Cancer Medicine最新文献

{"title":"Pan-Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System","authors":"Sean R. Miller,&nbsp;Matthew Schipper,&nbsp;Lars G. Fritsche,&nbsp;Ralph Jiang,&nbsp;Garth Strohbehn,&nbsp;Erkin Ötleş,&nbsp;Benjamin H. McMahon,&nbsp;Silvia Crivelli,&nbsp;Rafael Zamora-Resendiz,&nbsp;Nithya Ramnath,&nbsp;Shinjae Yoo,&nbsp;Xin Dai,&nbsp;Kamya Sankar,&nbsp;Donna M. Edwards,&nbsp;Steven G. Allen,&nbsp;Michael D. Green,&nbsp;Alex K. Bryant","doi":"10.1002/cam4.70379","DOIUrl":"10.1002/cam4.70379","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cumulative, health system-wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real-world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system-wide survival impact of ICIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified all patients receiving PD-1/PD-L1 or CTLA-4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non-ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer-related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life-years gained system-wide were calculated from the difference in adjusted 5-year restricted mean survival times.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, <i>p</i> &lt; 0.001; urothelial: aHR 0.91, 95% CI 0.83–1.01, <i>p</i> = 0.066). The relative benefit of ICI was stable across patient age, comorbidity, and self-reported race subgroups. Across VHA, 15,859 life-years gained were attributable to ICI within 5-years of treatment, with NSCLC contributing the most life-years gained.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isobutyric Acid Promotes Immune Evasion in Colorectal Cancer via Increased PD-L1 Expression","authors":"Qiuhua Lin,&nbsp;Han Wang,&nbsp;Wenbo Chen,&nbsp;Xinjie Wei,&nbsp;Jinglian Chen,&nbsp;Ying Deng,&nbsp;Chunyin Wei,&nbsp;Hao Lai,&nbsp;Xianwei Mo,&nbsp;Weizhong Tang,&nbsp;Tao Luo","doi":"10.1002/cam4.70397","DOIUrl":"10.1002/cam4.70397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Isobutyric acid (IBA), a short-chain fatty acid, has been unequivocally demonstrated to exert significant influence on the progression of colorectal cancer (CRC). Nevertheless, a comprehensive understanding of its intricate regulatory mechanisms remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing advanced techniques such as western blot, RT-qPCR, and flow cytometry, we systematically investigated the impact of IBA on the expression of PD-L1 in CRC cells. Concurrently, employing RNA silencing technology and small-molecule inhibitors, we delved into the molecular intricacies underlying the regulatory axis of IBA involving ROCK1/c-Myc/PD-L1. Furthermore, through flow cytometry analysis, we examined the alterations in the tumor immune microenvironment following anti-PD-L1 antibody therapy in a murine tumor model treated with IBA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated levels of IBA were found to robustly activate PD-L1 expression in CRC cells both in vitro and in vivo, concomitantly reshaping the tumor immune microenvironment. Subsequent mechanistic investigations unveiled that IBA, through its interaction and activation of ROCK1, promotes the activation of c-Myc, thereby enhancing the transcription of PD-L1. Silencing of ROCK1 and application of ROCK1 inhibitors effectively reversed the regulatory effects of IBA on PD-L1. Additionally, IBA inhibited the activity of infiltrating CD8⁺ T cells, resulting in diminished antitumor immunity and attenuating the sensitivity to anti-PD-L1 therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study elucidates a novel mechanism by which IBA inhibits the sensitivity of CRC to anti-PD-L1 antibody therapy. Emphasizing IBA and its downstream pathways as potential therapeutic targets for immune therapy resistance mechanisms, our findings provide a novel theoretical foundation for overcoming immune therapy resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model","authors":"Koorosh Tabatabaei,&nbsp;Sara Moazzezi,&nbsp;Mohammadreza Emamgholizadeh,&nbsp;Haleh Vaez,&nbsp;Behzad Baradaran,&nbsp;Behrooz Shokouhi","doi":"10.1002/cam4.70395","DOIUrl":"10.1002/cam4.70395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose-depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effects, so we hypothesized