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The Role of Serum IL-23 and Volatile Organic Compound Levels to RECIST 1.1 in The Evaluation of Therapeutic Response in Lung Cancer 血清 IL-23 和挥发性有机化合物水平与 RECIST 1.1 在肺癌治疗反应评估中的作用
Pub Date : 2024-03-29 DOI: 10.14499/indonesianjcanchemoprev14iss3pp171-180
Rizal Muldani Tjahyadi, U. Setyawan, Tri Wahju Astuti, Susanthy Djajalaksana, Arinto Yudi Ponco Wardoyo
The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) is the gold standard for the assessment of lung cancer progression. However, the assessment and diagnosis of early treatment failure is challenging due to the limitations of current tools, as well as the long intervals and unavoidable side effects.This study aims to correlate volatile organic compound (VOC) patterns, serum level of interleukin-23 (IL-23), and RECIST 1.1 to assess chemotherapy response in lung cancer patients at Saiful Anwar Hospital. A prospective observational study was performed to 47 lung cancer patients who received three cycles of platinum-based chemotherapy. Using the Breath Analyzer to measure certain volatile organic compounds (VOCs), the study observed that three of the seven VOCs examined, formaldehyde (CH2O), toluene (C7H8), and hexane (C6H14), showed lower levels after three cycles of chemotherapy. Furthermore, there was a negative correlation between RECIST1.1 and acetone (C3H6O) (p=0.023), while RECIST1.1 and methane (CH4) had a positive correlation (p=0.011). Moreover, a significant positive correlation was observed between IL-23 after-chemotherapy and RECIST 1.1 (p=0.000). According to this study, a correlation exists between methane, IL-23, and RECIST 1.1 after three cycles of chemotherapy. The increase in methane and IL-23 aligns with the disease progression determined by RECIST 1.1. Furthermore, The decrease in acetone after chemotherapy showed a negative correlation with RECIST1.1, consistent with disease progression.Keywords: Volatile Organic Compound, Interleukin-23, RECIST 1.1.
实体瘤反应评估标准(RECIST 1.1)是评估肺癌进展的金标准。本研究旨在将挥发性有机化合物(VOC)模式、血清白细胞介素-23(IL-23)水平和 RECIST 1.1 相关联,以评估赛福尔-安瓦尔医院肺癌患者的化疗反应。这项前瞻性观察研究针对 47 名接受了三个周期铂类化疗的肺癌患者。该研究使用呼吸分析仪测量某些挥发性有机化合物(VOC),结果发现,化疗三个周期后,所检测的七种挥发性有机化合物中有三种(甲醛(CH2O)、甲苯(C7H8)和正己烷(C6H14))的含量较低。此外,RECIST1.1 与丙酮(C3H6O)呈负相关(p=0.023),而 RECIST1.1 与甲烷(CH4)呈正相关(p=0.011)。此外,化疗后 IL-23 与 RECIST1.1 呈明显正相关(p=0.000)。根据这项研究,化疗三个周期后,甲烷、IL-23 和 RECIST 1.1 之间存在相关性。甲烷和 IL-23 的增加与 RECIST 1.1 确定的疾病进展一致。此外,化疗后丙酮的减少与 RECIST1.1 呈负相关,与疾病进展一致:挥发性有机化合物 白细胞介素-23 RECIST 1.1
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引用次数: 0
Citrus sinensis Peel Extract Synergistically Enhances the Cytotoxic Effect of Chemotherapeutic Agents on HepG2 Cells 柑橘果皮提取物可协同增强化疗药物对 HepG2 细胞的细胞毒性作用
Pub Date : 2024-03-29 DOI: 10.14499/indonesianjcanchemoprev14iss3pp151-159
Shofa Khamdanatuz Zufairo, D. Rahmawati, E. Meiyanto, R. A. Susidarti
Doxorubicin (DOX) and cisplatin (Cis), non-specific chemotherapeutic agents used for hepatocellular carcinoma (HCC), are frequently combined with synthetic or natural agents to enhance their cytotoxic effects. Citrus sinensis peel extract (CPE) serves as a natural source of flavonoids, including sinensetin (SIN), which has the potential to increase the efficacy of DOX and Cis. This study aimed to observe the effect of CPE and SIN one of CPE compounds, in enhancing liver cancer cell susceptibility to doxorubicin and cisplatin. The assays conducted in this study included a phytochemical analysis of CPE using TLC, cell viability assays against HepG2 cells using MTT assay in both single and combination forms, and cell viability assays on Vero cells. The result confirmed the presence of SIN as one of the compounds in CPE. Both CPE and SIN, when used individually, exhibited moderate cytotoxic effects on HepG2 cells with IC50 of 101.09 μg/mL and 83.13 μM, respectively, while showing no cytotoxic effect on Vero cells. Cis demonstrated significant cytotoxicity against HepG2 cells with an IC50 of 7.86 μM. DOX exerted a strong cytotoxic effect on both HepG2 and Vero cells, with the IC50 of 2.52 μM and 13.98 μM. It was observed that CPE was able to synergistically enhance the cytotoxic effects of DOX, and SIN synergistically increased the cytotoxicity of Cis, particularly against HepG2 cells, with CI<1.0.Keywords: CPE, SIN, Cisplatin, Doxorubicin, HCC.
