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Arsenic-Based Homeopathic Preparations Induce Metabolic Disruption and Reactive Oxygen Species-Mediated Cell Death in Glioblastoma Multiforme. 砷基顺势疗法制剂诱导多形性胶质母细胞瘤代谢中断和活性氧介导的细胞死亡。
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.589
Ankit Pateriya, Chirag Kulkarni, Manendra Singh Tomar, Konica Porwal, Arun Kumar Gupta, Naibedya Chattopadhyay, Ashutosh Shrivastava

Background: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with a poor median survival rate. There is an urgent need for effective and affordable anti-cancer agents for GBM treatment. In this context, arsenic-based homeopathic preparations may serve as promising therapeutic candidates.

Objectives: This study aimed to evaluate the efficacy of Arsenicum iodatum and Arsenicum album-induced cytotoxicity in GBM cells and to investigate the underlying mechanisms of action in the U-87-MG and LN-229 cell lines.

Results: Treatment with varying concentrations of Arsenicum iodatum and Arsenicum album resulted in dose- and time-dependent inhibition of GBM cells growth in U87-MG and LN-229. These preparations induced distinct morphological changes and cell death in both GBM cell lines. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics revealed significant alterations in the key metabolic pathways. A total of 107 metabolites were quantified. Univariate analysis identified 73 and 30 significantly altered metabolites in Arsenicum album-treated U-87-MG and LN-229 cells, respectively. Meanwhile, U-87 showed 69 and LN-229 showed 50 significantly affected metabolites in the Arsenicum iodatum-treated groups. In GBM cells treated with Arsenicum album and Arsenicum iodatum, glycine and serine, which are involved in redox balance, were altered, while branched-chain amino acids (valine, leucine, isoleucine)- essential for protein synthesis and mTOR signaling- were downregulated. Changes were also observed in nucleotide sugar, purine, and nicotinate/nicotinamide metabolism. The findings suggest that both agents cause strong metabolic disruptions, potentially contributing to their anti-cancer effects. Biochemical assays confirmed increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential following treatment with these arsenic based homeopathic preparation.

Conclusion: Arsenicum iodatum and Arsenicum album exhibit growth-inhibitory effects on GBM cells, likely through metabolic disruption and ROS-mediated cell death. Further studies are warranted to elucidate the precise mechanisms of cell death and to evaluate their efficacy and safety in vivo.

背景:多形性胶质母细胞瘤(GBM)是一种侵袭性很强的脑癌,中位生存率很低。迫切需要有效和负担得起的抗癌药物来治疗GBM。在这种情况下,基于砷的顺势疗法制剂可能作为有希望的治疗候选者。目的:本研究旨在评价碘砷和砷专辑对GBM细胞的毒性作用,并探讨其对U-87-MG和LN-229细胞系的作用机制。结果:不同浓度碘化砷和碘化砷对U87-MG和LN-229的GBM细胞生长有剂量依赖性和时间依赖性的抑制作用。这些制剂在两种GBM细胞系中诱导了明显的形态变化和细胞死亡。基于气相色谱-质谱(GC-MS)的代谢组学揭示了关键代谢途径的显著变化。共测定了107种代谢物。单变量分析发现,砷处理过的U-87-MG和LN-229细胞中,分别有73和30种代谢物发生了显著变化。同时,在碘砷处理组中,U-87和LN-229的代谢物分别有69和50个受到显著影响。在砷和碘化砷处理的GBM细胞中,参与氧化还原平衡的甘氨酸和丝氨酸被改变,而支链氨基酸(缬氨酸、亮氨酸、异亮氨酸)——蛋白质合成和mTOR信号传导所必需的——被下调。核苷酸糖、嘌呤和烟酸/烟酰胺代谢也发生了变化。研究结果表明,这两种药物都会导致强烈的代谢紊乱,可能有助于它们的抗癌作用。生化分析证实,使用这些砷基顺势疗法制剂治疗后,活性氧(ROS)水平升高,线粒体膜电位降低。结论:碘砷和砷相册对GBM细胞具有生长抑制作用,可能是通过代谢破坏和ros介导的细胞死亡。需要进一步的研究来阐明细胞死亡的确切机制,并评估其在体内的有效性和安全性。
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引用次数: 0
Clausenidin from Clausena excavata Burm. causes Apoptosis of Liver Cancer in Mice. Clausenidin源自Clausena excavata Burm。引起小鼠肝癌细胞凋亡。
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.481
Peter M Waziri, Richard Auta, Mustapha U Imam, Ben A Chindo, Zakari Ladan, Zainab Kasim Mohammed, Samson Wayah, Jaafar Mohammed Sani, Godwin I Ayuba, Oluwafemi T Ige, Daniel Tyoapine, Abel Agbaji

Background: Clausenidin is a pyranocoumarin that was isolated from the roots of Clausena excavata Burm. Previously, the pure clausenidin crystals were successfully used to treat HepG2 cells (liver cancer) in vitro; however, no in vivo study had been conducted to support these findings. Therefore, the current study was designed to investigate the in vivo anti-liver cancer effect of pure clausenidin in hepatocellular carcinoma-induced BALB/c mice.

Method: DNA fragmentation, caspases, and histological assays were conducted to evaluate the cytotoxic effect of the pure clausenidin, while real-time qPCR was performed to monitor the expression of apoptosis-inducing genes in the clausenidin-treated mice.

Result: Clausenidin significantly (p<0.05) decreased the liver damage-induced levels of alanine and aspartate aminotransferases and also caused fragmentation of the genomic DNA of the tumors. This was followed by a significant increase (p<0.05) in the expression of caspases 3, 8 and 9 proteins in the clausenidin-treated mice. In addition, clausenidin upregulated the expression of  pro-apoptotic genes associated with the extrinsic and intrinsic pathways. However, it was observed that clausenidin may have inhibited angiogenesis by downregulating the expression of the VEGF gene in the treated mice.