that CBD administration with high-dose DOX chemotherapy can improve anticancer activity and reduce cardiotoxic side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Mice breast cancer model established by injecting 4T1 cell lines. One group was not injected by 4T1 cells as a not cancerous group and received normal saline (NS, 0.1 mL). In cancerous groups, first group was considered as cancerous control and received NS (0.1 mL); the second group received CBD (5 mg/kg, IP) on Days 1,7, and 14; in the third group DOX (5 mg/kg, IV) as CBD schedule was administrated; the fourth group treated with CBD 1 day before DOX injection as pretreatment, and the last group was treated with CBD and DOX at same time with previous doses and schedules. On Day 21, all mice were sacrificed, heart and lungs tissues were obtained and histological sections were isolated. SOD2, iNOS, MMP2, MMP9 were evaluated through western blot and TUNEL test preformed for breast tumor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tumor size and weight significantly decreased in DOX, pretreatment CBD + DOX and CBD + DOX groups. Administration of CBD with DOX could not prevent weight loss. TUNEL test demonstrated the highest tumor cell apoptosis in pretreatment CBD + DOX and CBD + DOX. In lungs belonged to CBD + DOX, there was not any sign of metastasis. Cardiac histopathological examination of pretreatment CBD + DOX and CBD + DOX did not show any sign of congestion or inflammation. In CBD + DOX SOD2 increased, also iNOS, MMP2, and MMP9 decreased compared to DOX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune Diseases and Risk of Non-Hodgkin Lymphoma: A Mendelian Randomisation Study","authors":"Xiaoting Shi,&nbsp;Joshua D. Wallach,&nbsp;Xiaomei Ma,&nbsp;Tormod Rogne","doi":"10.1002/cam4.70327","DOIUrl":"10.1002/cam4.70327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-Hodgkin lymphoma (NHL) is one of the most common haematologic malignancies in the world. Despite substantial efforts to identify causes and risk factors for NHL, its aetiology is largely unclear. Autoimmune diseases have long been considered potential risk factors for NHL. We carried out Mendelian randomisation (MR) analyses to examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of NHL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two-sample MR was performed using publicly available summary statistics from cohorts of European ancestry. For NHL and four NHL subtypes, we used data from UK Biobank, Kaiser Permanente cohorts, and FinnGen studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92–0.98, <i>p</i> = 5 × 10⁻³, and OR 0.92, 95% CI: 0.85–0.99, <i>p</i> = 2.8 × 10⁻², respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Exploring the Anticancer Mechanism of Cardiac Glycosides Using Proteome Integral Solubility Alteration Approach”","authors":"","doi":"10.1002/cam4.70381","DOIUrl":"10.1002/cam4.70381","url":null,"abstract":"<p>\u0000 <span>Qin, W</span>, <span>Deng, Y</span>, <span>Ren, H</span>, <span>Liu, Y</span>, <span>Liu, L</span>, <span>Liu, W</span>, <span>Zhao, Y</span>, <span>Li, C</span>, <span>Yang, Z</span>. <span>Exploring the Anticancer Mechanism of Cardiac Glycosides Using Proteome Integral Solubility Alteration Approach</span>. <i>Cancer Medicine</i> <span>2024</span>; <span>13</span>(<span>18</span>):e70252. https://doi.org/10.1002/cam4.70252.\u0000 </p><p>In the first of the affiliations, the text “The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital)” was incorrect. This should have read: “Hunan Provincial People's Hospital, (The First Affiliated Hospital of Hunan Normal University)”.</p><p>We apologize for this error.