{"title":"A new model based on preoperative AFP, albumin, and tumor burden score for predicting microvascular invasion in early-stage HCC.","authors":"Yuan-Sheng Chang, Mu-Jung Tsai, Chieh-Jui Tsai, Chih-Chi Wang, Chih-Che Lin, Yi-Hao Yen, Chao-Hung Hung, Yuan-Hung Kuo, Ding-Sen Huang, Wei-Chen Tai, Tsung-Hui Hu, Ming-Chao Tsai","doi":"10.62347/ZGRJ7827","DOIUrl":"10.62347/ZGRJ7827","url":null,"abstract":"<p><p>Microscopic vascular invasion (MVI) has been demonstrated as a strong risk factor associated with tumor recurrence and poor overall survival among hepatocellular carcinoma (HCC) patients after resection, but the preoperative prediction of MVI is still challenging. We aimed to build and validate a novel model to predict MVI in the preoperative setting. We retrospectively collected 857 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection at Kaohsiung Chang Gung Hospital between January 2001 and June 2016. The patients were randomized into derivation (n = 648) and validation groups (n = 209). Logistic regression analysis was used to screen out independent risk factors for MVI and further constructed a predictive model for MVI. Prediction performance was compared by the area under the receiver operating characteristic curve (AUC). The multivariable logistic regression analysis of the training cohort found that alpha-fetoprotein (AFP) ≥ 20 ng/mL (OR = 1.96, 95% CI: 1.41-2.73, P < 0.001), albumin < 3.5 g/dL (OR = 1.48, 95% CI: 1.06-2.05, P = 0.019) and tumor burden score (TBS) ≥ 8.6 (OR = 2.54, 95% CI: 1.49-4.35, P = 0.001) to be independent risk factors for MVI. The three factors were chosen to build a model for prediction of MVI. The AUC for the training and validation group was 0.619 (95% CI: 0.575-0.663) and 0.642 (95% CI: 0.562-0.722), respectively, and the calibration plot showed good performance of the prediction model, with a low mean absolute error at 0.01. In conclusion, the new model comprised AFP, albumin, and TBS that can predict risk of MVI for early-stage HCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4979-4988"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A patient-derived xenograft mouse platform from epithelioid glioblastoma provides possible druggable screening and translational study.","authors":"Chiao-Yun Lin, Chen-Yang Huang, Cheng-Chi Lee, Lien-Min Li, Ya-Fang Lee, Shi-Ming Jung, Hsien-Chi Fan, An-Chi Lin, Cheng-Lung Hsu, Yin-Cheng Huang","doi":"10.62347/LQIJ5334","DOIUrl":"10.62347/LQIJ5334","url":null,"abstract":"<p><p>Despite advancements in targeted therapy, glioblastoma remains a challenging condition with limited treatment options. While surgical techniques and external radiation therapy have improved, the median survival for glioblastoma stands at around 12-18 months, with a 5-year survival rate of only 6.8%. Epithelioid glioblastoma (eGBM) represents a rare subtype within the glioma spectrum. Utilizing patient-derived xenograft (PDX) models in mice offers a promising avenue for drug screening and translational research, particularly for this specific glioblastoma subtype. Establishing a stable PDX model for eGBM revealed consistent genetic abnormalities, including <i>BRAF V600E</i> mutation and <i>CDKN2A</i> deletion, in both primary and PDX tumors. Leveraging a curated drug database, compounds potentially targeting these aberrations were identified. By using the novel PDX platform, the results presented in this study demonstrate that the treatments with Palbociclib or Dabrafenib/Trametinib significantly reduced tumor size. RNA sequencing analysis further validated the responsiveness of the tumors to these targeted therapies. In conclusion, PDX models offer a deeper understanding of eGBM at the genomic level and facilitate the identification of potential therapeutic targets. Further translational studies of this novel PDX model hold promise for advancing the diagnosis and treatment of this specific subtype of glioblastoma.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4747-4759"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lexie Kessler, Chail Koo, Claus-Peter Richter, Xiaodong Tan