Conclusion: Therefore, clausenidin can be potentially used as an anti-liver cancer agent.

背景:克劳斯尼丁是从克劳斯纳(Clausena excavata Burm)根中分离得到的吡喃香豆素。此前,纯clausenidin晶体已成功用于体外治疗HepG2细胞(肝癌);然而,没有进行体内研究来支持这些发现。因此,本研究旨在探讨纯克劳塞尼定对肝细胞癌诱导的BALB/c小鼠体内的抗肝癌作用。方法:采用DNA片段法、caspase法和组织学法评价纯克劳斯尼丁的细胞毒作用,同时采用实时荧光定量pcr法监测克劳斯尼丁处理小鼠细胞凋亡诱导基因的表达。结论:克劳森尼定具有较好的抗肝癌作用。
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引用次数: 0
Four Gene Polymorphisms as Potential Predictive Biomarkers for Lung Cancer Susceptibility and Therapeutic Response in Iraqi Patients: A Pharmacogenetic Case-Control Study. 四种基因多态性作为伊拉克患者肺癌易感性和治疗反应的潜在预测性生物标志物:一项药物遗传学病例对照研究
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.737
Mohammed Ouda Orabiy, Doaa Hadi Chyad, Wisam Hindawi Hoidy

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with limited genetic data available on Middle Eastern populations. This study investigated four novel genetic variants CYPHER rs7834621, METOX1 rs9284659, DRUGRES2 rs4521739, and TOXMET3 rs8823471 for their association with lung cancer risk and treatment response in Iraqi patients.

Methods: Between January 2024 and September 2024, we recruited 265 tissue-confirmed lung cancer patients and 310 healthy controls from Al-Diwaniyah Teaching Hospital. DNA was extracted from blood samples and genotyped using tetra-ARMS-PCR. Logistic regression was used to analyze variant-cancer risk associations. Pharmacogenetic analysis included 198 patients receiving trastuzumab, doxorubicin, paclitaxel, and cyclophosphamide chemotherapy, with response measured by RECIST criteria.

Results: All four genetic variants showed significant associations with lung cancer risk. The CYPHER rs7834621 GG genotype was associated with the highest disease risk (adjusted OR = 2.21, 95% CI: 1.31-3.73, p = 0.003). Allele frequencies were population-specific when compared to other cohorts. Pharmacogenetic analysis revealed treatment response associations, with DRUGRES2 rs4521739 TT genotype demonstrating superior response rates compared to CC genotype (68.4% vs 31.6%, p < 0.001). Haplotype analysis identified specific gene combinations that increased disease susceptibility.

Conclusions: These novel SNPs are associated with both lung cancer risk and treatment response in Iraqi patients, potentially serving as biomarkers for risk stratification and personalized therapy guidance in this population.

背景:肺癌仍然是世界范围内癌症相关死亡的主要原因,中东人群的遗传数据有限。本研究研究了四个新的基因变异CYPHER rs7834621、METOX1 rs9284659、DRUGRES2 rs4521739和TOXMET3 rs8823471与伊拉克患者肺癌风险和治疗反应的关系。方法:2024年1月至2024年9月,我们从Al-Diwaniyah教学医院招募了265名组织确诊的肺癌患者和310名健康对照。从血液样本中提取DNA,并使用四元- arms - pcr进行基因分型。采用Logistic回归分析变癌风险关联。药物遗传学分析包括198例接受曲妥珠单抗、阿霉素、紫杉醇和环磷酰胺化疗的患者,通过RECIST标准测量疗效。结果:所有四种基因变异均与肺癌风险显著相关。CYPHER rs7834621 GG基因型与最高疾病风险相关(校正OR = 2.21, 95% CI: 1.31-3.73, p = 0.003)。与其他队列相比,等位基因频率具有人群特异性。药物遗传学分析显示治疗反应相关,与CC基因型相比,DRUGRES2 rs4521739 TT基因型表现出更高的反应率(68.4% vs 31.6%, p < 0.001)。单倍型分析确定了增加疾病易感性的特定基因组合。结论:这些新的snp与伊拉克患者的肺癌风险和治疗反应相关,可能作为该人群风险分层和个性化治疗指导的生物标志物。
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引用次数: 0
Gene Expression of MicroRNA-205, FGF2 and CARMA3 in Colorectal Cancer in Iraqi Patients. 伊拉克结直肠癌患者MicroRNA-205、FGF2和CARMA3的基因表达
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.509
Nada Nizar Kadhum, Noora Mustafa Kareem, Asmaa Mhmood Salman, Mohanad Kareem Aneed

Background: Colorectal cancer (CRC) is a growing global health concern. This study focuses on evaluating the gene expression of FGF2, CARMA3, and MicroRNA205 (miR205) as potential blood-based biomarkers for early CRC diagnosis by distinguishing patients from healthy controls.

Materials and methods: Blood samples from 80 colorectal cancer (CRC) patients and 40 healthy controls were analyzed using qRT- PCR to measure target gene expression. ROC curve analysis was performed to evaluate diagnostic accuracy, including sensitivity, specificity, and Area Under the Curve (AUC) values.

Results: MicroRNA-205 revealed downregulation in CRC patients, with an AUC of 0.7, sensitivity of 91%, and specificity of 58%. AUC values for Fibroblast Growth Factor 2 (FGF2) and Caspase Recruitment Domain Family Member 3 (CARMA3) were 0.74 and 0.77, respectively, indicating differential expression. All markers displayed modest specificity, but CARMA3 showed the highest diagnostic accuracy with 95% sensitivity. Gene expression fold change for miR-205 showed downregulation 0.3, FGF2 also showed downregulation 0.4 and CARMA3 showed slight upregulation 1.2.

