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Ajeng Diantini,1,2,* Mohammed Alfaqeeh,3,* Lanny Indah Permatasari,3,* Mirna Nurfitriani,3,* Lela Durotulailah,3,* Wening Wulandari,3,* Truly Deti Rose Sitorus,4 Gofarana Wilar,1,2 Jutti Levita1,2,* 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran. University, Sumedang, West Java, 45363, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Padjadjaran University, Sumedang, West Java, 45363, Indonesia; 3Master Program in Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia; 4Department of Pharmacology and Therapy, Faculty of Medicine, Padjadjaran University, Sumedang, West Java, 45363, Indonesia*These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia, Tel +6222-84288888 Ext 3510, Email jutti.levita@unpad.ac.idAbstract: Cough and cold symptoms (CCS) are common pediatric conditions often treated with over-the-counter (OTC) medications. However, the available knowledge regarding the safety and toxicity of these medications in children is inadequate. Therefore, understanding their clinical toxicology is crucial for safeguarding children’s well-being. This narrative review highlights the importance of clinical toxicology in evaluating the safety and toxicity profile of OTC medications for treating CCS in pediatric patients. The pharmacology, clinical features, and adverse effects of various drug classes commonly found in cough and cold medications are briefly discussed. Pharmacokinetic and pharmacodynamic parameters are also examined to understand the interactions between these drugs and the body. OTC cough and cold medications often contain active ingredients such as antihistamines, decongestants, antitussives, expectorants, and analgesics-antipyretics. The combination of multiple ingredients in these products significantly increases the risk of adverse effects and unintentional overdoses. Several case studies have reported significant toxicity and even fatalities associated with the use of these medications in children. This review underscores the critical importance of clinical toxicology in evaluating the safety and toxicity profile of OTC medications employed for treating CCS in pediatric patients. The findings highlight the significance of informed clinical practice and public health policies to ensure the well-being of children using OTC cough and cold medications.Keywords: bromhexine, chlorpheniramine maleate, dextromethorphan, glyceryl guaiacolate, paracetamol, pseudoephedrine

Nur Rahayuningsih,1,2 Rano K Sinuraya,1,3,4 Yasmin Fatinah,1 Ajeng Diantini,1,4 Auliya A Suwantika1,4,5 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Faculty of Pharmacy, Universitas Bakti Tunas Husada, Tasikmalaya, Indonesia; 3Unit of Global Health, Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 4Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, Indonesia; 5Center for Health Technology Assessment, Universitas Padjadjaran, Sumedang, IndonesiaCorrespondence: Rano K Sinuraya, Email r.k.sinuraya@unpad.ac.id; r.k.sinuraya@rug.nlBackground: To date, the primary global concern has revolved around addressing the COVID-19 pandemic. However, there is a growing awareness of the pandemic’s secondary impacts on critical aspects of healthcare, such as childhood immunization programs.Objective: This study aims to assess the impact of the COVID-19 pandemic on childhood immunization programs in Indonesia, with a specific focus on performance disparities between rural and urban areas. It considers factors like access, utilization, and program workload.Methods: Data were collected from primary health cares (PHCs) in two regions in West Java Province, Indonesia, representing rural and urban areas. A descriptive analysis was conducted to compare vaccination coverage, drop-out rates, and the ratio of vaccinators per dose from 2019 to 2021 in 40 and 22 PHCs for rural and urban areas, respectively. A general linear model was employed to evaluate the differences in these parameters over the three consecutive years.Results: The results indicate fluctuations in vaccine coverage over the three years, with the most significant impact observed in 2020, particularly in rural areas. Statistical analysis revealed a significant difference in routine immunization coverage, drop-out rates, and vaccinator ratios between rural and urban areas from 2019 to 2021 (p< 0.05). In 2021, both rural and urban areas displayed significant differences in performance parameters for routine immunization and COVID-19 vaccination (p< 0.05), except in terms of coverage for IPV and COVID-19 vaccination.Conclusion: The study highlights a reduction in routine immunization coverage during the pandemic, a concerning issue that increases the risk of vaccine-preventable diseases, particularly in rural areas.Keywords: immunization coverage, dropout rate, workload, primary healthcare centers