多柔比星(DOX)和顺铂(Cis)是治疗肝细胞癌(HCC)的非特异性化疗药物,经常与合成或天然药物结合使用,以增强其细胞毒性作用。柑橘皮提取物(CPE)是黄酮类化合物的天然来源,包括山奈苷(SIN),它有可能提高 DOX 和 Cis 的疗效。本研究旨在观察 CPE 和 CPE 复合物之一 SIN 在增强肝癌细胞对多柔比星和顺铂的敏感性方面的作用。本研究中进行的检测包括使用 TLC 对 CPE 进行植物化学分析,使用 MTT 法检测单个和组合形式的 HepG2 细胞的细胞活力,以及 Vero 细胞的细胞活力检测。结果证实,SIN 是 CPE 中的一种化合物。CPE 和 SIN 单独使用时,对 HepG2 细胞有中等程度的细胞毒性作用,IC50 分别为 101.09 μg/mL 和 83.13 μM,但对 Vero 细胞无细胞毒性作用。Cis 对 HepG2 细胞具有明显的细胞毒性,IC50 为 7.86 μM。DOX 对 HepG2 和 Vero 细胞都有很强的细胞毒性作用,IC50 分别为 2.52 μM 和 13.98 μM。研究发现,CPE 能协同增强 DOX 的细胞毒性作用,SIN 能协同增强 Cis 的细胞毒性,尤其是对 HepG2 细胞,CI<1.0:CPE SIN 顺铂 多柔比星 HCC
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引用次数: 0
Cytotoxic Activity of Cambodian Leaves Extract (Plumeria acuminate) on Breast Cancer Cells and COX-2 Targeted Prediction of Its Chemical Contents 柬埔寨叶提取物(渐冻人梅)对乳腺癌细胞的细胞毒活性及其化学成分的 COX-2 靶向预测
Pub Date : 2024-03-29 DOI: 10.14499/indonesianjcanchemoprev14iss3pp199-206
Inggita Hasi Rahmah, Hayfa Salsabila Harsan, Faaza Aulia Rahman, E. Meiyanto, R. A. Susidarti
Cambodian leaves are suspected to contain stigma sterol which may target Cyclo-Oxygenase-2 (COX-2) or Estrogen Receptor (ER) to contribute to its cytotoxic activity on breast cancer cells. This study aimed to determine the potential of Cambodian leaf compounds and extracts as chemopreventive agents for luminal breast cancer with a molecular target of COX-2. Ethanol was used to extract the active compound of Cambodian leaves. The study on chemical activity against COX-2 employed molecular docking with Molecular Operating Environment (MOE) and the cytotoxic property of Cambodian leaf extract (CLE) on T47D was determined using the trypan blue exclusion method. The extraction yielded as 4.87% w/w CLE. Thin layer chromatography showed that Cambodian leaves contain sterol. Molecular docking confirmed that several sterol compounds have greater affinity to COX-2 than native ligands indicating that they are potent as COX-2 inhibitors. They are Stigmast-7-en-3-ol, Lupeol Acetate, and Lupeol carboxylic acid with docking scores of -14.3874, -13.8098, and -14.1045 kcal/mol respectively. The CLE exhibited cytotoxic activity on T47D cells with an IC50 value of 18 μg/mL. Therefore, CLE has a potential effect as a chemopreventive agent for breast cancer and potentially as a COX-2 inhibitor.Keywords: Cambodian leaf extract, breast cancer, COX-2 inhibitor, chemopreventive.