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of CellCollector Assay to Detect Free Cancer Cells in the Peritoneal Cavity of Colorectal Cancer Patients: An Experimental Study","authors":"Yudi Wu,&nbsp;Fangxun He,&nbsp;Liang Liu,&nbsp;Wei Jiang,&nbsp;Jiao Deng,&nbsp;Yujie Zhang,&nbsp;Zhixin Cao,&nbsp;Xiangshang Xu,&nbsp;Jianping Gong","doi":"10.1002/cam4.70378","DOIUrl":"10.1002/cam4.70378","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) is associated with high incidence and mortality rates globally. The presence of intraperitoneal free cancer cells (IFCCs) is recognized as an independent prognostic factor for CRC patients. However, a clinical gold standard for IFCCs detection is lacking. The GILUPI CellCollector has demonstrated high sensitivity and specificity in detecting free cancer cells, yet its application for CRC IFCCs detection remains unreported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We selected CRC and normal cell lines to evaluate the CellCollector's ability to detect tumor cells. A total of 70 CRC patients and 17 patients with benign disease undergoing laparoscopic procedures were investigated. Peritoneal lavage fluid was collected pre- and post-operation, and both real-time PCR (CEA mRNA) and CellCollector detection were performed. We compared the sensitivity and specificity of these two methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CellCollector can distinguish well between CRC and normal cells in cell line experiments. CellCollector detects IFCCs better than real-time PCR (CEA) in CRC patients in different TNM Stages. The sensitivity of CellCollector was higher than that of real-time PCR (84.6% vs. 48.4%), and the specificity of CellCollector was also higher than real-time PCR (79.1% vs. 60.4%). There was no significant difference in the results of IFCCs detected by CellCollector before and after total mesorectal excision (TME) or complete mesocolic excision (CME) radical colorectomy (<i>p</i> &gt; 0.05), but there was a significant difference in real-time PCR detection (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The CellCollector demonstrates superior sensitivity and specificity compared to real-time PCR for detecting IFCCs in CRC patients, suggesting its potential as a clinical tool for IFCCs detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT01978444</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional Healthcare Access Barriers to Prostate-Specific Antigen Testing: A Nation-Wide Panel Study in the United States From 2006 to 2020","authors":"Hari S. Iyer,&nbsp;Kevin H. Kensler,&nbsp;Charlotte Roscoe,&nbsp;Chidinma Opara,&nbsp;Mingchao He,&nbsp;Evan Kovac,&nbsp;Isla P. Garraway,&nbsp;Quoc Dien-Trinh,&nbsp;Timothy R. Rebbeck","doi":"10.1002/cam4.70358","DOIUrl":"10.1002/cam4.70358","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual-level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey-weighted, covariate-adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (<i>P</i>_het &lt; 0.004 for insurance and regular PCP) and for those with college education compared to those without (<i>P</i>_het &lt; 0.05 for insurance, perceived unaffordability).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial and Ethnic Differences in Liver Transplantation and Post–Liver Transplant Survival Among Patients With Hepatocellular Carcinoma","authors":"Udhayvir S. Grewal,&nbsp;Apoorva K. Chandar,&nbsp;Shiva J. Gaddam,&nbsp;Abdul Rahman Al Armashi,&nbsp;Akram Alkreshi,&nbsp;Subhash C. Garikipati","doi":"10.1002/cam4.70298","DOIUrl":"10.1002/cam4.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Racial and ethnic disparities in diagnosis and overall outcomes for HCC are well known. We present updated real-world data on racial or ethnic differences in LT and post-LT survival among patients with HCC in a large population-based database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used the TriNetX database to retrospectively identify patients who had HCC (ICD-10 C22.0, C22.8) and underwent LT (CPT codes 47,135, 47,140, 47,140, 47,141, 47,142) from 2012 to 2022 and compared outcomes across racial and ethnic subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Majority of the patients were Caucasians (2403/2901, 84.8%), followed by African Americans (267/2901, 9.2%) Hispanic/Asian (231/2901, 7.9%). At follow up of 5 years, we noted no significant difference in mortality between AA and Caucasian patients [HR = 1.087 (95% CI 0.76, 1.56, <i>p</i> = 0.59)] as well as Hispanic/Asian and Caucasian patients [HR = 1.14 (95% CI 0.73, 1.78, <i>p</i> = 0.10)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate that stringent implementation of policies aimed at ensuring equitable access to LT may contribute to bridging disparities in overall outcomes in HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Correlation