Raden Maya Febriyanti,1,&ast; Jutti Levita,2,&ast; Ajeng Diantini2 1Department of Biology Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia; 2Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia&ast;These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia, Tel +6222-84288888 Ext 3510, Email jutti.levita@unpad.ac.idAbstract: The relationship between the immune system and metabolic diseases is complex and increasingly recognized as critical to understanding conditions like obesity, diabetes, and cardiovascular diseases. Modulation of the immune system in patients with metabolic disorders can offer several potential benefits. While the salutary impact of plant-derived bioactive compounds on metabolic and immune functions is acknowledged, there is a paucity of comprehensive reviews on the multifaceted and synergistic mechanisms through which these effects are mediated. This review elucidates the therapeutic potential of phytochemical formulations in ameliorating metabolic disorders and delineates their mechanistic implications on relevant biomarkers and immune modulation. Our analysis reveals a predominance of plant species, including Boswellia serrata, Cinnamomum cassia, Citrus bergamia, Coffea arabica, Ficus racemosa, Momordica charantia, Morus Alba, and Trigonella foenum-graecum, that have undergone clinical evaluation and have been substantiated to confer both metabolic and immunological benefits. The phytoconstituents contained in these plants exert their effects through a range of mechanisms, such as improving glucose regulation, reducing inflammatory responses, and modulating immune system. As such, these findings hold considerable promise for clinical and therapeutic translation and necessitate further empirical validation through randomized controlled trials and mechanistic elucidations to affirm the safety and efficacy of herbal formulations.Keywords: metabolic disease, immune system, phytoconstituents

Ajeng Diantini,1,&ast; R Maya Febriyanti,2,&ast; Jutti Levita1,&ast; 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia; 2Department of Biology Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia&ast;These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia, Tel +6222-84288888 Ext 3510, Email jutti.levita@unpad.ac.idAbstract: COVID‐19 caused by the infection of SARS‐CoV‐2 is still a global concern. WHO reported that from 13 March to 9 April 2023, there were 3 million new cases and approximately 23,000 deaths, mostly occurring in the South-East Asia and Eastern Mediterranean regions, which is predicted due to the new Omicron variant, Arcturus XBB.1.16. Many studies have reported the potency of medicinal plants in enhancing the function of the immune system to combat virus infection. The literature review aimed to describe the efficacy and safety of add-on plant-based drugs for COVID-19 patients. The articles were explored on the PubMed and Cochrane Library databases, and published during 2020– 2023. Twenty-two varieties of plants were used as add-on therapy for COVID-19 patients. These plants were Andrographis paniculata, Viola odorata, Withania somnifera, Zingiber officinale, Curcuma longa, Ferula foetida, Centella asiatica, Thymus vulgaris, Citrus sinensis, Eugenia caryophyllus, Boswellia carterii, Elettaria cardamomum, Salvia rosmarinus, Piper nigrum, Alstonia scholaris, Picrorhiza kurroa, Swertia chirata, Caesalpinia crista, Cucurbita maxima, Tinospora cordifolia, Ocimum sanctum, and Allium sativum. The best efficacy of an add-on therapy for COVID-19 patients was found in A. paniculata herbs as a single component in pharmaceutical dosage form or in combination with other plants. The safety of the plant has been confirmed. A. paniculata does not show interaction with remdesivir or favipiravir, however, caution and therapy drug monitoring is needed if A. paniculata is used in combination with lopinavir or ritonavir because a strong noncompetitive inhibition of CYP3A4 may occur.Keywords: adjunctive therapy, flavonoids, plant-based therapy, immunomodulatory activity, clinical studies

Komang Suma Triyasa,1 Ajeng Diantini,1,2 Melisa Intan Barliana2,3 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 3Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Melisa Intan Barliana, Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Ir. Soekarno KM. 21, Jatinangor, Bandung, 45363, Indonesia, Email melisa.barliana@unpad.ac.idAbstract: Data from globocan statistic in 2020 indicate that breast cancer has become highest incidence rate of cancer. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are known immunohistochemistry (IHC) markers that mediate cell growth and survival signaling. Furthermore, regulator proteins, receptors, and their downstream signaling pathways have emerged as critical components in breast cancer formation and proliferation, and have become well-established therapeutic targets and the core focus of breast cancer therapy research. Garcinia is a big genus in the Clusiaceae family that contains a wide spectrum of biologically active metabolites for the chemical composition of their isolated fruits, stem barks, seeds, leaves, and roots, have resulted including polyisoprenylated benzophenones, polyphenols, bioflavonoids, xanthones, lactones, and triterpenes. This review article aimed to analyze the potential of Garcinia phytochemicals as a molecular therapy of breast cancer. The results showed that phytochemicals of Garcinia (i.e., α-mangostin, Cambogin, Gambogic Acid [GA], Garcinol, Griffipavixanthone, Friedolanostane triterpenoid, Hexane, Neobractatin, 7-Epiclusianone, xanthochymol - guttiferone E, and isoxanthochymol - cycloxanthochymol) have anticancer properties, including apoptosis, inhibition of proliferation, and metastasis. This review is important to provide information regarding phytochemicals of Garcinia as an alternative treatment for breast cancer patients. This article selected 28 article researches based on inclusion criteria with the keyword “Garcinia” and “Breast cancer”, in English, and available in full text and abstract searching on PubMed.Keywords: breast cancer, Garcinia spp, molecular therapy, Indonesia