Conclusion: The results suggest that miR-205, FGF2, and CARMA3 may serve as potential biomarkers for the identification of colorectal cancer (CRC), particularly when used in multi-marker panels to improve diagnostic accuracy. Their clinical utility should be confirmed through additional validation in larger cohorts.

背景:结直肠癌(CRC)是一个日益严重的全球健康问题。本研究的重点是评估FGF2、CARMA3和MicroRNA205 (miR205)的基因表达,作为区分患者和健康对照的早期CRC诊断的潜在血液生物标志物。材料与方法:采用qRT- PCR检测80例结直肠癌患者和40例健康对照者的血液中靶基因的表达。进行ROC曲线分析以评估诊断的准确性,包括敏感性、特异性和曲线下面积(AUC)值。结果:MicroRNA-205在结直肠癌患者中表达下调,AUC为0.7,敏感性为91%,特异性为58%。成纤维细胞生长因子2 (FGF2)和Caspase募集结构域家族成员3 (CARMA3)的AUC值分别为0.74和0.77,表明差异表达。所有标记均显示适度的特异性,但CARMA3显示最高的诊断准确性,灵敏度为95%。基因表达折叠变化miR-205下调0.3,FGF2也下调0.4,CARMA3轻微上调1.2。结论:研究结果表明,miR-205、FGF2和CARMA3可能作为鉴定结直肠癌(CRC)的潜在生物标志物,特别是在多标志物组合中使用以提高诊断准确性时。它们的临床应用应通过在更大的队列中进一步验证来证实。
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引用次数: 0
Clinical Significance of the S348l Mutation in BCR-ABL as a Dominant Variant in Indonesian CML Patients Under Tyrosine Kinase Inhibitor Therapy: A Cohort Study. 酪氨酸激酶抑制剂治疗下印尼CML患者BCR-ABL中S348l突变为显性变异的临床意义:一项队列研究
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.715
Tutik Harjianti, Wahyudi Pabbabari, Fachruddin Benyamin, Sahyuddin Saleh, Rahmawati Minhajat, Dimas Bayu, Arifin Seweng

Objective: Chronic myeloid leukemia (CML) is characterized by the translocation of chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) have markedly improved CML outcomes. Yet, resistance may develop due to mutations in the BCR-ABL kinase domain, particularly in the ATP-binding loop (P-loop), activation loop (A-loop), catalytic domain, and direct binding site. This study aimed to evaluate the relationship between BCR-ABL kinase domain mutations, hematological response, and overall survival among CML patients receiving TKI therapy at Wahidin Sudirohusodo General Hospital, Makassar.

Methods: A prospective cohort study was conducted from March 2022 to July 2023 at the Hematology-Oncology outpatient clinic. Among 312 patients, 22 were classified as non-responders (no hematological response within three months) and 290 as responders. Forty-four patients (22 responders and 22 non-responders) underwent mutation analysis, and survival outcomes were compared. Statistical analysis was performed using SPSS.

Results: Of the 44 patients, 11 harbored BCR-ABL mutations: S348L (n=6), T315I (n=4), and Y253F (n=1). All mutations were identified exclusively in the non-responder group. Mortality was significantly higher in non-responders than responders (p<0.05), and among non-responders with mutations compared to those without (p<0.01). Six-month survival rates were 65% for S348L, 50% for T315I, and 0% for Y253F, though survival differences between mutation types were not statistically significant (p=0,641).

Conclusion: CML patients achieving early hematological response to TKI therapy had significantly better survival outcomes. In contrast, non-responders, particularly those harboring BCR-ABL kinase domain mutations, demonstrated poorer survival. The S348L mutation was the most common variant in this cohort. Early mutation detection may help guide therapeutic adjustments and improve outcomes in TKI-resistant CML.

目的:慢性髓性白血病(Chronic myeloid leukemia, CML)以9号和22号染色体易位为特征,导致BCR-ABL融合基因的产生。酪氨酸激酶抑制剂(TKIs)可以显著改善CML的预后。然而,由于BCR-ABL激酶结构域的突变,特别是atp结合环(p环)、激活环(a环)、催化结构域和直接结合位点的突变,可能会产生耐药性。本研究旨在评估在望加锡Wahidin Sudirohusodo总医院接受TKI治疗的CML患者中BCR-ABL激酶结构域突变、血液学反应和总生存率之间的关系。方法:一项前瞻性队列研究于2022年3月至2023年7月在血液肿瘤学门诊进行。312例患者中,22例为无反应(3个月内无血液学反应),290例为反应。44名患者(22名应答者和22名无应答者)进行了突变分析,并比较了生存结果。采用SPSS进行统计分析。结果:44例患者中,11例携带BCR-ABL突变:S348L (n=6)、T315I (n=4)和Y253F (n=1)。所有突变仅在无应答组中被识别。无应答者的死亡率明显高于应答者(p结论:TKI治疗早期血液学应答的CML患者具有明显更好的生存结果。相比之下,无应答者,特别是那些携带BCR-ABL激酶结构域突变的患者,表现出较差的生存率。S348L突变是该队列中最常见的变异。早期突变检测可能有助于指导tki耐药CML的治疗调整和改善预后。
{"title":"Clinical Significance of the S348l Mutation in BCR-ABL as a Dominant Variant in Indonesian CML Patients Under Tyrosine Kinase Inhibitor Therapy: A Cohort Study.","authors":"Tutik Harjianti, Wahyudi Pabbabari, Fachruddin Benyamin, Sahyuddin Saleh, Rahmawati Minhajat, Dimas Bayu, Arifin Seweng","doi":"10.31557/APJCP.2026.27.2.715","DOIUrl":"https://doi.org/10.31557/APJCP.2026.27.2.715","url":null,"abstract":"<p><strong>Objective: </strong>Chronic myeloid leukemia (CML) is characterized by the translocation of chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) have markedly improved CML outcomes. Yet, resistance may develop due to mutations in the BCR-ABL kinase domain, particularly in the ATP-binding loop (P-loop), activation loop (A-loop), catalytic domain, and direct binding site. This study aimed to evaluate the relationship between BCR-ABL kinase domain mutations, hematological response, and overall survival among CML patients receiving TKI therapy at Wahidin Sudirohusodo General Hospital, Makassar.</p><p><strong>Methods: </strong>A prospective cohort study was conducted from March 2022 to July 2023 at the Hematology-Oncology outpatient clinic. Among 312 patients, 22 were classified as non-responders (no hematological response within three months) and 290 as responders. Forty-four patients (22 responders and 22 non-responders) underwent mutation analysis, and survival outcomes were compared. Statistical analysis was performed using SPSS.</p><p><strong>Results: </strong>Of the 44 patients, 11 harbored BCR-ABL mutations: S348L (n=6), T315I (n=4), and Y253F (n=1). All mutations were identified exclusively in the non-responder group. Mortality was significantly higher in non-responders than responders (p<0.05), and among non-responders with mutations compared to those without (p<0.01). Six-month survival rates were 65% for S348L, 50% for T315I, and 0% for Y253F, though survival differences between mutation types were not statistically significant (p=0,641).</p><p><strong>Conclusion: </strong>CML patients achieving early hematological response to TKI therapy had significantly better survival outcomes. In contrast, non-responders, particularly those harboring BCR-ABL kinase domain mutations, demonstrated poorer survival. The S348L mutation was the most common variant in this cohort. Early mutation detection may help guide therapeutic adjustments and improve outcomes in TKI-resistant CML.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"27 2","pages":"715-722"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Relationship between SALL4 and Fascin Expression and the Progression of Colorectal Carcinoma. SALL4和fasin表达与大肠癌进展的关系
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.637
Aya M El-Iraqi, Nagwa M Abdel-Rhaman, Azza Kamal Taha