{"title":"Hearing loss during chemotherapy: prevalence, mechanisms, and protection.","authors":"Lexie Kessler, Chail Koo, Claus-Peter Richter, Xiaodong Tan","doi":"10.62347/OKGQ4382","DOIUrl":"https://doi.org/10.62347/OKGQ4382","url":null,"abstract":"<p><p>Ototoxicity is an often-underestimated sequela for cancer patients undergoing chemotherapy, with an incidence rate exceeding 50%, affecting approximately 4 million individuals worldwide each year. Despite the nearly 2,000 publications on chemotherapy-related ototoxicity in the past decade, the understanding of its prevalence, mechanisms, and preventative or therapeutic measures remains ambiguous and subject to debate. To date, only one drug, sodium thiosulfate, has gained FDA approval for treating ototoxicity in chemotherapy. However, its utilization is restricted. This review aims to offer clinicians and researchers a comprehensive perspective by thoroughly and carefully reviewing available data and current evidence. Chemotherapy-induced ototoxicity is characterized by four primary symptoms: hearing loss, tinnitus, vertigo, and dizziness, originating from both auditory and vestibular systems. Hearing loss is the predominant symptom. Amongst over 700 chemotherapeutic agents documented in various databases, only seven are reported to induce hearing loss. While the molecular mechanisms of the hearing loss caused by the two platinum-based drugs are extensively explored, the pathways behind the action of the other five drugs are primarily speculative, rooted in their therapeutic properties and side effects. Cisplatin attracts the majority of attention among these drugs, encompassing around two-thirds of the literature regarding ototoxicity in chemotherapy. Cisplatin ototoxicity chiefly manifests through the loss of outer hair cells, possibly resulting from damages directly by cisplatin uptake or secondary effects on the stria vascularis. Both direct and indirect influences contribute to cisplatin ototoxicity, while it is still debated which path is dominant or where the primary target of cisplatin is located. Candidates for hearing protection against cisplatin ototoxicity are also discussed, with novel strategies and methods showing promise on the horizon.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4597-4632"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular significance of circRNAs in malignant lymphoproliferative disorders: pathogenesis and novel biomarkers or therapeutic targets.","authors":"Bo-Yang Long, Yan Wang, Shu-Hong Hao, Guang Shi","doi":"10.62347/KMWB5164","DOIUrl":"https://doi.org/10.62347/KMWB5164","url":null,"abstract":"<p><p>Recent studies have shown that circular RNAs (CircRNAs) have the novel functions and molecular mechanisms in the pathogenesis of malignant diseases. CircRNAs have been found to be associated with the occurrence and development of lymphoproliferative diseases, impacting on lymphocyte proliferation. This article provides a review of the pathogenesis of circRNAs in malignant lymphoproliferative disorders, focusing on conditions such as acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and lymphoma. Additionally, it discusses the potential value of circRNAs as novel biomarkers or therapeutic targets in these disorders.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4633-4651"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ZIP4: a promising early diagnostic and therapeutic targets for pancreatic cancer.","authors":"Yunpeng Tang, Sheng Guo, Nianhui Yu, Hui Li","doi":"10.62347/AVYM3477","DOIUrl":"https://doi.org/10.62347/AVYM3477","url":null,"abstract":"<p><p>Pancreatic cancer is an aggressive and metastatic tumor that lacks effective early detection and treatment methods. There is an urgent need to further understand its underlying molecular mechanisms and identify new biomarkers for early detection. Zinc, a critical trace element and catalytic cofactor, is tightly regulated within cells. ZIP4, a zinc transporter protein significantly overexpressed in human pancreatic cancer, appears to play a pivotal role in tumor development by modulating intracellular zinc concentration. This review highlights the role of ZIP4 in tumorigenesis, including its impact on pancreatic cancer growth, proliferation, migration, and drug resistance. ZIP4 exerts its effects by regulating zinc dependent transcriptional factors like CREB, STAT3, and ZEB1, resulting in upregulation of Cyclin D1, TP53INP1, ITGA3, CD44, ENT1 proteins, and miR-373. Moreover, ZIP4 mediates the miR373-PHLPP2-AKT signaling axis, which increases TGF-β expression. Coupled with CREB-activated macrophage catabolism-related genes SDC1 and DNM2, ZIP4 promotes cancer cachexia and supports amino acids to tumor cells under metabolic stress. Furthermore, ZIP4 facilitates bone resorption by osteoclasts via the RANKL-activated NF-κB pathway. A deeper understanding of these mechanisms may unveil potential targets for early diagnosis, prognosis assessment, and dietary recommendations for pancreatic cancer. These findings hold clinical significance not only for pancreatic cancer but also for other malignancies exhibiting heightened ZIP4 expression.