Dedy Frianto,1,2 Didik Setiawan,3 Ajeng Diantini,1,4 Auliya A Suwantika1,4 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Faculty of Pharmacy, Universitas Buana Perjuangan, Karawang, Indonesia; 3Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Purwokerto, Indonesia; 4Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Auliya A Suwantika, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia, Email auliya@unpad.ac.idBackground: Cervical cancer is the second-highest cause of death in women with cancer, which is mostly caused by human papillomavirus (HPV) infection, specifically HPV 16 and 18. Next to Pap smear and visual inspection with acetic acid, HPV vaccination is highly recommended to support preventive measures.Objective: This study aimed to determine parental acceptance of HPV vaccination in districts with high prevalence of cervical cancer and different levels of household income in West Java, Indonesia by taking several factors into account.Methods: A questionnaire was delivered to 286 parents who met the major inclusion criteria of having daughters at 5th or 6th grade of elementary schools in three selected districts: Bandung, Purwakarta and Karawang. In particular, logistic regression analysis was applied to investigate the correlation of acceptance towards HPV vaccination with sociodemographic factors.Results: Respondents in Bandung, Purwakarta and Karawang were willing to pay for HPV vaccine at a price range of US&dollar; 1.38– 20.69, US&dollar; 0.07– 34.48, and US&dollar; 1.38– 6.90, respectively. In addition, respondents’ spouse was the key person influencing their decision to vaccinate their children.Conclusion: Education level and health beliefs toward cervical cancer have significant correlation (p-value < 0.05) with acceptance towards HPV vaccination.Keywords: HPV vaccination, knowledge, health belief, attitude, willingness to pay

Dedy Frianto,1,2 Didik Setiawan,3 Ajeng Diantini,1,4 Auliya A Suwantika1,4 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Faculty of Pharmacy, Universitas Buana Perjuangan, Karawang, Indonesia; 3Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Purwokerto, Indonesia; 4Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Auliya A Suwantika, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang, 45363, Indonesia, Email auliya@unpad.ac.idBackground: In countries with limited resources, a targeted HPV vaccination strategy by focusing in selected regions is preferable to be implemented than a nationwide vaccination strategy.Objective: This study aimed to review articles on economic evaluations of HPV vaccination in countries over the world that applied targeted vaccination strategies.Methods: Approximately 1769 articles were obtained from two databases (1242 and 527 articles from PubMed and ProQuest, respectively). The inclusion criteria in this systematic review were studies about full economic evaluations of HPV vaccination in targeted area or sub-national level and written in English. Full-text screening was applied to evaluate the eligibility. Final articles obtained were referred to the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. Finally, we included only 4 articles that met all inclusion and exclusion criteria.Results: Included studies in this review focused in different targeted regions, such as Punjab State in India, Vientiane in Lao PDR, Southern Vietnam in Vietnam, and Brazilian Amazon in Brazil. From 24 criteria in the CHEERS checklist, all included studies could meet 21 criteria (87.5%). All included studies in this review applied modeling approaches, which can estimate the number of cases and treatment costs averted. Applying various settings, the results of this study showed that HPV vaccination could potentially reduce the number of cervical cancer cases by 20– 72%. Taking cervical cancer screening into account, this study showed that targeted HPV vaccination was cost-effective or even cost-saving.Conclusion: Implementation of HPV vaccination in sub-national level as the initial step before nationwide vaccination is more favorable to be implemented in countries with limited budget.Keywords: cost-effectiveness, cervical cancer, vaccine, immunization, screening