Between the Natural Course, Pathologic Properties With Ki-67 Expression in Lung Adenocarcinoma Presenting as Ground-Glass Nodules","authors":"Shaohui Huang,&nbsp;Huanhuan Zhou,&nbsp;Chenchen Lin,&nbsp;Ziqi Wang,&nbsp;Lijun Shen,&nbsp;Ya Sun,&nbsp;Meihui Wei,&nbsp;Zhiwei Xu,&nbsp;Xiaoju Zhang","doi":"10.1002/cam4.70390","DOIUrl":"10.1002/cam4.70390","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With the increasing use of lung cancer screening, the detection of ground glass nodules (GGNs) has risen. However, the natural course of GGNs and their relationship to pathologic features remains unclear. Differentiating between invasive and pre-invasive lesions based on GGN growth may improve clinical intervention timing. Ki-67, a proliferation marker, holds value in assessing tumor malignancy. This study analyzes the association between GGN growth, pathology, and Ki-67 expression to provide new insights into early-stage lung cancer management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively evaluated 183 GGNs with at least two preoperative CT scans. Nodule location, type, natural course, and volume doubling time (VDT) were compared between invasive adenocarcinoma (IAC) and pre-IAC groups. We also assessed differences in Ki-67 expression and correlated VDT with Ki-67 levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 183 nodules were finally included; gender, nodule location, smoking history, and duration of follow-up did not differ between the IAC group and the pre-IAC group, whereas age was statistically different between the two groups. Of the 183 nodules, 52 showed growth and the predominant pathologic type was IAC, these IACs showed more PSN in nodule type, while the IAC group showed more significant differences in nodule type, nodules growth, and VDT than the pre-IAC group. There were also differences in pathologic type and VDT between different Ki-67 expression groups, and Ki-67 expression gradually increased as VDT decreased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) presenting as GGNs exhibit distinct natural courses among pathologic subtypes. VDT effectively distinguishes these growth characteristics, with IACs showing shorter VDT. The significant correlation between VDT and Ki-67 expression suggests that combining these parameters may provide valuable insights into the biological behavior and invasiveness of LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma","authors":"Janith A. Seneviratne,&nbsp;Daenikka Ravindrarajah,&nbsp;Daniel R. Carter,&nbsp;Vicki Zhai,&nbsp;Amit Lalwani,&nbsp;Sukriti Krishan,&nbsp;Anushree Balachandran,&nbsp;Ernest Ng,&nbsp;Ruby Pandher,&nbsp;Matthew Wong,&nbsp;Tracy L. Nero,&nbsp;Shudong Wang,&nbsp;Murray D. Norris,&nbsp;Michelle Haber,&nbsp;Tao Liu,&nbsp;Michael W. Parker,&nbsp;Belamy B. Cheung,&nbsp;Glenn M. Marshall","doi":"10.1002/cam4.70082","DOIUrl":"10.1002/cam4.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The child cancer, neuroblastoma (NB), is characterised by a low incidence of mutations and strong oncogenic embryonal driver signals. Many new targeted epigenetic modifier drugs have failed in human trials as monotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a high-throughput, combination chromatin-modifier drug screen against NB cells. We screened 13 drug candidates in 78 unique combinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the combination of two histone methyltransferase (HMT) inhibitors: GSK343, targeting EZH2, and SGC0946, targeting DOT1L, demonstrated the strongest synergy across 8 NB cell lines, with low normal fibroblast toxicity. High mRNA expression of both EZH2 and DOT1L in NB tumour samples correlated with the poorest patient survival. Combination HMT inhibitor treatment caused activation of ATF4-mediated endoplasmic reticulum (ER) stress responses. In addition, glutathione and several amino acids were depleted by HMT inhibitor combination on mass spectrometry analysis. The combination of SGC0946 and GSK343 reduced tumour growth in comparison to single agents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results support further investigation of HMT inhibitor combinations as a therapeutic approach in NB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}