柬埔寨树叶被怀疑含有柱头固醇,这种固醇可能以环氧化酶-2(COX-2)或雌激素受体(ER)为靶点,从而对乳腺癌细胞产生细胞毒性作用。本研究旨在确定柬埔寨叶化合物和提取物作为以 COX-2 为分子靶点的腔隙型乳腺癌化学预防剂的潜力。研究使用乙醇提取柬埔寨树叶的活性化合物。针对 COX-2 的化学活性研究采用了分子操作环境(MOE)进行分子对接,并使用胰蓝排除法确定了柬埔寨叶提取物(CLE)对 T47D 的细胞毒性。萃取结果显示,柬埔寨叶提取物对 T47D 的细胞毒性为 4.87%(重量百分比)。薄层色谱法显示柬埔寨叶含有甾醇。分子对接证实,几种甾醇化合物与 COX-2 的亲和力大于原生配体,表明它们是有效的 COX-2 抑制剂。它们是石蒜甾-7-烯-3-醇、醋酸羽扇豆醇和羽扇豆醇羧酸,对接得分分别为-14.3874、-13.8098 和 -14.1045 kcal/mol。CLE 对 T47D 细胞具有细胞毒性活性,IC50 值为 18 μg/mL。因此,CLE具有作为乳腺癌化学预防剂和潜在 COX-2 抑制剂的潜在作用:柬埔寨叶提取物 乳腺癌 COX-2 抑制剂 化学预防
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引用次数: 0
Impact of Donor Age on Human Platelet Lysate Quality and its Consequential Effects on HeLa Cell Growth in the Presence of Anti-Cancer Compounds 捐献者年龄对人类血小板裂解液质量的影响及其在抗癌化合物作用下对 HeLa 细胞生长的影响
Pub Date : 2024-03-29 DOI: 10.14499/indonesianjcanchemoprev14iss3pp189-198
Diani Mentari, Gratiana Ekaningsih Wijayanti, T. Suhesti, Katon Muhammad, Ni Ken Ritchie, Diah Nurpratami
An integral aspect of anticancer experimentation involves delineating the optimal dosage of the test compound to ascertain its efficacy in targeting malignant cells. Numerous variables may influence a compound's cytotoxicity, among which is the choice of cell culture medium. Within in vitro settings, supplementary mediums are employed to foster cellular proliferation. Platelet lysate (PL) serves as a growth supplement, presenting an alternative to fetal bovine serum (FBS), primarily due to its incorporation of growth factors such as platelet-derived growth factor (PDGF), a component absents in FBS. The integrity of PL may be subject to various factors, including the age of the donor. This study sought to evaluate the impact of donor age on PL quality. Furthermore, it aimed to discern whether PL derived from platelet concentrate (PC) blood components of different age cohorts influences the IC50 value in anticancer compound assessment. Expired PCs were utilized, subsequently classified into age categories: ≤30 years, >30 years, and a combination of ages. PL analysis encompassed parameters such as pH, blood profile, protein, glucose, and cholesterol levels. The investigation scrutinized the influence of PL quality, as a cellular growth supplement, on the anticancer compound cisplatin's activity against HeLa cells. Findings indicate that donor age influenced the IC50 value of cisplatin on HeLa cells. Notably, elevated cholesterol levels and decreased pH in PL from donor ages >30 years were associated with reduced cisplatin toxicity.Keywords: Cisplatin, Donor Age, HeLa, IC50, Platelet Lysate.