Eri Amalia,1– 3 Ajeng Diantini,1 Erwahyuni Endang Prabandari,4 Danang Waluyo,4 Anas Subarnas1 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 2Department of Pharmacology, Faculty of Science and Technology, Department of Pharmacy, Muhammadiyah University, Bandung, Indonesia; 3Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 4Research Center for Vaccine and Drug, National Research and Innovation Agency, Bogor, IndonesiaCorrespondence: Eri Amalia, Department of Pharmaceutics and Pharmaceutical Technology, Laboratory Building 1, Faculty of Pharmacy, Universitas Padjadjaran. Jl. Raya Bandung-Sumedang km.21. Jatinangor, West Java, 45363, Indonesia, Email amalia_eri@yahoo.co.id; amalia@unpad.ac.idIntroduction: A combination of chemotherapy agents is the best choice in breast cancer treatment to increase the patient survival rate. 5-fluorouracil (5-FU) is one of the drugs applied in combination with other drugs to control and delay development of cancer cells. Nevertheless, the occurrence of multidrug resistance and dose-limiting cytotoxicity have limited the efficacy of 5-FU treatment. Therefore, the discovery of new anti-breast cancer drugs should be pursued.Objective: To study potency of a promising naturally derived compound, caffeic acid phenethyl ester (CAPE), for breast cancer treatment in single and combination with 5-FU.Methods: Cytotoxicity of CAPE, 5-FU, and 5-FU+CAPE was studied by in vitro MTT experiment in MCF-7 cell line, and RT-PCR analysis was used to evaluate the change in gene expression due to the treatment. Moreover, an enzymatic assay and molecular docking analysis were applied to evaluate the possible mechanism of substance-induced apoptosis.Results: The study revealed that a single treatment of CAPE showed cytotoxicity with IC50 6.6 ± 1.0 μM and 6.5 ± 2.9 μM at 24 h and 48 h, respectively. Meanwhile, 5-FU showed cytostatic activity. The 5-FU + CAPE has a synergistic effect at 24 h treatment with a CI = 0.5 and an additive effect at 48 h treatment with CI = 1.0. CAPE was also found to enhances the mRNA expression of caspase-8 and BAX within 6 hours in combination with 5-FU compared to 5-FU treatment alone. Our study reveals a new mechanism of CAPE which is related to the inhibition of human dihydroorotate dehydrogenase (HsDHODH) with an IC50 of 120.7 ± 6.8 μM, by bound to the ubiquinone-binding site of the enzyme and could be responsible for inducing extrinsic and intrinsic apoptosis.Conclusion: This study demonstrated the cytotoxicity of CAPE potential to induce apoptosis of breast cancer MCF-7 cell line single and cytotoxic–cytostatic combination with 5-FU. Therefore, further studies to develop CAPE and its derivatives will be required to discover new candidates for breast cancer agents.Keywords: caffeic acid phenethyl ester, 5-fluorouracil, dihydroorotate dehydrogenase, DHODH, MCF-7, breast cancer

Rinto Susilo,1,2 Ajeng Diantini,2 Kiki Lukman,3 Dyah Aryani Perwitasari,4 Aan Kunaedi1 1Department of Pharmacology and Clinical Pharmacy, College of Pharmacy Muhammadiyah Cirebon, Cirebon, Indonesia; 2Faculty of Pharmacy, Padjadjaran University, Bandung, Indonesia; 3Faculty of Medicine, Padjadjaran University, Indonesia, Digestive Surgeon Consultant at Hasan Sadikin Hospital, Bandung, Indonesia; 4Faculty of Pharmacy, Ahmad Dahlan University, Yogyakarta, IndonesiaCorrespondence: Dyah Aryani Perwitasari, Faculty of Pharmacy, Ahmad Dahlan University, Prof. Dr. Soepomo Janturan, Yogyakarta, 55165, Indonesia, Tel +62 812-2965-376, Fax +62 0274563515, Email dyah.perwitasari@pharm.uad.ac.idIntroduction: Assessment of the severity of adverse drug reaction (ADR) is very rare in Indonesia. The severity of ADR can describe how serious this affects the clinical condition of the patient. In Indonesia, there are no instruments used to measure the severity of ADR.Purpose: This study aims to translate, pilot test, and validate Hartwig instruments for measuring the severity of ADR in colorectal cancer patients in Indonesia.Patients and Methods: The translation method was used forward-backward technique from English to Indonesian, then being retranslated from Indonesia to English. The instrument of Indonesian version was used to assess the severity of ADR as the effect of chemotherapy. The assessment was conducted to 10 colorectal cancer patients by 30 health workers. The test validity was done based on content validity ratio (CVR) and content validity index (CVI); meanwhile, the test reliability was based on intraclass coefficient correlation (ICC).Results: All of the results of CVR present a value of > 0.33, while the range of CVI moves between 0.8 to 1.0, which declares that the instrument is valid. The satisfactory alpha value for reliability is 0.996 with signification of 0.197 (p > 0.05) based on ANOVA analysis. Meanwhile, the ICC value of 0.896 indicates a good reliability among raters.Conclusion: Indonesian version of Hartwig Instrument can be applied in measuring the severity of ADR caused by chemotherapy in colorectal cancer patients.Keywords: chemotherapy, cancer, assessment, severity ADR