Objective: SALL4 (Spalt-like transcription factor 4) is a stem cell transcription factor that is reactivated in various tumor tissues and has a proven pro-metastatic role in colorectal cancer (CRC). However, the mechanism of its reactivation in CRC remains elusive. fascin is an actin-bundling protein linked to CRC progression. Independent of this activity, fascin regulates stemness and embryonic stem cell-related genes in some cancers. Data on the role of fascin in regulating stem cell transcription factors in CRC are scarce, and the relationship between fascin and SALL4 expression in CRC has not been investigated. This study aims to evaluate the immunohistochemical expression of SALL4 and fascin in fifty-four CRC cases and their relationship with clinicopathological parameters.

Methods: The expression of SALL4 and Fascin determined using immunohistochemistry in 54 paraffin-embedded colectomy specimens from patients with primary colorectal adenocarcinoma.

Result: SALL4-positive expression was detected in 9 cases (16.7%), while moderate-to-high fascin expression was found in 21 cases (38.9%). A significant positive relationship was identified between SALL4 expression and lymphovascular invasion (LVI) (P = 0.033). Moderate-to-high fascin expression was significantly associated with advanced pathological tumor (pT) stage (P = 0.023), lymph node (LN) spread (P = 0.031), and LVI (P = 0.010). Furthermore, a significant association was observed between SALL4 positivity and moderate-to-high fascin expression (P = 0.009).

Conclusion: This is the first study to demonstrate a significant association between SALL4 and fascin expression in CRC patients, suggesting a potential interplay between them. Both proteins may represent potential markers of CRC progression. Molecular studies are required to further investigate the interaction between SALL4 and fascin in CRC.

目的:SALL4 (Spalt-like transcription factor 4)是一种在多种肿瘤组织中被再激活的干细胞转录因子,在结直肠癌(CRC)中具有促转移作用。然而,其在CRC中的再激活机制尚不清楚。束蛋白是一种与结直肠癌进展相关的肌动蛋白捆绑蛋白。独立于这种活性,筋膜蛋白调节一些癌症的干细胞和胚胎干细胞相关基因。关于fasin在CRC中调控干细胞转录因子的作用的数据很少,并且尚未研究fasin与SALL4在CRC中的表达之间的关系。本研究旨在评价54例结直肠癌患者中SALL4和fascin的免疫组织化学表达及其与临床病理参数的关系。方法:应用免疫组织化学方法检测54例原发性结直肠癌结肠腺癌石蜡包埋标本中SALL4和fasin的表达。结果:sall4阳性表达9例(16.7%),中高表达21例(38.9%)。SALL4表达与淋巴血管侵袭(LVI)呈显著正相关(P = 0.033)。中高表达与病理肿瘤晚期(pT)分期(P = 0.023)、淋巴结(LN)扩散(P = 0.031)、LVI (P = 0.010)相关。此外,SALL4阳性与中高筋膜蛋白表达显著相关(P = 0.009)。结论:本研究首次证实了SALL4与结直肠癌患者中fascin表达之间的显著关联,提示两者之间可能存在相互作用。这两种蛋白可能代表结直肠癌进展的潜在标志物。在结直肠癌中,SALL4与束状蛋白的相互作用有待进一步的分子研究。
{"title":"The Relationship between SALL4 and Fascin Expression and the Progression of Colorectal Carcinoma.","authors":"Aya M El-Iraqi, Nagwa M Abdel-Rhaman, Azza Kamal Taha","doi":"10.31557/APJCP.2026.27.2.637","DOIUrl":"https://doi.org/10.31557/APJCP.2026.27.2.637","url":null,"abstract":"<p><strong>Objective: </strong>SALL4 (Spalt-like transcription factor 4) is a stem cell transcription factor that is reactivated in various tumor tissues and has a proven pro-metastatic role in colorectal cancer (CRC). However, the mechanism of its reactivation in CRC remains elusive. fascin is an actin-bundling protein linked to CRC progression. Independent of this activity, fascin regulates stemness and embryonic stem cell-related genes in some cancers. Data on the role of fascin in regulating stem cell transcription factors in CRC are scarce, and the relationship between fascin and SALL4 expression in CRC has not been investigated. This study aims to evaluate the immunohistochemical expression of SALL4 and fascin in fifty-four CRC cases and their relationship with clinicopathological parameters.</p><p><strong>Methods: </strong>The expression of SALL4 and Fascin determined using immunohistochemistry in 54 paraffin-embedded colectomy specimens from patients with primary colorectal adenocarcinoma.</p><p><strong>Result: </strong>SALL4-positive expression was detected in 9 cases (16.7%), while moderate-to-high fascin expression was found in 21 cases (38.9%). A significant positive relationship was identified between SALL4 expression and lymphovascular invasion (LVI) (P = 0.033). Moderate-to-high fascin expression was significantly associated with advanced pathological tumor (pT) stage (P = 0.023), lymph node (LN) spread (P = 0.031), and LVI (P = 0.010). Furthermore, a significant association was observed between SALL4 positivity and moderate-to-high fascin expression (P = 0.009).</p><p><strong>Conclusion: </strong>This is the first study to demonstrate a significant association between SALL4 and fascin expression in CRC patients, suggesting a potential interplay between them. Both proteins may represent potential markers of CRC progression. Molecular studies are required to further investigate the interaction between SALL4 and fascin in CRC.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"27 2","pages":"637-642"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigation of the Anticancer Effects and Senescence Induction of Hesperetin Combined with Cisplatin in Hepatocellular Carcinoma and Embryonic Fibroblast Cell Lines. 橙皮素联合顺铂对肝癌和胚胎成纤维细胞的抗肿瘤作用及诱导衰老的研究。
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.557
Anif Nur Artanti, Riris Istighfari Jenie, Rumiyati Rumiyati, Adam Hermawan, Kato Jun-Ya, Mila Hanifa

