International Journal of Cancer最新文献_第3页

Smoking behavior and the risks of tumor recurrence and progression in patients with non-muscle-invasive bladder cancer. 吸烟行为与非肌层浸润性膀胱癌患者肿瘤复发和恶化的风险。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-11-05 DOI: 10.1002/ijc.35250

Joann Kiebach, Ivy Beeren, Katja K H Aben, J Alfred Witjes, Antoine G van der Heijden, Lambertus A L M Kiemeney, Alina Vrieling

{"title":"Smoking behavior and the risks of tumor recurrence and progression in patients with non-muscle-invasive bladder cancer.","authors":"Joann Kiebach, Ivy Beeren, Katja K H Aben, J Alfred Witjes, Antoine G van der Heijden, Lambertus A L M Kiemeney, Alina Vrieling","doi":"10.1002/ijc.35250","DOIUrl":"https://doi.org/10.1002/ijc.35250","url":null,"abstract":"Studies on the relationship of cigarette smoking with the risks of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) are inconsistent and prospective data are scarce. Therefore, we aimed to assess the association of smoking behavior with risks of NMIBC recurrence and progression. We used data of the prospective multi-center cohort study UroLife, including 1495 patients with NMIBC who reported information on smoking at 6 weeks post-diagnosis (baseline; reflecting present and pre-diagnosis). This included smoking status (also based on reporting 3 months post-diagnosis), intensity, duration, pack years, and time since smoking cessation, if applicable. Hazard ratios and 95% confidence intervals (CIs) for risks of first recurrence, multiple recurrences, and progression were computed using multivariable proportional hazards regression models. During a total median follow-up period of 4.6 years, 517 patients developed ≥1 recurrence and 163 had progression. Higher versus lowest categories of smoking intensities and pack years up to baseline were significantly associated with a higher risk of first recurrence. No significant linear associations were found, except for smoking intensity among BCG-treated patients (per 10 cigarettes/day increase: HR 1.23, 95%CI 1.02, 1.48). No associations for smoking status, duration, and time since cessation were observed. Analyses of multiple recurrence risk showed comparable results. Regarding progression risk, no consistent associations were found. In conclusion, heavier smoking was associated with higher recurrence risk, particularly among BCG-treated patients. This may be attributable to persistent damage through its carcinogenic compounds. Given the mixed results across different exposures, the effect of smoking behavior on NMIBC prognosis remains unclear.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women. 总睾酮、性激素结合球蛋白和游离睾酮浓度与原发性肝癌风险：对 20 万名男性和 18 万名绝经后女性的前瞻性分析。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-11-05 DOI: 10.1002/ijc.35244

Cody Z Watling, Rebecca K Kelly, Eleanor L Watts, Barry I Graubard, Jessica L Petrick, Charles E Matthews, Katherine A McGlynn

{"title":"Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.","authors":"Cody Z Watling, Rebecca K Kelly, Eleanor L Watts, Barry I Graubard, Jessica L Petrick, Charles E Matthews, Katherine A McGlynn","doi":"10.1002/ijc.35244","DOIUrl":"https://doi.org/10.1002/ijc.35244","url":null,"abstract":"In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR2) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer. After a median of 11.8 years of follow-up, 531 cases of primary liver cancer were observed, of which 366 occurred in males and 165 occurred in females. Total testosterone and SHBG were shown to be positively associated with liver cancer risk in both males and females (Total testosterone HR2: 3.42, 95% CI:2.42-4.84 and 1.29, 0.97-1.72, respectively; SHBG HR2: 5.44, 4.42-6.68 and 1.52, 1.09-2.12, respectively). However, free testosterone was inversely associated with primary liver cancer in males (HR2: 0.42, 0.32-0.55) and no association was observed in females. When analyses compared two main liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), there was evidence of heterogeneity; associations for total testosterone and SHBG concentrations were only positively associated with HCC in both males (HR2: 3.56, 2.65-4.79 and 7.72, 6.12-9.73, respectively) and females (HR2: 1.65, 1.20-2.27 and 6.74, 3.93-11.5, respectively) but not with ICC. Further research understanding the mechanisms of how sex-steroids may influence liver cancer risk is needed.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nationwide cohort study on the risk of high-grade cervical dysplasia and carcinoma after conservative treatment or hysterectomy for adenocarcinoma in situ. 关于原位腺癌保守治疗或子宫切除术后高级别宫颈发育不良和癌变风险的全国队列研究。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-11-04 DOI: 10.1002/ijc.35237

