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Objective: Colorectal cancer (CRC) is the world’s third most common type of cancer. Data in Indonesia based on GLOBOCAN in 2020 shows CRC in the fourth position with around 35,000 new cases each year. The pathogenesis mechanisms of CRC are complex and heterogeneous, one of which is the involvement of NRAS (Neuroblastoma Rat Sarcoma viral oncogene homolog) mutations which play a role in cell growth regulation, as well as the expression of Human epidermal growth factor receptor 2 (HER2). This study aims to assess the association of subject characteristics and NRAS mutations with HER2 expression in CRC. Methods: This research is a cross-sectional study. There were 58 patients included in this study, they were colorectal cancer patients in the Digestive Surgery division at Dr. Hassan Sadikin Hospital. Examination of NRAS mutations was carried out by Polymerase Chain Reaction (PCR) from fresh tumour tissue obtained from surgery or colonoscopy. Meanwhile, HER2 examination used the Immunohistochemistry (IHC) method of paraffin blocks for anatomical pathology examination. Result: HER2 overexpression was found in 6/58 (10.3%) patients with CRC, and from 8 subjects with NRAS mutations, only 1 subject (1.7%) showed overexpression of HER2. Univariate analysis of HER2 expression showed no significant associations to age, sex, histologic feature, tumor location, and NRAS mutations. A significant association was found between HER2 expression and stadium of the CRC with p=0.001. Conclusion: There is no association between NRAS mutations and HER2 overexpression in colorectal cancer patients.

Beban kesehatan yang ditimbulkan akibat kanker terus meningkat seiring dengan morbiditas dan mortalitas yang nyata baik di negara maju maupun berkembang. Jamur laut merupakan sumber metabolit sekunder yang berguna untuk tujuan penemuan obat. Sejumlah senyawa metabolit yang dihasilkan oleh jamur laut telah menunjukkan efek antikanker kuat. Metabolit Cytochalasin K yang dihasilkan jamur Arthrinium arundinis ZSDS1-F3 yang diisolasi dari spons laut Phakellia fusca memiliki aktivitas sitotoksik terhadap lini sel K562, A549, Huh-7, H1975, HL60, Hela, dan MOLT-4. Metabolit Disydonol A yang diproduksi oleh jamur Aspergillus sp. yang diisolasi dari spons laut Xestospongia testudinaria memiliki aktivitas sitotoksik terhadap lini sel HepG-2 and Caski. Metabolit Marilines A1 dan A2 yang dihasilkan oleh jamur Stachylidium sp. yang diisolasi dari spons laut Callyspongia cf. C. flammea memiliki aktivitas sitotoksik terhadap lini sel HLE. Dalam ulasan ini, kami menyoroti beberapa jamur yang berasal dari laut dengan metabolit yang dapat memodulasi aktivitas beberapa enzim yang berperan penting pada pertumbuhan dan metastasis sel tumor.

Background: Brain natriuretic peptide is a cardiac hormone secreted from the left ventricular myocardium due to ventricular expansion and volume overload. A recent study shows that small VSD will have risk of ventricular dysfunction in adulthood. Another complications such as endocarditis, congestive heart failure, aortic regurgitation, arrhythmia also we should be aware. Evaluations of the plasma B-type natriuretic peptide level (NT pro BNP) are currently being considered as methods to identify the possible presence of ventricular dilation in small VSD. Objective: To evaluate the change in plasma B-type natriuretic peptide after transcatheter closure of VSD. Methods: A pretest-posttest design was conducted on VSD patients before and after transcatheter closure. Plasma B-type natriuretic peptide level were measured before and 30 days after the transcatheter closure of VSD. Result: A total of 32 peri membranous VSD patients were included in this study with 62.5 % female patients (n=20) and 37.5 % male patients (n=12). A significant decrease was observed in the median NT pro BNP level when the level before closure of 1.08 (0.74 – 3.47) ng/ml was compared to the level after closure of 0.91 (0.68 – 2.07) ng/ml (p

The World Health Assembly's target in exclusive breastfeeding has not been achieved. The most common factor contributing to this problem is the perceived insufficient production of breast milk, leading to the inability to give breastmilk to her child. Milk production can be increased using some ways, such as herbal galactagogue. This article aimed to review the effectiveness of some medicinal plants as galactagogues. This study uses a literature review approach by using several sources selected based on the criteria that have been set by researchers. Based on thirteen literature, herbs reviewed in this article showed positive effects as a galactagogue. Evidence regarding its efficacy and safety is scarce. Additionally, few clinical trials exist to justify its effectiveness. Further clinical trials are needed to support these findings.