Yuni Elsa Hadisaputri,1,2 Ummi Habibah,1,2 Fajar Fauzi Abdullah,2,3 Eli Halimah,1 Mutakin Mutakin,1 Sandra Megantara,1 Rizky Abdulah,1 Ajeng Diantini1 1Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, West Java, 45363, Indonesia; 2Central Laboratory, Universitas Padjadjaran, Jatinangor, West Java, 45363, Indonesia; 3Department of Chemistry, Faculty of Mathematic and Sciences, Universitas Padjadjaran, Jatinangor, West Java, 45363, IndonesiaCorrespondence: Ajeng DiantiniFaculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang KM.21, Jatinangor, West Java, 45363, IndonesiaTel +62-22-84288888 Ext. 3510Email diantini.ajeng@gmail.comIntroduction: Breast cancer is the second most common cancer in women globally, and the incidence rate has increased annually. Traditional medicine is frequently used as a cancer treatment, and soursop or Annona muricata L (A. muricata) is a traditional medicinal plant that has been widely used as an anticancer treatment and requires more thorough study.Methods: In this research, we prepared ethanol extract and three solvents, ie, ethyl acetate, n-hexane and water fractions of A. muricata leaves and assessed their antiproliferation and cytotoxic activity on MCF7 breast cancer cells compared with that on CV1 normal kidney cells; observation of cell morphology by stained with mixture of propidium iodide and 4ʹ,6-diamidino-2-phenylindole indicated that this treatment induced an ongoing process of apoptotic cell death in MCF7 cells. To clarify the cell death mechanism via apoptosis, we assessed the mRNA expression in the caspase cascade of caspase-9, caspase-3, and PARP-1, and anti-apoptotic, Bcl-2 which mediated cytotoxic activity of extracts and ethyl acetate fractions of A. muricata leaves against MCF7 cells.Results: The ethanol extract, ethyl acetate, n-hexane, and water fractions of A. muricata leaves had IC50 values of 5.3, 2.86, 3.08, and 48.31 μg/mL, respectively, in MCF7 cells but had no activity in CV1 cells. The high cytotoxic activity of A. muricata leaves was reflected by changes in the morphology of cancer cells that appeared after 6 h exposure to A. muricata leaf extract and ethyl acetate fraction; the membrane and nucleus of cells undergoing apoptosis were characterized by the rupture and loss of membranes and nuclei. The mechanism that mediates this cytotoxic activity in MCF7 cells was mediated through a decrease in the expression of Bcl-2 mRNA and an increase in caspase-9 and caspase-3 mRNA expression.Conclusion: Therefore, the leaves of the medicinal plant A. muricata contained compounds that on extraction exerted a highly effective activity as an anticancer treatment for breast cancer via induced apoptotic cell death.Keywords: soursop, Annona muricata L., MCF7 breast cancer cell, cytotoxicity, caspase-cascade

Nadiya Nurul Afifah,1 Ajeng Diantini,1,2 Ruri Intania,3 Rizky Abdulah,1,2 Melisa I Barliana2,4 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 3Dr. H.A. Rotinsulu Lung Hospital, Bandung, Indonesia; 4Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Melisa I BarlianaDepartment of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM. 21, Jatinangor 45363, IndonesiaEmail melisa.barliana@unpad.ac.idAbstract: Previous studies have indicated that genetic variations in individuals may result in changes in gene expression and amino acids. The effect of these changes may lead to different responses to platinum-based chemotherapy. A vast response rate interval and a short survival rate indicate that the efficacy and efficiency of the selection of chemotherapy have not been optimized. This article aims to illustrate the potential relationship of various genetic polymorphisms in response to platinum-based chemotherapy for several types of cancer. This review was conducted using articles from the last three- and five-year periods (2014– 2019) that use gene polymorphism and its relationship to the efficacy of platinum-based chemotherapy as their theme. A total of 26 out of 488 relevant articles were included based on specific criteria. Through various mechanisms, genes, including ERCC1, ERCC2/XPD, XPC, XPA, XRCC1, APE-1, PARP1, OGG1, ABCC2, MRP, GSTP1, GSTM1, GSTT1, MATE1, and OCT2, have been associated with patient response to platinum-based chemotherapy. We conclude that genetic polymorphism analysis is recommended for the management of cancer so that each patient can be administered therapy based on his or her genetic profile to achieve an effective and efficient outcome.Keywords: genetic polymorphism, platinum-based chemotherapy, DNA repair, drug accumulation, drug detoxification