Mirte Schaafsma, Teska N Schuurman, Pien Kootstra, Deli Issa, Ivo Hermans, Maaike C G Bleeker, Petra L M Zusterzeel, Ruud L M Bekkers, Albert G Siebers, Constantijne H Mom, Nienke E van Trommel

{"title":"Nationwide cohort study on the risk of high-grade cervical dysplasia and carcinoma after conservative treatment or hysterectomy for adenocarcinoma in situ.","authors":"Mirte Schaafsma, Teska N Schuurman, Pien Kootstra, Deli Issa, Ivo Hermans, Maaike C G Bleeker, Petra L M Zusterzeel, Ruud L M Bekkers, Albert G Siebers, Constantijne H Mom, Nienke E van Trommel","doi":"10.1002/ijc.35237","DOIUrl":"https://doi.org/10.1002/ijc.35237","url":null,"abstract":"Internationally, little consensus exists about the best treatment for cervical adenocarcinoma in situ (AIS). This study aimed to determine the incidence of recurrent high-grade cervical dysplasia and development of local cervical cancer after treatment for AIS. This nationwide, retrospective cohort study included patients with AIS, who were treated by a large loop excision of the transformation zone (LLETZ), cold-knife conization (CKC), or hysterectomy between January 1, 1990 and December 31, 2021 in the Netherlands. Pathology reports were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were the cumulative incidences of high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2 or 3, and AIS) and local cervical cancer up to 20 years after primary treatment. In total, 4243 patients with AIS were included. The primary treatment was a LLETZ, CKC, or hysterectomy in 1593, 2118, and 532 patients, respectively. The incidence of recurrent high-grade cervical dysplasia after LLETZ (10.5%; 95%CI: 8.6-12.3) was higher than after CKC (5.5%; 95%CI: 4.4-6.6, p <.0001). When a radical excision, that is, surgical margins free of dysplasia at end of treatment, was achieved, the incidence of recurrent high-grade dysplasia and local cervical cancer did not differ between LLETZ (5.6% [95%CI: 3.3-7.9] and 1.9% [95%CI: 0-4.4]) and CKC (4.7% [95%CI: 3.5-5.8], p = .631 and 1.5% [95%CI: 0.7-2.3], p = .918). After hysterectomy, none of the patients developed cervical dysplasia or local cervical cancer. Conservative treatment for AIS can be considered a safe and final treatment modality when a radical excision is achieved.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Influence of therapy exposures on specific late morbidities, prescription drug purchases, and mortality in aging male survivors of childhood cancer: A registry-based study. 治疗暴露对老年男性儿童癌症幸存者特定晚期疾病、处方药购买和死亡率的影响：一项基于登记的研究。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-11-04 DOI: 10.1002/ijc.35247

Mikael Koskela, Melanie Korhonen, Anu Haavisto, Kirsi Jahnukainen

{"title":"Influence of therapy exposures on specific late morbidities, prescription drug purchases, and mortality in aging male survivors of childhood cancer: A registry-based study.","authors":"Mikael Koskela, Melanie Korhonen, Anu Haavisto, Kirsi Jahnukainen","doi":"10.1002/ijc.35247","DOIUrl":"https://doi.org/10.1002/ijc.35247","url":null,"abstract":"Childhood cancer treatments predispose to late health problems and premature death. Our aim was to use national registry data to study associations between cancer therapy exposures and late health outcomes in aging male childhood cancer survivors (CCS). The study comprised 200 male CCS (survival ≥5 years) treated with conventional cancer therapy at a single institution in 1964-2000 and 1000 matched population controls. Analyses involved registry-based data on prescription drug purchases, reimbursements for chronic conditions, hospital admissions, and deaths that occurred ≥5 years after the cancer diagnosis. Mean age of CCS was 45.4 years. Compared to population controls, CCS had a higher risk for hospital admissions due to cardiovascular diseases and late mortality, both of which increased after age 40 years. CCS also had a higher risk for purchases of antihypertensives and lipid-lowering drugs within the last year of the study. Heart radiation ≥10 Gy was associated with hospitalizations due to cardiovascular diseases (HR 4.14, 95%CI 1.81-9.48), purchases of antihypertensives (OR 3.05, 95%CI 1.32-7.36), and purchases of lipid-lowering drugs (OR 2.93, 95%CI 1.08-7.73). Testosterone deficiency developed typically during pediatric follow-up, and it was associated with testicular radiation ≥20 Gy (HR 41.2, 95%CI 15.4-110) but not with alkylating agents. Of patients treated with testicular radiation ≥20 Gy, 91% had purchased testosterone within the last year. Reassuringly, CCS had no excess risk for purchases of opioids, anxiolytics, antiepileptics, or antidepressants. These findings emphasize the need for risk-based follow-up. Middle-aged male CCS are at an increased risk of premature cardiovascular morbidity and excess mortality.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor-derived lactic acid promotes acetylation of histone H3K27 and differentiation of IL-10-producing regulatory B cells through direct and indirect signaling pathways. 肿瘤源乳酸通过直接和间接信号途径促进组蛋白H3K27的乙酰化和产生IL-10的调节性B细胞的分化。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-10-31 DOI: 10.1002/ijc.35229