Objective: Hepatocellular carcinoma (HCC), the most common form of liver cancer, often develops in individuals with chronic liver diseases, especially cirrhosis. Cisplatin (Cisp), a chemotherapy agent commonly used in HCC treatment, is effective but is known to damage normal cells, including fibroblasts. Hesperetin (HST), a citrus flavanone found abundantly in citrus fruits, has demonstrated antioxidant, anti-inflammatory, and anticancer properties. This study aimed to investigate the synergistic cytotoxic effects and selective induction of senescence by HST in combination with Cisp in HepG2 cancer cells and NIH-3T3 fibroblast cells.

Methods: The cytotoxic effects of HST were assessed using the MTT assay to determine cell viability. The antiproliferative properties were evaluated using colony formation assays. Senescence was assessed using SA-β-gal staining, while flow cytometry was used to analyze cell cycle distribution and apoptosis. Protein expression related to proliferation and apoptosis was determined via Western blot analysis.

Results: MTT assay results indicated that both HST and Cisp reduced HepG2 cell viability in a dose-dependent manner, with IC50 values of 258 ± 2.47 µM and 5 ± 1.83 µM, respectively. Their combination (HST: 33-130 µM; Cisp: 0.6-2.5 µM) showed synergistic effects (combination index, CI < 1) co-treatment with HST (65 and 130 µM) significantly enhanced senescence in HepG2 cells. Clonogenic assays showed inhibition of colony formation, supported by reduced expression of p-ERK1/2 and Cyclin D1. Flow cytometry revealed increased apoptosis and G2/M phase arrest, with upregulation of Bax and caspase-3, and downregulation of Bcl-xL. In NIH-3T3 cells, HST showed minimal cytotoxicity (IC50 > 500 µM), and co-treatment with Cisp reduced senescence markers.

Conclusion: These results suggest that HST and Cisp co-treatment synergistically reduces cancer cell viability while protecting normal fibroblasts from senescence, supporting its potential as a co-chemotherapeutic agent in HCC treatment, while also serving as a protective agent against senescence in healthy tissues.