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4652-4664"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research progress on machine algorithm prediction of liver cancer prognosis after intervention therapy.","authors":"Feng Guo, Hao Hu, Hao Peng, Jia Liu, Chengbo Tang, Hao Zhang","doi":"10.62347/BEAO1926","DOIUrl":"https://doi.org/10.62347/BEAO1926","url":null,"abstract":"<p><p>The treatment for liver cancer has transitioned from traditional surgical resection to interventional therapies, which have become increasingly popular among patients due to their minimally invasive nature and significant local efficacy. However, with advancements in treatment technologies, accurately assessing patient response and predicting long-term survival has become a crucial research topic. Over the past decade, machine algorithms have made remarkable progress in the medical field, particularly in hepatology and prognosis studies of hepatocellular carcinoma (HCC). Machine algorithms, including deep learning and machine learning, can identify prognostic patterns and trends by analyzing vast amounts of clinical data. Despite significant advancements, several issues remain unresolved in the prognosis prediction of liver cancer using machine algorithms. Key challenges and main controversies include effectively integrating multi-source clinical data to improve prediction accuracy, addressing data privacy and ethical concerns, and enhancing the transparency and interpretability of machine algorithm decision-making processes. This paper aims to systematically review and analyze the current applications and potential of machine algorithms in predicting the prognosis of patients undergoing interventional therapy for liver cancer, providing theoretical and empirical support for future research and clinical practice.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4580-4596"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IDO1-mediated kynurenine production inhibits IGFBP5 signaling to promote 5-fluorouracil-induced senescence escape and chemoresistance in colorectal cancer.","authors":"Yu Li, Chao Li, Xufeng Yao, Junjie Lv, Wenjun Li, Rong Fu, Mengyang Chen, Peng Yang, Qian Dai, Wei Wei, Zongwei Li","doi":"10.62347/XTRC3347","DOIUrl":"https://doi.org/10.62347/XTRC3347","url":null,"abstract":"<p><p>Cellular senescence is an irreversible state of growth arrest, and induction of senescence is considered a potential therapeutic strategy against cancer. Indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme catabolizing L-tryptophan into kynurenine, plays a key role in tumor immune tolerance. However, the roles of IDO1 in cellular senescence and chemoresistance remain elusive. Herein, we observed a significant elevation of IDO1 expression in colorectal cancer (CRC) tissues compared to non-neoplastic controls, based on both the GEPIA database and mouse model. Functionally, ectopic expression of IDO1 blunted 5-fluorouracil (5-FU)-induced cell senescence and rendered CRC cells more refractory towards 5-FU treatment, whereas IDO1 silencing resulted in opposing effects. Further studies demonstrated that IDO1 overexpression decreased the levels of senescent-related proteins, including p16, p21, p53, and cyclin D1. Mechanistically, the kynurenine released from IDO1-expressing CRC cells inhibited the IGFBP5/p53 signaling pathway, accounting for IDO1-mediated suppression of cell senescence and induction of chemoresistance. Collectively, these data revealed an unrecognized role of IDO1 in senescence escape and chemoresistance via releasing its catabolite kynurenine, implicating that therapeutically targeting IDO1 or IGFBP5/p53 signaling pathway holds great promise for CRC treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4551-4566"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-Sheng Xu, Yu-Shui Ma, Rong-Hua Dai, Huan-Le Zhang, Qin-Xin Yang, Qi-Yu Fan, Xin-Yun Liu, Ji-Bin Liu, Wei-Wei Feng, He Meng, Da Fu, Hong Yu, Jian Shen