The administration of high-dose methotrexate (HD-MTX) requires an accurate monitoring of blood MTX levels to determine the regimen of leucovorin rescue and urine alkalinization to prevent toxicity. However, it is technically and logistically challenging to screen patients routinely in limited-resource settings. This study aimed to evaluate blood MTX levels at 24- and 48-hours from start of infusion in relation to clinical toxicity in childhood ALL. Methods: A prospective cohort study was conducted on 32 consecutive children with acute lymphoblastic leukemia (ALL) who had received at least one cycle of 1 g/m2 HD-MTX intravenous infusion as a part of consolidation treatment based on the 2013 Indonesian ALL Protocol. In total, 68 cycles were evaluated. Serum MTX concentrations were measured using enzyme immunoassay. MTX toxicity was categorized using common toxicity criteria (CTCAE) 3.0 version. The association between MTX level and clinical toxicity was assessed by non-parametric analysis. Results: The 24-hours MTX level was median 29.8 ng/mL (0.065 µmol/L) (IQR 8.1–390.6) with a modest decrease in 48-hours MTX serum level in all cycles (median 28.3 ng/mL and 0.062 µmol/L; IQR 0.35–28.7; p

Breast Cancer (BC) is the leading cause of cancer death in women. One BC subtype is very aggressive with amplification of human epidermal growth factor receptor 2 (HER2) protein. Although specific HER2+ targeting agents are available, most of HER2+ BC patients develop resistant to these agents. Recent studies show that metformin, is able to become anti-tumor in various cancer cells. This research aims to evaluate anti-tumor activities of metformin to HER2+ BC cells in both sensitive and resistant to trastuzumab. A series of assays were performed to evaluate metformin anti-tumor activities in HCC-1954 and SKBR-3 HER2+ BC cells. MTT assay was performed to evaluate cell death, and inhibitory concentration (IC50), while scratch assay was performed to assess inhibition of cell migration and clonogenic assay to assess cell proliferation. p

Background : Colorectal cancer is the second leading cause of mortality and the most prevalent cancer worldwide. Most patients, who come with late-stage, have ineffective treatments and some side effects in chemotherapy. Aaptos suberitoides has potential anti-cancer effects due to its bioactive compounds such as aptamine. This study aimed to evaluate the migration inhibition effect of Aaptos suberitoides fraction in HCT-116 cell line. Methods : This study was an experimental study. Aaptos suberitoides specimen was taken in Tinjil Island and fractionated with ethyl acetate. HCT-116 cell line was added with Aaptos suberitoides fraction and cellular migration activity was observed in 48 hours of which the scratch assay was performed. The gap closure area was determined with ImageJ software. Results : The data showed that a low concentration of Aaptos suberitoides fraction inhibited migration activity in HCT-116 cell line as follow; 1 and 5 mg/L Aaptos suberitoides fraction inhibit 3-4 % cancer cell migration in 24 hours, and 10-11% inhibition in 48 hours, respectively. However, 10 mg/L fraction concentration only inhibited 7-14% of the migration effect. Conclusion : Aaptos suberitoides fraction suggests insignificant migration inhibition in colorectal cancer cells and only inhibits less than 15 % HCT-116 cell line.

Colorectal cancer is one of the most diagnosed cancers in the world. KRAS mutations in colon cancer are being responsible for the progressiveness and resistance of the standard therapeutic available. Marine sponge is one the sources for chemotherapy. Stylissa carteri is a marine sponge that lives in Indonesia and its anti-cancer effects are starting to be explored nowadays. The purpose of this study was to determine the cytotoxicity and anti-proliferative effect of ethanol extract of Stylissa carteri against colon cancer cells with KRAS mutations HCT-116 cells. This was an in vitro study using colon cancer cell line HCT-116 which was tested by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue assay. The trypan blue assay was performed on control and treated cells at 72 h. The MTT assay was performed on cells which were previously incubated with Stylissa carteri extract. Sponge Stylissa carteri was taken from Pramuka island, Taman Nasional Kepulauan Seribu, Jakarta. The IC50 of ethanol extract of Stylissa carteri is 5 μg/mL (R square 0.9550) in HCT-116 cells. The trypan blue assay showed doubling time of incubated cell for 48 h was 26.10 h for control and 39.69 h for treated cells, respectively. Ethanol extract of Stylissa carteri has cytotoxic and anti-proliferative effects in HCT-116 colon cancer cells with KRAS mutation.Keywords: Colon Cancer, HCT-116, KRAS Mutation, Marine Sponge, Stylissa carteri.