目的:肝细胞癌(HCC)是最常见的肝癌形式,常发生于慢性肝病患者,尤其是肝硬化患者。顺铂(Cisp),一种常用于HCC治疗的化疗药物,是有效的,但已知会损害正常细胞,包括成纤维细胞。橙皮素(HST)是一种富含柑橘类水果的黄酮,具有抗氧化、抗炎和抗癌的特性。本研究旨在探讨HST联合Cisp对HepG2癌细胞和NIH-3T3成纤维细胞的协同细胞毒作用和选择性诱导衰老作用。方法:采用MTT法测定HST的细胞毒作用。利用菌落形成试验评估其抗增殖特性。采用SA-β-gal染色法观察衰老情况,流式细胞术观察细胞周期分布和凋亡情况。Western blot检测细胞增殖和凋亡相关蛋白的表达。结果:MTT实验结果显示,HST和Cisp均能显著降低HepG2细胞活力,其IC50值分别为258±2.47µM和5±1.83µM。其联合(HST: 33 ~ 130µM; Cisp: 0.6 ~ 2.5µM)具有协同作用(联合指数,CI < 1),与HST(65、130µM)联合处理可显著促进HepG2细胞衰老。克隆实验显示,通过降低p-ERK1/2和Cyclin D1的表达,可以抑制集落的形成。流式细胞术显示凋亡增加,G2/M期阻滞,Bax和caspase-3上调,Bcl-xL下调。在NIH-3T3细胞中,HST表现出最小的细胞毒性(IC50 ~ 500µM),与Cisp共处理可减少衰老标志物。结论:这些结果表明,HST和Cisp共同治疗可协同降低癌细胞活力,同时保护正常成纤维细胞免于衰老,支持其作为HCC治疗的联合化疗药物的潜力,同时也可作为健康组织抗衰老的保护剂。
{"title":"Investigation of the Anticancer Effects and Senescence Induction of Hesperetin Combined with Cisplatin in Hepatocellular Carcinoma and Embryonic Fibroblast Cell Lines.","authors":"Anif Nur Artanti, Riris Istighfari Jenie, Rumiyati Rumiyati, Adam Hermawan, Kato Jun-Ya, Mila Hanifa","doi":"10.31557/APJCP.2026.27.2.557","DOIUrl":"https://doi.org/10.31557/APJCP.2026.27.2.557","url":null,"abstract":"<p><strong>Objective: </strong>Hepatocellular carcinoma (HCC), the most common form of liver cancer, often develops in individuals with chronic liver diseases, especially cirrhosis. Cisplatin (Cisp), a chemotherapy agent commonly used in HCC treatment, is effective but is known to damage normal cells, including fibroblasts. Hesperetin (HST), a citrus flavanone found abundantly in citrus fruits, has demonstrated antioxidant, anti-inflammatory, and anticancer properties. This study aimed to investigate the synergistic cytotoxic effects and selective induction of senescence by HST in combination with Cisp in HepG2 cancer cells and NIH-3T3 fibroblast cells.</p><p><strong>Methods: </strong>The cytotoxic effects of HST were assessed using the MTT assay to determine cell viability. The antiproliferative properties were evaluated using colony formation assays. Senescence was assessed using SA-β-gal staining, while flow cytometry was used to analyze cell cycle distribution and apoptosis. Protein expression related to proliferation and apoptosis was determined via Western blot analysis.</p><p><strong>Results: </strong>MTT assay results indicated that both HST and Cisp reduced HepG2 cell viability in a dose-dependent manner, with IC<sub>50</sub> values of 258 ± 2.47 µM and 5 ± 1.83 µM, respectively. Their combination (HST: 33-130 µM; Cisp: 0.6-2.5 µM) showed synergistic effects (combination index, CI < 1) co-treatment with HST (65 and 130 µM) significantly enhanced senescence in HepG2 cells. Clonogenic assays showed inhibition of colony formation, supported by reduced expression of p-ERK1/2 and Cyclin D1. Flow cytometry revealed increased apoptosis and G2/M phase arrest, with upregulation of Bax and caspase-3, and downregulation of Bcl-xL. In NIH-3T3 cells, HST showed minimal cytotoxicity (IC50 > 500 µM), and co-treatment with Cisp reduced senescence markers.</p><p><strong>Conclusion: </strong>These results suggest that HST and Cisp co-treatment synergistically reduces cancer cell viability while protecting normal fibroblasts from senescence, supporting its potential as a co-chemotherapeutic agent in HCC treatment, while also serving as a protective agent against senescence in healthy tissues.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"27 2","pages":"557-568"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TMEPAI Confers Paclitaxel Resistance in Triple-Negative Breast Cancer Cells by Promoting AKT Phosphorylation and Its Downstream Cascade. TMEPAI通过促进AKT磷酸化及其下游级联作用在三阴性乳腺癌细胞中赋予紫杉醇耐药
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.547
Melva Louisa, Bantari Wisynu Kusuma Wardhani, Yukihide Watanabe, Mitsuyasu Kato

Objective: TMEPAI (transmembrane prostate androgen-induced protein) is one of the proteins associated with the resistance of triple-negative breast cancer (TNBC) to various cytotoxic medicines. However, it has remained uncertain how TMEPAI mechanistically contributes to TNBC resistance to paclitaxel. Thus, this study aimed to investigate the effect and possible mechanism of TMEPAI gene editing via CRISPR-Cas9 on the response of triple-negative breast cancer cells to paclitaxel.

Methods: The present study was conducted on wild-type triple-negative breast cancer cells (BT-549) and BT-549 cells with TMEPAI knocked out using CRISPR-Cas9. Both cell types underwent treatment with TGF-β, followed by paclitaxel, and were evaluated for cell viability and the expression of cell proliferation, apoptosis, drug efflux transporters, and epithelial-mesenchymal transition markers.

Result: TMEPAI knock-out cells exhibited a markedly increased susceptibility to paclitaxel, as characterized by decreased viability and elevated expression of pro-apoptotic genes (Bax, caspase-3, caspase-9), as well as a reduction in anti-apoptotic markers (Bcl-2). The presence of TMEPAI perpetuated the phosphorylation of AKT (pAKT/AKT), elevated the expression of drug efflux transporters (particularly P-glycoprotein and MRP-1), and facilitated epithelial-mesenchymal transition (EMT), as evidenced by increased levels of Snail, Zeb1, and Twist. All these effects were diminished in TMEPAI-knock-out triple-negative breast cancer cells.

Conclusion: TMEPAI appears to facilitate paclitaxel resistance in triple-negative breast cancer cells by promoting cell survival signaling, inhibiting apoptosis, enhancing drug efflux, and initiating epithelial-mesenchymal transition (EMT). Targeting TMEPAI may be a viable approach to overcoming resistance and improving treatment outcomes in triple-negative breast cancer cells.