{"title":"Identification of novel genomic hotspots and tumor-relevant genes via comprehensive analysis of HPV integration in Chinese patients of cervical cancer.","authors":"Xiao-Sheng Xu, Yu-Shui Ma, Rong-Hua Dai, Huan-Le Zhang, Qin-Xin Yang, Qi-Yu Fan, Xin-Yun Liu, Ji-Bin Liu, Wei-Wei Feng, He Meng, Da Fu, Hong Yu, Jian Shen","doi":"10.62347/KKLE8602","DOIUrl":"https://doi.org/10.62347/KKLE8602","url":null,"abstract":"<p><p>Cervical cancer accounts for 10-15% of cancer-related mortality among women globally. Infection with high-risk human papillomavirus (HPV) types constitutes a significant etiological factor in the development of cervical carcinoma. The integration of HPV DNA into the host genome is considered a pivotal event in cervical carcinogenesis. Nevertheless, the precise mechanisms underlying HPV integration and its role in promoting cancer progression remain inadequately understood. Therefore, this study aims to identify potential common denominators at HPV DNA integration sites and to analyze the adjacent cellular sequences. We conducted whole-genome sequencing on 13 primary cervical cancer samples, employing the chromosomal coordinates of 537 breakpoints to assess the statistical overrepresentation of integration sites in relation to various chromatin features. Our analysis, which encompassed all chromosomes, identified several integration hotspots within the human genome, notably at 14q32.2, 10p15, and 2q37. Additionally, our findings indicated a preferential integration of HPV DNA into intragenic and gene-dense regions of human chromosomes. A substantial number of host cellular genes impacted by the integration sites were associated with cancer, including IKZF2, IL26, AHRR, and PDCD6. Furthermore, the cellular genes targeted by integration were enriched in tumor-related terms and pathways, as demonstrated by gene ontology and KEGG analysis. In conclusion, these findings enhance our understanding of HPV integration sites and provide deeper insights into the molecular mechanisms underlying the pathogenesis of cervical carcinoma.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4665-4682"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of concurrent MASLD on early-stage HCC following curative resection in chronic hepatitis B.","authors":"Cao-Ngoc Huynh, Yu-Chieh Tsai, Mu-Jung Tsai, Chieh-Jui Tsai, Chih-Chi Wang, Chih-Che Lin, Yi-Hao Yen, Chao-Hung Hung, Yuan-Hung Kuo, Wei-Chen Tai, Tsung-Hui Hu, Ming-Chao Tsai","doi":"10.62347/LJRG3048","DOIUrl":"https://doi.org/10.62347/LJRG3048","url":null,"abstract":"<p><p>In 2023, a new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), replaced the term non-alcoholic fatty liver disease (NAFLD). With the global rise in MASLD prevalence, concurrent MASLD and chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) are becoming increasingly common. This study aimed to evaluate the clinical impact of concurrent MASLD on long-term survival outcomes in patients with CHB-related early-stage HCC following curative resection. This retrospective study included patients diagnosed with CHB-related early-stage HCC who underwent curative hepatectomy between January 2010 and December 2019. We examined the association between histologically confirmed MASLD and clinical outcomes, with overall survival (OS) and recurrence-free survival (RFS) calculated using the Kaplan-Meier method and compared using the log-rank test. Of 587 eligible patients, 275 (46.8%) were diagnosed with concurrent MASLD. Patients with concurrent MASLD had a higher prevalence of diabetes, hypertension, body mass index (BMI) > 23 kg/m<sup>2</sup>, a lower proportion of AFP > 200 ng/ml, and microvascular invasion compared to those without MASLD. After a median follow-up of 66 months, patients with concurrent MASLD exhibited a lower risk of death (HR: 0.57, 95% CI: 0.34-0.95, <i>P</i> = 0.030) but no significant difference in HCC recurrence rates. Subgroup analysis revealed significantly higher OS in females, individuals with BMI ≥ 23 kg/m<sup>2</sup>, and non-cirrhotic patients (all <i>P</i> < 0.05). In conclusion, concurrent MASLD is associated with improved survival in patients with CHB-related HCC following curative resection, particularly in females, those with BMI ≥ 23 kg/m<sup>2</sup>, and non-cirrhotic patients.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4567-4579"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}