The incidence of Chronic Myeloid Leukemia (CML) in the world is approximately 1.5 cases per 100,000 individuals. The level of resistance to CML treatment, imatinib in Indonesia is relatively high compared to Europe. Culturing CML cells can be used as a model for the determination of pathogenesis of CML, drug efficacy testing, and drug resistance testing. Studies using CML patients’ cells to be cultured in vitro and the methods used are rarely varied. This study aims to examine the distribution and viability of peripheral blood mononuclear cells from imatinib-resistant CML patients, expected to be a reference for mononuclear cell cultures from CML patients. This study was conducted in June-August 2019 using quantitative descriptive methods. The sample was mononuclear cells isolated from peripheral blood of three imatinib-resistant CML patients at the Hemato-Oncology Polyclinic of Hasan Sadikin Hospital, each of which was cultured in vitro using RPMI 1640 for 28 days. Distribution were seen using Giemsa staining, while viability was calculated using trypan blue. Data is processed using Microsoft Excel 2013 and Graphpad. Cell viability decreased during culture. Cell distribution had a different development pattern. Blast cells, eosinophils and basophils had presentation of between 0-5%. The percentage of lymphocyte changed between 11-31%. The percentage of neutrophil changed between 16-41%. The percentage of immature cells decreased, whereas the percentage of monocyte increased. In conclusion, cell viability decreases during the culture. Distribution of cells similar to the initial condition lasted until the 7th day and in the final phase it was only dominated by monocytes.Keywords: myeloid leukemia, chronic, cell culture, in vitro, peripheral blood mononuclear cell, cell viability.

Objective This study aimed to investigate the cytotoxicity, anti-proliferation and anti-migration effect of the ethanol extract of Aaptos suberitoides on trastuzumab-resistant HER2+ breast cancer cell line. Methods Aaptos suberitoides was collected from Tinjil Island, Banten, Indonesia, and was processed with maceration and ethanol extraction. HCC-1954 cells were treated with the ethanol extract and then followed by 3- [4, 5-dimethylthiazol-2-yl] -2.5 diphenyl tetrazolium bromide (MTT) assay to assess cytotoxicity, clonogenic assay and three-dimensional (3D) spheroid assay to evaluate anti-proliferative effect in two-dimensional and 3D model, respectively, and wound healing assay to determine anti-cell migration effect. Four parametric regression was used to analyse the IC50. Results This study revealed that the ethanol extract of Aaptos suberitoides suppressed cell viability in correlation with cell death induction. The IC50 values of the ethanol extract of Aaptos suberitoides using MTT assay and clonogenic assay were 12.0 ppm and 4.36 ppm, respectively. The extract demonstrated an inhibition effect on spheroid growth. In low concentration, the extract of Aaptos suberitoides inhibited cell migration. Furthermore, MS analysis showed that the most abundant compounds in this extract has molecular weight m/z 229.81 [M+H]+. Conclusion This study revealed that the ethanol extract of Aaptos suberitoides demonstrates cytotoxicity, anti-proliferation and anti-migration effect as well as inhibition effect on three-dimensional spheroid growth in trastuzumab-resistant HER2+ breast cancer cell line. .

Coronavirus disease 2019 (COVID-19) is the current biggest health problem that has caused pandemic in hundreds of countries worldwide Important efforts for COVID-19 prevention and management have been implemented by WHO and many countries;however, the number of new cases is still increasing The objective of this review is to formulate appropriate strategies to tackle COVID-19 pandemic using molecular mechanisms-based approach COVID-19preventive measuresaim toavoid virus entry to human cells by applying physical distancing, hand washing and personal protective equipment, maintaining good immune system by balanced nutrition and physical exercise, developing vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on comprehensive analysis on SARS-CoV-2 antigen presentation and subsequent immunological cascades, considering the patients' clinical condition including biomolecular parameters, and developing drugs by designing inhibitors for SARS-CoV-2 proteins responsible for virus replication and transcription © 2020 This is an Open Access article licensed under a Creative Commons license: Attribution 4 0 International (CC-BY) Published by Oriental Scientific Publishing Company

Background: HER2+ breast cancer is a very aggressive type of breast cancer. Although trastuzumab, specifically targeted for HER2, has been used for breast cancer treatments, some patients become resistant to trastuzumab. A marine sponge is one of the potential sources of anticancer agents. One of marine sponges commonly found in Indonesia is Stylissa carteri, but it has not been explored extensively. Objective: This study aimed to identify cytotoxic effects of the ethyl acetate fraction of Stylissa carteri on HCC-1954, HER2+ trastuzumab-resistant breast cancer cells, by assessing cell viability and determining IC50 value. Methods: This study was an experimental in vitro study conducted in The Cell Culture Laboratory, Faculty of Medicine Universitas Padjadjaran on February 2018 to June 2018. The Stylissa carteri was collected from Pramuka Island, Kepulauan Seribu National Park Jakarta. HCC-1954 cells were treated by serial concentration of fractions and were incubated for 72 hours. Cell viability were observed under a microscope and analysed with MTT assay. The IC50 value was also determined by using four parametric logistic regression (4PL) method by Sigmaplot version 12.0. Result: Data of this study showed descent of cell viability significantly when exposing the ethyl acetate fraction of Stylissa carteri. There was a decrease of 49% cell viability in 10 µg/ml of the ethyl acetate fraction of Stylissa carteri. The estimated IC50 value was 9.25 µg/ml. Conclusion: This result indicated that the ethyl acetate fraction of Stylissa carteri has cytotoxic effects on HER2+ trastuzumab-resistant breast cancer cells.