Melisa I Barliana,1,2 Poppy D Yolanda,1 Tina Rostinawati,1 Henry Ng,1 Sofa D Alfian,2,3 Rizky Abdulah,2,3 Ajeng Diantini2,3 1Department of Biological Pharmacy, Biotechnology Laboratory, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 3Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Melisa I BarlianaDepartment of Biological Pharmacy, Biotechnology Laboratory, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM. 21, Bandung, Jatinangor 45363, IndonesiaTel +62 22 8428 8888 Ext 3510 Email melisa.barliana@unpad.ac.idBackground: Central obesity is a risk factor for metabolic syndrome. Subjects with central obesity have a higher risk of developing type 2 diabetes and cardiovascular disease. Many conditions affect the prevalence of central obesity, including energy expenditure, aging, proinflammatory conditions, and hormonal, genetic, and ethnic differences. Polymorphism of the APM1 gene, encoding the protein adiponectin, is closely related to metabolic syndrome. Adiponectin influences fatty acid oxidation and glucose intake in muscle. Therefore, variation in the APM1 gene is associated with diabetes and obesity.Purpose: The aim of the present study was to investigate the correlation of the single-nucleotide polymorphism (SNP) of the APM1 SNP rs2241766 with body mass index (BMI) and lipid profiles in Indonesian (Bandung) subjects.Patients and methods: Genotyping of the APM1 gene was performed using the Amplification Refractory Mutation System. Whole blood and serum of 54 subjects with central obesity (waist circumference [WC] ≥90 cm) and 53 healthy subjects (WC Results: The TT and GT genotype were observed (no GG genotype) in all subjects. The TC, LDL, fasting blood glucose, and BMI did not show a significant correlation between genotype variations of APM1 with central obesity. Otherwise, subjects with central obesity with the TT genotype had lower HDL levels than those with the GT genotype (p = 0.014, significant OR 1.045; 95% CI).Conclusion: This finding suggests that the T allele of the APM1 SNP rs2241766 is dominant in the Bandung population, and subjects with the homozygous TT genotype have a higher incidence of metabolic disorder.Keywords: waist circumference, SNP, rs2241766, adiponectin, metabolic syndrome

Purpose: Individual responses to platinum-based treatment for Non-Small Cell Lung Cancer (NSCLC) are influenced by genetic polymorphisms, including Single Nucleotide Polymorphisms (SNPs). This study aimed to explore the role of ERCC2 in the Nucleotide Excision Repair (NER) pathway for platinum-based chemotherapy in NSCLC. While ERCC2 is widely studied, data for Southeast Asian populations are lacking. Addressing this gap could improve personalized treatment strategies for NSCLC in this demographic. Patients and Methods: This study recruited 82 NSCLC patients with wildtype mutations of EGFR at Dr. H.A. Rotinsulu Lung Hospital, Bandung, and Dharmais Cancer Hospital, Jakarta. Data were collected prospectively from whole blood samples and medical records, while the effectiveness of chemotherapy was assessed by evaluating the response using RECIST 1.1 criteria on fourth cycle of chemotherapy. Results: The results of this study showed the presence of genotype variation among the subjects, with frequency distribution as follows: AA genotype (82.9%), AC genotype (15.9%), and CC genotype (1.2%). The analysis of the association between ERCC2 rs13181 CC + AC versus AA with RECIST 1.1 yielded an odds ratio (OR) of 1.042 (95% CI: 0.292– 3.715; p=0.950). A multivariate analysis that included cancer stage and chemotherapy regimen as additional variables produced an adjusted odds ratio (aOR) of 0.970 (95% CI: 0.263– 3.568; p=0.963). Conclusion: This study did not find statistically significant associations between ERCC2 rs13181 polymorphisms and chemotherapy responses. However, this research highlights the presence of genetic variation within the Indonesian population, with the AA genotype being the most prevalent, which may influence chemotherapy responses. The results provided preliminary data and lay the foundation for future comprehensive cohort observational investigations. [ABSTRACT FROM AUTHOR]