/M Phase in HeLa Cervical Cancer Cells.
Asian Pac J Cancer Prev. 2016; 17(4):1655-60 [PubMed] Related Publications
Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an IC50 value of 40 μM. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.

Shintia C, Endang H, Diani K
Assessment of pathological response to neoadjuvant chemotherapy in locally advanced breast cancer using the Miller-Payne system and TUNEL.
Malays J Pathol. 2016; 38(1):25-32 [PubMed] Related Publications
BACKGROUND: Responses to neoadjuvant (before surgery) chemotherapy in locally advanced breast cancer (LABC) consist of clinical and pathological responses. Evaluating chemotherapy response is essential to predict survival rate and guide future chemotherapy. Until now, the evaluation of pathological response mainly involves quantitative assessment and is often inconsistent with clinical response. We explored the evaluation of pathological responses by both quantitative and qualitative methods, i.e. by evaluating the cellularity of tumour cells and the percentage of apoptosis.
MATERIALS AND METHOD: A cross-sectional analytical retrospective study was conducted on tissue of LABC diagnosed between 2010 and 2014 at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia Cipto Mangunkusumo Hospital and Division of Surgical Oncology, Cipto Mangunkusumo Hospital. Biopsy and resection specimens were compared to evaluate reduction in cellularity, which were subsequently categorized into stages of Miller-Payne (MP) classification. The resection specimens were stained with TUNEL and the percentage of apoptosis was calculated. Reduction in cellularity between biopsy and mastectomy specimens with TUNEL staining is evaluated as a modification of the MP method.
RESULTS: We found no association between clinical responses with percentage of apoptosis, MP pathological responses and modified MP. There was a correlation between the dead cell evaluated by MP and by modified MP (p=0.000).
CONCLUSION: Modified MP increases the degree or grading of pathological responses, but it does not improve the correlation with clinical response.

Leong KH, Looi CY, Loong XM, et al.
Cycloart-24-ene-26-ol-3-one, a New Cycloartane Isolated from Leaves of Aglaia exima Triggers Tumour Necrosis Factor-Receptor 1-Mediated Caspase-Dependent Apoptosis in Colon Cancer Cell Line.
PLoS One. 2016; 11(4):e0152652 [PubMed] Free Access to Full Article Related Publications
Plants in the Meliaceae family are known to possess interesting biological activities, such as antimalaral, antihypertensive and antitumour activities. Previously, our group reported the plant-derived compound cycloart-24-ene-26-ol-3-one isolated from the hexane extracts of Aglaia exima leaves, which shows cytotoxicity towards various cancer cell lines, in particular, colon cancer cell lines. In this report, we further demonstrate that cycloart-24-ene-26-ol-3-one, from here forth known as cycloartane, reduces the viability of the colon cancer cell lines HT-29 and CaCO-2 in a dose- and time-dependent manner. Further elucidation of the compound's mechanism showed that it binds to tumour necrosis factor-receptor 1 (TNF-R1) leading to the initiation of caspase-8 and, through the activation of Bid, in the activation of caspase-9. This activity causes a reduction in mitochondrial membrane potential (MMP) and the release of cytochrome-C. The activation of caspase-8 and -9 both act to commit the cancer cells to apoptosis through downstream caspase-3/7 activation, PARP cleavage and the lack of NFkB translocation into the nucleus. A molecular docking study showed that the cycloartane binds to the receptor through a hydrophobic interaction with cysteine-96 and hydrogen bonds with lysine-75 and -132. The results show that further development of the cycloartane as an anti-cancer drug is worthwhile.

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