Background: The alternative device to close perimembranous ventricular septal defect (pmVSD) has been searched for better result, less complications and applicable for infants. However, the ideal device is still unavailable. We aimed to evaluate the effectiveness and outcome of transcatheter pmVSD closure using the KONAR-multi functional occluder (MFO).Methods: Clinical, procedural, follow-up data of pmVSD patients with symptom of heart failure or evidence of significant left to right shunt, growth failure, recurrent respiratory tract infection, and history of endocarditis who underwent transcatheter closure using the MFO were prospectively evaluated.Results: Between January 2016 and December 2017, there were complete records of 132 pmVSD children closed using MFO from eleven centers in Indonesia. The median of age was 4.5 (0.3–17.4) years; weight 14.8 (3.5–57) kg, defect size at the smallest part 3.4 (1.0–8.1) mm, flow ratio 1.6 (1.3–4.9), mean pulmonary artery pressure 18 (7–79) mmHg, fluoroscopy time 18 (3.8–91) and procedural time 75 (26–290) minutes. A retrograde approach was done in 41 (31%) patients. Procedures succeeded in first attempt in 126 (95.4%), failed in three and migration in three patients. Six of eight infants with congestive heart failure were closed successfully. Of 126 patients with successful VSD closure, 12 months follow-up were completed in all patients. The rate of complete occlusion at 1 month, 3 months, 6 months and 12 months after intervention were 95.2%, 97.6%, 99.2%, and 99.2%, respectively. New-onset aortic regurgitation and moderate tricuspid regurgitation developed only in five and three patients. Neither complete atrioventricular block, nor other complications occurred.Conclusion: Transcatheter closure of pmVSD using the MFO is safe, effective, and feasible in infants and children.

Background : Medical error is any kind of unplanned or out of procedure medical action. Some of them are error in selecting and prescribing drug which might cause the disease to remain, worse, or death. Prescribing error can be prevented by giving better education about pharmacology. One popular learning methods is blended learning. Truwinist Interdigital Method is a learning media innovation with bleanded learning concept designed subjects in audiovisual form. Truwinist Interdigital Method was accessible at university’s learning management system. This study aimed to evaluate the improvement of student’s pharmacological learning outcome upon Truwinist Interdigital Method. The learning outcome was students knowledge and skill on prescribing asthmatic drug. Method s : A experimental research was conducted with pretest and posttest design. Subjects were 148 medical students of Universitas Padjadjaran who were given Truwinist Interdigital Method . The learning outcome was observed using pre-test and post-test score and tested using Wilcolson test. Result s : Students’ knowledge score increased from average of 34.70±15.43 to 86.01±10.80. Students’ skill score increased from average of 25.31±12.76 to 76.93±10.66. The result showed students’ learning outcome increased significantly (p

Background and aims Coronavirus disease (COVID-19) still becomes a global burden that affected people in different groups. The aim of this study was to evaluate the association between thyroid disease and the outcome of COVID-19 patients. Method This was a meta-analysis study from articles obtained through a systematic literature search to investigate the relationship between thyroid disease and COVID-19 outcomes. Composite poor outcomes comprised of severity, mortality, intensive care unit (ICU) admission, and hospitalization. Results A total of 31339 patients from 21 studies included in this study. Thyroid disorder was associated with increased composite poor outcome (risk ratio (RR) 1.87 [95% confidence interval (CI) 1.53, 2.27], p 0.05; I2 = 32%, p

EFFORTS TO IMPROVE EARLY DETECTION OF BREAST CANCER IN CIJULANG 1 VOCATIONAL HIGH SCHOOL, PANGANDARAN REGENCY. The high mortality rate of breast cancer (BC) patients in Indonesia is associated with conditions of most patients come to doctor in an advanced stage of BC. This is due to the low BC awareness of Indonesian women. This community service program (PPM) is intended to increase knowledge of adolescent women about early detection of BC. This action was conducted by BC awareness workshop to 114 female students of Vocational High School (SMK) 1 Cijulang, Pangandaran district, West Java. The profile of participants showed that 64% of participants are 17 years old and mostly from Cijulang and Cimerak sub-districts. In addition, the majority of participants were not aware of BC, indicated by lack of knowledge of BC signs and symptoms (97%), and low confident of doing breast self-examination (BSE) (30%). Moreover, there were 7% of the participants were smoking which is known to be one of the major risk factors for BC. These findings point out conducting a program for increasing BC awareness among students. The program was managed by mini-lecture that focuses on BC risk factors, BC early detection and BSE (SADARI) using videos and simulation on a mannequin. This program was expected to have an impact on their families, indirectly. Ultimately, this will increase the finding of new cases of BC which will increase their life expectancy.