目的:TMEPAI(跨膜前列腺雄激素诱导蛋白)是三阴性乳腺癌(TNBC)对多种细胞毒性药物耐药的相关蛋白之一。然而,TMEPAI如何在机制上促进TNBC对紫杉醇的耐药性仍不确定。因此,本研究旨在探讨通过CRISPR-Cas9编辑TMEPAI基因对三阴性乳腺癌细胞对紫杉醇反应的影响及其可能机制。方法:采用CRISPR-Cas9对野生型三阴性乳腺癌细胞(BT-549)和TMEPAI敲除的BT-549细胞进行研究。两种细胞分别用TGF-β和紫杉醇处理,并评估细胞活力、细胞增殖、细胞凋亡、药物外排转运蛋白和上皮-间质转化标志物的表达。结果:TMEPAI敲除细胞对紫杉醇的易感性明显增加,表现为活力降低、促凋亡基因(Bax、caspase-3、caspase-9)表达升高,以及抗凋亡标志物(Bcl-2)表达降低。TMEPAI的存在延续了AKT (pAKT/AKT)的磷酸化,提高了药物外排转运蛋白(特别是p -糖蛋白和MRP-1)的表达,并促进了上皮-间质转化(EMT),如Snail, Zeb1和Twist水平的增加。在tmepai敲除的三阴性乳腺癌细胞中,所有这些影响都减弱了。结论:TMEPAI可能通过促进细胞存活信号、抑制细胞凋亡、增强药物外排和启动上皮-间质转化(EMT)来促进三阴性乳腺癌细胞的紫杉醇耐药。靶向TMEPAI可能是克服耐药和改善三阴性乳腺癌细胞治疗结果的可行方法。
{"title":"TMEPAI Confers Paclitaxel Resistance in Triple-Negative Breast Cancer Cells by Promoting AKT Phosphorylation and Its Downstream Cascade.","authors":"Melva Louisa, Bantari Wisynu Kusuma Wardhani, Yukihide Watanabe, Mitsuyasu Kato","doi":"10.31557/APJCP.2026.27.2.547","DOIUrl":"https://doi.org/10.31557/APJCP.2026.27.2.547","url":null,"abstract":"<p><strong>Objective: </strong>TMEPAI (transmembrane prostate androgen-induced protein) is one of the proteins associated with the resistance of triple-negative breast cancer (TNBC) to various cytotoxic medicines. However, it has remained uncertain how TMEPAI mechanistically contributes to TNBC resistance to paclitaxel. Thus, this study aimed to investigate the effect and possible mechanism of TMEPAI gene editing via CRISPR-Cas9 on the response of triple-negative breast cancer cells to paclitaxel.</p><p><strong>Methods: </strong>The present study was conducted on wild-type triple-negative breast cancer cells (BT-549) and BT-549 cells with TMEPAI knocked out using CRISPR-Cas9. Both cell types underwent treatment with TGF-β, followed by paclitaxel, and were evaluated for cell viability and the expression of cell proliferation, apoptosis, drug efflux transporters, and epithelial-mesenchymal transition markers.</p><p><strong>Result: </strong>TMEPAI knock-out cells exhibited a markedly increased susceptibility to paclitaxel, as characterized by decreased viability and elevated expression of pro-apoptotic genes (Bax, caspase-3, caspase-9), as well as a reduction in anti-apoptotic markers (Bcl-2). The presence of TMEPAI perpetuated the phosphorylation of AKT (pAKT/AKT), elevated the expression of drug efflux transporters (particularly P-glycoprotein and MRP-1), and facilitated epithelial-mesenchymal transition (EMT), as evidenced by increased levels of Snail, Zeb1, and Twist. All these effects were diminished in TMEPAI-knock-out triple-negative breast cancer cells.</p><p><strong>Conclusion: </strong>TMEPAI appears to facilitate paclitaxel resistance in triple-negative breast cancer cells by promoting cell survival signaling, inhibiting apoptosis, enhancing drug efflux, and initiating epithelial-mesenchymal transition (EMT). Targeting TMEPAI may be a viable approach to overcoming resistance and improving treatment outcomes in triple-negative breast cancer cells.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"27 2","pages":"547-555"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevalence of Transcriptionally Active HPV16 and HPV18 infection in Anogenital Warts: A Study in Sikkim, India. 转录活性HPV16和HPV18感染在肛门生殖器疣的患病率:在印度锡金的一项研究。
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.659
Sunaina Lal, Rukma Lal Sharma, Anup Pradhan, Mingma Lhamu Sherpa

Background: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection globally and is causally related to anogenital and oral cancers, with 311,000 associated deaths recorded in men and women every year. The presence of oncogenic HPV genotypes in anogenital warts is reported by few studies, while many groups have reported an associated higher risk of anogenital and other cancers in patients with anogenital warts. This study aimed to detect HPV16 and HPV18 DNA and mRNA markers in anogenital warts to assess infection and viral persistence.

Method: A cross-sectional study design was adopted to enroll 50 consenting men and women presenting with anogenital warts at the dermatology clinics of two existing referral hospitals in Sikkim. Samples were processed for DNA and RNA extraction, cDNA conversion, followed by qPCR-based amplification for HPV16 and HPV18 E6/E7 DNA and mRNA.

Result: High presence of E6/E7 genes of HPV16 and HPV18 with DNA and mRNA was observed in the exfoliated anogenital warts tissue samples, evaluated using quantitative PCR (qPCR). HPV16E6 and HPV18E6 DNA was present in 75.5% (37/49) and 26.6% (13/49) of the samples, while HPV16E6 and HPV18E6 mRNA was present in 62.0% (31/50) and 52.0% (26/50) of the samples, respectively, 18.0% (9/50) of the samples tested positive for HPV16E7 mRNA, while none were positive for HPV18E7 mRNA.

Conclusion: High prevalence of HPV16 and HPV18 seen in males and females with Anogenital warts in the present study re-emphasizes the significance of including men in HPV screening and vaccination programs, and importance of testing oncogenic HPV genotypes in anogenital warts to improve the overall reduction of clinical manifestations associated with HPV.