抗癌实验的一个重要方面是确定试验化合物的最佳剂量,以确定其对恶性细胞的疗效。影响化合物细胞毒性的变量很多,其中包括细胞培养基的选择。在体外环境中,辅助培养基被用来促进细胞增殖。血小板裂解液(PL)可作为一种生长补充剂,是胎牛血清(FBS)的替代品,主要是因为它含有生长因子,如血小板衍生生长因子(PDGF),这是 FBS 中缺乏的成分。血小板的完整性可能受多种因素的影响,包括供体的年龄。本研究旨在评估供体年龄对血小板质量的影响。此外,研究还旨在了解不同年龄组别的血小板浓缩物(PC)血液成分是否会影响抗癌化合物评估的 IC50 值。研究人员利用过期的血小板,然后将其分为不同的年龄段:≤30 岁、大于 30 岁以及不同年龄段的组合。PL 分析包括 pH 值、血型、蛋白质、葡萄糖和胆固醇水平等参数。调查仔细研究了作为细胞生长补充剂的聚合酶质量对抗癌化合物顺铂对 HeLa 细胞活性的影响。研究结果表明,供体年龄会影响顺铂对 HeLa 细胞的 IC50 值。值得注意的是,供体年龄大于30岁的PL中胆固醇水平升高和pH值降低与顺铂毒性降低有关:顺铂 供体年龄 HeLa IC50 血小板裂解液
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引用次数: 0
Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin 橙皮素对顺铂联合治疗的三阴性乳腺癌细胞和肾细胞的细胞毒活性和衰老调节作用
Pub Date : 2024-03-29 DOI: 10.14499/indonesianjcanchemoprev14iss3pp181-188
A. N. Artanti, R. Jenie, R. Rumiyati, E. Meiyanto
Cisplatin (Cisp) is a non-specific chemotherapeutic agent for breast cancer. Hesperetin (HST), a flavanone found in various citrus fruits, exhibits bioactive properties, functioning as an antioxidant, anti-inflammatory, and anticancer agent. The objective of this research was to investigate the potential of HST as a co-chemotherapeutic agent in conjunction with Cisp, specifically focusing on its cytotoxic effects against 4T1 triple-negative breast cancer cells and senescence modulatory effect on Vero normal kidney cells. The cytotoxic effect and viability cell of HST were evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. In addition, the effect of cellular senescence inhibition on the Vero cell line was measured using senescence-associated β-galactosidase (SA-β-gal) staining. In the MTT assay, both HST and cisplatin demonstrated a reduction in the viability of 4T1 cells in a dose-dependent manner, yielding IC50 values of 498 μM and 2 μM, respectively. The co-treatment of HST and cisplatin showed an increase in sensitivity of the 4T1 cells with a combination index of <1. HST showed low cytotoxic activity against Vero cells, with IC50 values of over 500 μM. HST decreased cellular senescence induced by cisplatin exposure on Vero cells. These results indicated that HST in co-treatment with cisplatin decreased 4T1 cell viability synergistically. HST independently reduces the cellular senescence of normal cells. Consequently, HST holds promise for potential development as a co-treatment agent in combination with cisplatin for breast cancer cells, and it may also serve as an alternative for counteracting senescence in healthy tissues.Keywords: cytotoxic, senescence, hesperetin, cisplatin, breast cancer.
顺铂(Cisp)是一种治疗乳腺癌的非特异性化疗药物。橙皮素(HST)是一种存在于多种柑橘类水果中的黄烷酮,具有生物活性,可作为抗氧化剂、消炎剂和抗癌剂。本研究的目的是探讨 HST 与 Cisp 共同作为辅助化学治疗剂的潜力,特别关注其对 4T1 三阴性乳腺癌细胞的细胞毒性作用以及对 Vero 正常肾细胞的衰老调节作用。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑(MTT)试验评估了 HST 的细胞毒性作用和细胞活力。此外,还使用衰老相关的β-半乳糖苷酶(SA-β-gal)染色法检测了抑制 Vero 细胞系细胞衰老的效果。在 MTT 试验中,HST 和顺铂都以剂量依赖的方式降低了 4T1 细胞的活力,其 IC50 值分别为 498 μM 和 2 μM。HST 和顺铂联合处理后,4T1 细胞的敏感性增加,联合指数小于 1。 HST 对 Vero 细胞的细胞毒性较低,IC50 值超过 500 μM。HST 可降低顺铂暴露对 Vero 细胞诱导的细胞衰老。这些结果表明,HST 与顺铂联合处理可协同降低 4T1 细胞的活力。HST 可独立降低正常细胞的衰老。因此,HST有望发展成为一种与顺铂联合治疗乳腺癌细胞的药物,同时它也可以作为一种对抗健康组织衰老的替代药物。 关键词:细胞毒性;衰老;橙皮素;顺铂;乳腺癌。