Background: The impact of weekly formative assessments on the summative performance of undergraduate medical students is not widely studied. The formative assessment began to be applied in the Undergraduate Medical Study Program, Faculty of Medicine, Padjadjaran University (Program Studi Kedokteran Fakultas Kedokteran Universitas Padjadjaran or PSK FK Unpad) in early 2020. This study aims to determine whether there is a correlation between weekly formative and summative assessment in Multidisciplinary Examination (MDE) and Structured Oral Examination (SOE).Methods: This study was conducted using a numerical correlative bivariate analysis with a cross-sectional design. The data used in this study was weekly formative assessment scores, MDE and SOE scores of Reproductive System (RPS) I and II of 138 medical student batch 2017. Results: Rank-Spearman test shows there was no significant correlation between the formative test scores and the MDE RPS I score (p>0.05) and the SOE score (p>0.05). Meanwhile, the MDE RPS II score with the formative test was found to be a significant correlation (p

Accelerated cancer cell growth requires a massive intake of amino acids. Overexpression of L-type (large) amino acid transporter 1 (LAT1) on the cancer cell membrane facilitates such a demand, which is limited in normal organs. Therefore, LAT1 overexpression is ideal as a molecular cancer therapeutic target. JPH203, a LAT1-selective non-transportable blocker, had demonstrated LAT1 inhibition in

Objective: Despite advanced treatment options available, drug resistance develops in breast cancer (BC) patients requiring novel effective drugs. Stylissa carteri, a marine sponge predominantly living in Indonesia territories, has not been extensively studied as anti-cancer. Therefore, this study targeted to assess the anti-tumor activity of the ethanol extract of S. carteri in BC cells. Methods: S. carteri was collected from Pramuka Island, at Kepulauan Seribu National Park, Jakarta, Indonesia and extracted using ethanol. Different BC cells including MDA MB 231, MDA MB 468, SKBR3, HCC-1954 and MCF-7 cells were treated with this extract for cytotoxic analysis using MTT assay. Spheroid growth assay and apoptosis assay were conducted in HCC-1954 cells. In addition, cell migration analysis and synergistic activity with doxorubicin or paclitaxel were conducted in MDA MB 231 cells. This extract was subjected also for GC-MS analysis. Results: The results show that ethanol extract of S. carteri demonstrated a cytotoxic activity in BC cells. The IC50 of this extract was lower 15 μg/ml in MDA MB 231, MDA MB 468, SKBR3, and HCC-1954 cells. Moreover, this extract inhibited spheroids growth and induced apoptosis in HCC-1954 cells. It inhibited cell migration and demonstrated a synergistic activity with doxorubicin or paclitaxel on triggering cell death in MDA MB 231 cells. Furthermore, GC-MS analysis indicated that this extract contained 1,2-Benzenediol, Dibutyl phthalate and 9,12-Octadecadienoic acid, ethyl ester. Conclusion: Our preliminary data indicate a potential anti-tumor activity of ethanol extract of S. carteri in breast cancer cells.

Indonesia merupakan negara yang mengalami kenaikan kejadian obesitas, hipertensi dan diabetes setiap tahunnya. Keadaan ini membuat meningkatnya prevalensi sindrom metabolik. Sindrom metabolik adalah kombinasi dari sejumlah kondisi, yaitu hipertensi, hiperglikemia, hiperkolesterolemia, hipertrigliserida dan peningkatan ukuran lingkar perut. Asupan energi dan pola makan yang berlebihan, peningkatan kejadian obesitas, aktivitas fisik sedentari dan riwayat risiko penyakit menjadi faktor resiko sejumlah kondisi penyebab terjadinya sindom metabolik. Kabupaten Pangandaran merupakan salah satu daerah pesisir pantai di Provinsi Jawa Barat yang secara demografis dimungkinkan tingginya konsumsi garam yang dapat memicu hipertensi. Pola makan dan aktivitas fisik yang tidak baik bagi kesehatan serta rendahnya tingkat pengetahuan dan kesadaran tentang bahaya sindrom metabolik memengaruhi jumlah kejadian sindrom metabolik. Pengabdian masyarakat ini dilakukan sebagai upaya preventif melalui pengisian kuisioner untuk mengetahui pola makan dan aktivitas fisik masyarakat kecamatan Cijulang Kabupaten Pangandaran serta pengukuran lingkar perut untuk mengetahui prevalensi resiko terjadinya sindrom metabolik. Dari 544 responden rata-rata berusia 30 tahun, 129 orang mempunyai lingkar perut yang tidak normal, 47% mengkonsumsi manis setiap hari 32% mengkonsumsi asin setiap hari dan 56% tidak olahraga setiap hari.