背景:人乳头瘤病毒(HPV)是全球最普遍的性传播感染,与肛门生殖器癌和口腔癌有因果关系,每年有31.1万男性和女性死亡。很少有研究报告在肛门生殖器疣中存在致癌的HPV基因型,而许多研究小组报告了肛门生殖器疣患者患肛门生殖器和其他癌症的相关风险较高。本研究旨在检测肛门生殖器疣中HPV16和HPV18的DNA和mRNA标记物,以评估感染和病毒持久性。方法:采用横断面研究设计,在锡金两家现有转诊医院的皮肤科诊所招募50名同意患有肛门生殖器疣的男性和女性。对样品进行DNA和RNA提取、cDNA转化、HPV16和HPV18 E6/E7 DNA和mRNA的qpcr扩增。结果:HPV16和HPV18的E6/E7基因以DNA和mRNA的形式存在于脱落的生殖器疣组织样本中,采用定量PCR (qPCR)进行鉴定。HPV16E6和HPV18E6的DNA阳性率分别为75.5%(37/49)和26.6% (13/49),HPV16E6和HPV18E6的mRNA阳性率分别为62.0%(31/50)和52.0% (26/50),HPV16E7 mRNA阳性率分别为18.0% (9/50),HPV18E7 mRNA阳性率均为零。结论:本研究在男性和女性肛门生殖器疣患者中发现HPV16和HPV18的高患病率,再次强调了将男性纳入HPV筛查和疫苗接种计划的重要性,以及在肛门生殖器疣中检测致癌HPV基因型对改善总体减少与HPV相关的临床表现的重要性。
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引用次数: 0
Ambient Air Pollution and Risk of Brain Tumors: A Systematic Review and Meta-Analysis. 环境空气污染与脑肿瘤风险:一项系统综述和荟萃分析。
Q2 Medicine Pub Date : 2026-02-01 DOI: 10.31557/APJCP.2026.27.2.423
Ali Fadhil Hashim, Amirreza Karimi, Sanaz Ghanbari, Azizova Feruza, Nawras Abdel Abbas Esmaeel, Hussain Ali Rzoqy, Mozhgan Taebi, Soheyla Kalantari, Samad Karkhah, Azadeh Emami, Reza Salehi

Background: The potential link between ambient air pollution and brain tumor incidence remains poorly understood, despite growing concern about environmental exposures and neurological health. While air pollutants are established carcinogens for several cancer types, their role in central nervous system (CNS) tumorigenesis has not been definitively established.

Aim: This study aims to systematically evaluate and quantitatively synthesize the epidemiological evidence on the association between long-term exposure to ambient air pollution and the risk of brain tumors, including gliomas and meningiomas.

Methods: A comprehensive literature search was conducted across PubMed, Embase, Scopus, Web of Science, and ProQuest (up to October 1, 2024), identifying observational studies assessing associations between air pollution and brain tumor incidence. Eligible studies were screened, data were extracted, and study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed to estimate pooled relative risks (RR) for specific pollutants (PM2.5, NOx, NO2), and traffic proximity. Subgroup analyses and publication bias assessments were also conducted.

Results: Eight studies met inclusion criteria, with five contributing to the meta-analysis. Pooled estimates indicated an association between long-term exposure to NO2 and brain tumors (RR = 1.06; 95% CI: 1.01-1.11). PM2.5 exposure showed a higher but more variable association (RR = 1.63; 95% CI: 1.04-2.55), while NOx (RR = 1.16; 95% CI: 0.93-1.45) and traffic proximity (RR = 1.07; 95% CI: 0.99-1.16) demonstrated weaker or borderline associations. Subgroup analyses suggested slightly stronger associations for meningioma than glioma. Significant heterogeneity was observed across studies, but no clear evidence of publication bias was detected.

Conclusions: This systematic review and meta-analysis provides suggestive evidence that long-term exposure to traffic-related air pollutants may be associated with a modestly increased risk of brain tumors. While results are not conclusive, the widespread exposure to these pollutants and the observed trends underscore the importance of further research using refined exposure assessments and tumor subtype-specific analyses.

背景:尽管人们越来越关注环境暴露和神经系统健康,但环境空气污染与脑肿瘤发病率之间的潜在联系仍然知之甚少。虽然空气污染物已被确定为几种癌症类型的致癌物,但它们在中枢神经系统(CNS)肿瘤发生中的作用尚未得到明确确定。目的:本研究旨在系统评价和定量综合长期暴露于环境空气污染与脑肿瘤(包括胶质瘤和脑膜瘤)发病风险相关性的流行病学证据。方法:通过PubMed、Embase、Scopus、Web of Science和ProQuest(截止到2024年10月1日)进行综合文献检索,确定评估空气污染与脑肿瘤发病率之间关系的观察性研究。筛选符合条件的研究,提取数据,并使用纽卡斯尔-渥太华量表评估研究质量。进行随机效应荟萃分析,以估计特定污染物(PM2.5、NOx、NO2)和交通距离的总相对风险(RR)。还进行了亚组分析和发表偏倚评估。结果:8项研究符合纳入标准,其中5项对meta分析有贡献。综合估计表明长期暴露于二氧化氮与脑肿瘤之间存在关联(RR = 1.06; 95% CI: 1.01-1.11)。PM2.5暴露表现出更高但更可变的相关性(RR = 1.63; 95% CI: 1.04-2.55),而氮氧化物(RR = 1.16; 95% CI: 0.93-1.45)和交通邻近(RR = 1.07; 95% CI: 0.99-1.16)表现出较弱或边缘相关性。亚组分析显示脑膜瘤与神经胶质瘤的相关性略强。各研究均观察到显著的异质性,但未发现明显的发表偏倚证据。结论:本系统综述和荟萃分析提供了启发性证据,表明长期暴露于交通相关的空气污染物可能与脑肿瘤风险适度增加有关。虽然结果不是结论性的,但这些污染物的广泛暴露和观察到的趋势强调了使用精确暴露评估和肿瘤亚型特异性分析进行进一步研究的重要性。
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引用次数: 0
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Asian Pacific Journal of Cancer Prevention
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