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引用次数: 0
Chromolaena odorata L. Leaf Extract Elevates Cytotoxicity of Doxorubicin on 4T1 Breast Cancer Cells Chromolaena odorata L. 叶提取物可增强多柔比星对 4T1 乳腺癌细胞的细胞毒性
Pub Date : 2024-03-29 DOI: 10.14499/indonesianjcanchemoprev14iss3pp160-170
Amaliya Permata Putri, D. Rahmawati, Faaza Aulia Rahman, E. Meiyanto, Muthi’ Ikawati
Chemotherapeutic agents for breast cancer such as doxorubicin can attack normal cells as the side effects. Chromolaena odorata L. and its chemical content, sinensetin, have potential anticancer  and  antioxidant  properties.  The  objective  of  this  research  is  to  examine  the anticancer properties of C. odorata leaves extract and sinensetin on 4T1 triple negative breast cancer (TNBC) cells combined with doxorubicin. The MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5 diphenyltetrazolium  bromide)  assay  on  4T1  cells  was  used  to  determine  the  IC50 and the Combination  Index  (CI)  of  the  two  agents  in  combination.  Washing  out the  treatment  and determining  the  cells  viability  after  a  few  days  was done  to evaluate  the  persistence  of the  effects  to  cancer  cells.  Chromolaena odorata  extract  (COE)  obtained  was  proven  to contain  sinensetin  which  gave  a positive  signal  on  the  chromatogram.  COE  and  sinensetin were  moderately  cytotoxic  to  4T1  cells  with  IC50  value  of  53  μg/mL  and  58  μM  (21.6 μg/mL), respectively. Both compounds were synergist (CI<0.7) to strong synergist (CI<0.3) when combined with doxorubicin (IC50 90 nM = 0.05 μg/mL). COE and sinensetin exhibited moderate and not cytotoxic against Vero cells with IC50 values of 60 μg/mL and 243 μM (90.43 μg/mL), respectively. Both COE and sinensetin showed selectivity index values of >1 (1.13 and 4.19, respectively).  Moreover,  the  cytotoxic  effects  of  COE  on  4T1  cells  was  persisted  until  48  h after  removing  COE  from  the  medium,  indicating  the  tumor-suppression  potency  of  COE. Our findings strengthen the scientific basis of C. odorata leaves extract to be developed as a co-chemotherapeutics agent for doxorubicin on TNBC.Keywords: Chromolaena odorata L., breast cancer cells, doxorubicin, co-chemotherapy, kidney cells.
多柔比星等治疗乳腺癌的化疗药物会攻击正常细胞,产生副作用。Chromolaena odorata L. 及其化学成分 sinensetin 具有潜在的抗癌和抗氧化特性。 本研究的目的是检测香叶提取物和山奈苷对与多柔比星联合使用的 4T1 三阴性乳腺癌(TNBC)细胞的抗癌特性。采用 MTT(3-(4, 5-二甲基噻唑基-2)-2, 5-二苯基溴化四氮唑)法检测 4T1 细胞,以确定两种药物联合使用的 IC50 和联合指数(CI)。 几天后洗去处理并测定细胞存活率,以评估对癌细胞影响的持续性。 经证实,所获得的臭铬花提取物(COE)含有山奈苷,在色谱图上呈阳性信号。 COE 和 sinensetin 对 4T1 细胞具有中度细胞毒性,IC50 值分别为 53 μg/mL 和 58 μM(21.6 μg/mL)。这两种化合物具有协同作用(CI1 分别为 1.13 和 4.19)。 此外,从培养基中去除 COE 后,COE 对 4T1 细胞的细胞毒性作用持续到 48 小时,这表明 COE 具有抑制肿瘤的功效。我们的研究结果为C. odorata叶提取物作为多柔比星对TNBC的辅助化疗药物提供了科学依据:Chromolaena odorata L. 乳腺癌细胞 多柔比星 协同化疗 肾细胞
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引用次数: 0
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Indonesian Journal of Cancer Chemoprevention
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