Background The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19. Methods Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19″ AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity. Results Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28–0.93, P = 0.02; I2: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05–2.95, P = 0.032; I2: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28–1.19, P = 0.136; I2: 24.1%, P = 0.267). Conclusion The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.

Background The report of transcatheter doubly committed subarterial ventricular septal defect closure is limited. The objective was to evaluate the efficacy and outcome of transcatheter closure of doubly committed subarterial ventricular septal defect. Methods Clinical records, procedural and early to one-year follow-up data of doubly committed subarterial ventricular septal defect patient who underwent transcatheter closure between 2013 and 2018 in Hasan Sadikin Hospital Bandung Indonesia were retrosprectively reviewed. Results There were 40 patients of doubly committed subarterial ventricular septal defect who underwent transcatheter closure, consisted of 18 female and 22 male. The median of age was 8.8 (range 2.7–48) years, weight 24 (range 10.3–70) kg, and defect size 3.1 (1.24–7.4) mm. Mean pulmonary arterial pressure 23.4 SD 5.4 mmHg and flow ratio 1.65 SD 0.28. Median of latest follow-up was 14 months. No serious complications or death. The median length-of-stay period was 3 days, without intensive care admission. Failure to attempt in 3 cases, resulted 92.5% of acute procedural success rate. The acute efficacy was 37.5%, and increased up to 92% on latest follow-up. Of 7 patients with pre-existing aortic regurgitation, three was improved, two persisted, and one progressed to moderate regurgitation. New onset mild aortic regurgitation occurred in 1 patient, which persisted in the same degree during follow-up. Conclusion Transcatheter closure of doubly committed subarterial ventricular septal defect is feasible, safe and effective as an alternative treatment to surgical closure in selected patient. The competence of the aortic valve remain the main concern and required further follow-up.

Breast cancer (BC) and cervical cancer (CC) have a high prevalence and mortality rate worldwide. Despite the availability of advanced treatment, resistance to conventional chemotherapies has emerged. Myrmecodia pendens, one of the species of Sarang Semut (local name), possess a potential of antitumor effects by inducing cell death different cancer cell entities. This study aimed to assess anti-tumor activities of n-hexane fraction of M. pendens in inhibiting cell survival and cell migration in BC and CC cells. M. pendens was extracted in methanol then fractionated using n-hexane or ethyl acetate. BC cells including MCF-7 (luminal A), HCC-1954 (HER2+) cells and CC Hela cells were treated with M. pendens extracts to evaluate cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay as well as anti-cell migration using scratch assay. We also analyzed inhibitory concentration 50 (IC50) of n-hexane fraction in BC and CC cells. We started with comparing cytotoxicity activities of methanol extract, ethyl acetate and n-hexane fractions of M. pendens. Data showed that the n-hexane fraction was the most potent inducing BC cell death. Therefore, we used the n-hexane fraction for further experiments. Interestingly, IC50 of this fraction in HCC-1954 and Hela cells were lower than in MCF-7 cells, 16; 13 and 60 ppm, respectively. Moreover, the low concentrations of n-hexane fraction inhibited HeLa cells migration, compared to control group (p

Cervical cancer is one of the most leading causes of women death. Currently, paclitaxel is still one of the main therapeutic regimens for cervical cancer patients. However, some patients developed to be paclitaxel-resistant. Hence, studies to find out the novel strategies to resolve this problem are important. Generating resistant cancer cell lines can be utilized as the potent tool to evaluate the efficacy of any therapeutic agent toward cancer drug-resistant problems. Current studies describing the methods to establish chemoresistance are lacking. Moreover, study in Indonesia conducting chemoresistance in cell line is limited. This study was aimed to elaborate the characteristics of HeLa cells during generation of paclitaxel-resistant cervical cancer cells. The parental HeLa cells were exposed to an escalating concentration of paclitaxel for a long time period. Subsequently, cells were divided into two groups for the evaluation of resistance characteristics. The values of inhibitory concentration 50 (IC50) and inhibitory concentration 90 (IC90) were analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Our data showed that the longer exposing periods of paclitaxel, the higher IC50 and IC90 values of HeLa cells are. IC90 of paclitaxel in HeLa Pac RB was increased from 69 pM, 440 pM, 2,561 pM and 10,337 pM on 0th, 1st, 2nd, 3rd and 4th months, respectively. Interestingly, the resistant cells were recovered to be paclitaxel-sensitive when they were not being continuously exposed to paclitaxel. In addition, the paclitaxel resistant cells become less sensitive against 5-FU but not doxorubicin, cisplatin and etoposide. We were able to generate cervical cancer HeLa paclitaxel-resistant cell line. These cell line could potentially be utilized for further studies in order to understand the molecular mechanisms of drug resistance in cervical cancer and as a tool for cancer drug discovery.Keywords: cervical cancer, drug resistant cell line, paclitaxel resistant cells, stepwise escalating concentration.

Background: Gd-DOTA is a micromolecular compound that is not specific for HER2+ breast cancer cells. It is not retained in the tissues and easily excreted via kidney and stool leading to suboptimal imaging. Conjugation of Gd-DOTA with trastuzumab by dendrimer will create a macromolecule and specifically bind to HER2 receptor. This study aimed to evaluate enhancing intensity of Gd-Dota-Dendrimer-Trastuzumab by Magnetic Resonance Imaging (MRI) in HER2+ breast cancer cells HCC1954 in apple scaffold. Methods: HER2+ breast cancer cell, HCC-1954 was culture in 3 dimensional culture system using apple scaffold. Intensity of contrast agents were evaluated using MRI. Cytotoxic activity of Gd-Dota-Dendrimer-Trastuzumab was evaluated in HER2+ breast cancer cells (HCC-1954 and SKBR-3) and HER2- breast cancer cell (MCF-7) using MTT assay. This study was an experimental test using Generalized Estimating Equation (GEE) method with statistical test of Generalized Linear Model (GLM) with exchangeable matrix correlation structure. Result: We confirmed that HCC-1954 cells were grown in apple scaffold and increased intensity of MRI image. Interestingly, Gd-Dota-Dendrimer-Trastuzumab tended to increase intensity of MRI image compared to Gd-Dota using HCC-1954 cells in apple scaffold, although the difference was not significant (p>0.05). Importantly, the HER2+ sensitive to trastuzumab cells, SKBR3 cells were still sensitive to Gd-Dota-Dendrimer-Trastuzumab but not the HCC-1954 and MCF-7 cells. Conclusion: Gd-Dota-Dendrimer-Trastuzumab was potentially increase MRI intensity in HER2+ breast cancer cells.

Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly because of the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival. Consistently, induced silencing of JUNB markedly decreased tumor growth in a murine MM model of the microenvironment. Subsequent gene expression profiling revealed a role for genes associated with apoptosis, DNA replication and metabolism in driving the JunB-mediated phenotype in MM cells. Importantly, knockdown of JUNB restored the response to dexamethasone in dexamethasone-resistant MM cells. Moreover, 4-hydroxytamoxifen-induced activation of a JunB-ER fusion protein protected dexamethasone-sensitive MM cells against dexamethasone- and bortezomib-induced cytotoxicity. In summary, our results demonstrate for the first time a specific role for AP-1/JunB in MM cell proliferation, survival and drug resistance, thereby strongly supporting that this transcription factor is a promising new therapeutic target in MM.

Objective : Despite advanced treatment options available for colorectal cancer, many reported resistance and unresponsiveness to conventional chemotherapeutic agents. Therefore, it is urgent to discover a novel drug for colon cancer. Sarang Semut ( Myrmecodia pendans ), an Indonesian native plant, has been studied extensively due to its anti-cancer profiles. This study aimed to evaluate the anti-tumour activity of Sarang Semut in colon cancer cells. Methods : We evaluated cytotoxic activity of methanol extract as well as n- hexane and ethyl acetate fraction towards colon cancer cell lines (Caco-2 and HCT-116 cells) utilizing 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The most potent fraction was evaluated further in inhibiting cell survival using MTT assay and cell proliferation using trypan blue exclusion assay as well as a clonogenic assay. Results : Our data showed that the n -hexane fraction of Sarang Semut induces more cell death than the methanol extract and ethyl acetate fraction. Therefore, we analyzed the n -hexane fraction further and found that the inhibitory concentration 50% (IC 50 ) of the n -hexane fraction was 24 and 30 parts per million (ppm) for Caco-2 and HCT-116 cells, respectively. Moreover, it inhibited cell growth as well as cell colony formation, in particular, shown by the plating efficiency (P

Background Molecular mechanisms leading to the adaptation of breast cancer (BC) cells to hypoxia are largely unknown. The anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) is frequently amplified in BC; and elevated Mcl-1 levels have been correlated with poor prognosis. Here we investigated the pathophysiologic role of Mcl-1 in Her2-positive BC cells under hypoxic conditions. Methods RNA interference and a novel small molecule inhibitor, EU-5346, were used to examine the role of Mcl-1 in Her2-positive BC cell lines and primary BC cells (sensitive or intrinsically resistant to Her2 inhibitors) under hypoxic conditions (using a hypoxic incubation chamber). Mechanisms-of-action were investigated by RT-PCR, mitochondrial isolation, as well as immunoprecipitation/blotting analysis, and microscopy. The specificity against Mcl-1 of the novel small molecule inhibitor EU5346 was verified in Mcl-1Δ/nullversus Mcl-1wt/wt Murine Embryonic Fibroblasts (MEFs). Proliferation, survival, and spheroid formation were assessed in response to Mcl-1 and Her2 inhibition. Results We demonstrate for a strong correlation between high Mcl-1 protein levels and hypoxia, predominantly in Her2-positive BC cells. Surprisingly, genetic depletion of Mcl-1 decreased Her2 and Hif-1α levels followed by inhibition of BC cell survival. In contrast, Mcl-1 protein levels were not downregulated after genetic depletion of Her2 indicating a regulatory role of Mcl-1 upstream of Her2. Indeed, Mcl-1 and Her2 co-localize within the mitochondrial fraction and form a Mcl-1/Her2- protein complex. Similar to genetically targeting Mcl-1 the novel small molecule Mcl-1 inhibitor EU-5346 induced cell death and decreased spheroid formation in Her2-positive BC cells. Of interest, EU-5346 induced ubiquitination of Mcl-1- bound Her2 demonstrating a previously unknown role for Mcl-1 to stabilize Her2 protein levels. Importantly, targeting Mcl-1 was also active in Her2-positive BC cells resistant to Her2 inhibitors, including a brain-primed Her2-positive cell line. Conclusion Our data demonstrate a critical role of Mcl-1 in Her2-positive BC cell survival under hypoxic conditions and provide the preclinical framework for the therapeutic use of novel Mcl-1- targeting agents to improve patient outcome in BC. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0686-4) contains supplementary material, which is available to authorized users.

Angiogenesis significantly influences disease progression in multiple myeloma (MM) patients and is correlated with adverse prognosis. The increase in vascular density within the bone marrow (BM) microenvironment is triggered by oncogene-mediated expression and secretion of pro-angiogenic growth factors and cytokines, most prominently including VEGF. Members of the AP-1 family of transcription factors (TFs) have emerged as actively pursued therapeutic targets over the past years. Our previous studies demonstrated a critical role for the AP-1 family member JunB in MM cell proliferation, survival and drug resistance. Whether JunB also contributes to MM BM angiogenesis is currently unknown. We first sought to identify correlative expression patterns of JUNB and angiogenic factors using the Oncomine software. Indeed, similar to JUNB our data identified significant induction of VEGF, VEGFB, IGF-1 and PlGF, progressing from normal plasma cells to cells from patients with monoclonal gammopathy of undetermined significance (MGUS) and MM in two independent gene expression profiling data sets. In contrast, no correlation was observed between expression of JUNB and ANGPT1, ANGPT2, SDF-1 and FGF4. Besides BM stromal cells (BMSCs) also osteoblasts (OBs) upregulate JunB protein levels in MM: stromal cell co-cultures. This effect is, at least in part, mediated by the humoral milieu, IL-6 in particular. Whether BMSC- and OB- mediated production and secretion of angiogenic factors is mediated via JunB in MM cells was investigated next. Our data show that doxycyclin- induced inhibition of BMSC: OB- mediated JunB upregulation in TetR-shJUNB/ MM.1S cells abrogated production and secretion of VEGF, VEGFB, IGF-1 and PlGF as evidenced by qPCR and ELISA assay. Similar effects were observed in MM: stromal cell co-cultures using the IL-6R inhibitor tocilizumab. Consequently, supernatant of both doxycycline- treated BMSC: Tet-shJUNB/ MM.1S and OB: Tet-shJUNB/ MM.1S co-cultures as well as tocilizumab significantly inhibited angiogenesis, as evidenced by matrigel- based tube formation as well as wound healing assays. Conversely, tamoxifen- induced JunB activity in JunB-ER/MM cells triggered the expression and secretion of angiogenic factors and angiogenesis. Importantly, the functional role of JunB on BM angiogenesis was also verified in vivo using a MM xenograft mouse model. To this purpose, immunodeficient NSG mice were inoculated subcutaneously with Tet-SCR/ MM.1S or Tet-shJUNB/ MM.1S together with BMSCs into the left and right flanks of mice, respectively, and fed with doxycycline in their drinking water for 5 weeks. Treatment with doxycycline inhibited JunB protein levels in Tet-shJUNB/ MM.1S, but not in Tet-SCR/ MM.1S and induced a significant reduction in growth and angiogenesis in tumors formed by Tet-shJUNB/ MM.1S versus control cells, as evidenced by Ki-67 and anti-CD31 staining. In summary, our findings demonstrate for the first time a role for JunB in MM bone marrow angiogenesis, thereby strongly supporting that this TF is a promising new therapeutic target in MM. Disclosures Hose: Takeda: Other: Travel grant; Sanofi: Research Funding; EngMab: Research Funding. Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Podar:Novartis: Research Funding; Eutropics: Research Funding.