Satoshi Muraoka, Takashi Baba, Takashi Akazawa, Kei-Ichi Katayama, Hiroki Kusumoto, Shimpei Yamashita, Yasuo Kohjimoto, Sadahiro Iwabuchi, Shinichi Hashimoto, Isao Hara, Norimitsu Inoue

{"title":"Tumor-derived lactic acid promotes acetylation of histone H3K27 and differentiation of IL-10-producing regulatory B cells through direct and indirect signaling pathways.","authors":"Satoshi Muraoka, Takashi Baba, Takashi Akazawa, Kei-Ichi Katayama, Hiroki Kusumoto, Shimpei Yamashita, Yasuo Kohjimoto, Sadahiro Iwabuchi, Shinichi Hashimoto, Isao Hara, Norimitsu Inoue","doi":"10.1002/ijc.35229","DOIUrl":"https://doi.org/10.1002/ijc.35229","url":null,"abstract":"Tumor cells are known to enhance glycolysis, even under normoxic conditions, via the Warburg effect, producing excess lactic acid in the tumor microenvironment. Lactic acid enhances the IL-23/IL-17 pathway and induces chronic inflammation. The acidic microenvironment formed by lactic acid suppresses immune cell proliferation and activation. In the present study, we clarified that lactic acid had two novel activities for immune cells. First, lactic acid specifically enhanced acetylation at lysine 27 of histone H3 (H3K27ac) in splenic B cells and monocytes/macrophages, and this epigenetically up-regulates the expression of genes. Acetylation and methylation of other residues of histone H3 were rarely induced. Second, lactic acid induced a particularly-marked enhancement of Il10 gene expression in B cells, leading to an increase in IL-10-producing regulatory B (Breg) cells. Furthermore, two pathways should be involved in both the enhancement of H3K27ac and the induction of Breg cells by lactic acid: a direct pathway that enhances the CD40 signal in B cells, and an indirect pathway that affects B cells by activating the exchange protein directly activated by cAMP (EPAC) 1/2 in non-B cells. In tumor-bearing mice, the levels of H3K27ac of tumor-infiltrating B cells were significantly higher than splenic B cells and were suppressed by intraperitoneal injection of the EPAC1/2 inhibitor. In conclusion, tumor-derived lactic acid increases H3K27ac and IL-10-producing Breg cells, causing the suppression of anti-tumor immunity.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-steroidal anti-inflammatory drug use and inflammatory markers associated with gallbladder dysplasia: A case-control analysis within a series of patients undergoing cholecystectomy. 非甾体类抗炎药物的使用与胆囊发育不良相关的炎症指标：对一系列接受胆囊切除术的患者进行的病例对照分析。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-10-31 DOI: 10.1002/ijc.35238

Lorena Rosa, Paz Cook, Ruth M Pfeiffer, Troy J Kemp, Allan Hildesheim, Burcin Pehlivanoglu, Volkan Adsay, Enrique Bellolio, Juan Carlos Araya, Ligia Pinto, Catterina Ferreccio, Gloria Aguayo, Eduardo Viñuela, Jill Koshiol

{"title":"Non-steroidal anti-inflammatory drug use and inflammatory markers associated with gallbladder dysplasia: A case-control analysis within a series of patients undergoing cholecystectomy.","authors":"Lorena Rosa, Paz Cook, Ruth M Pfeiffer, Troy J Kemp, Allan Hildesheim, Burcin Pehlivanoglu, Volkan Adsay, Enrique Bellolio, Juan Carlos Araya, Ligia Pinto, Catterina Ferreccio, Gloria Aguayo, Eduardo Viñuela, Jill Koshiol","doi":"10.1002/ijc.35238","DOIUrl":"https://doi.org/10.1002/ijc.35238","url":null,"abstract":"Inflammation has been associated with the development of gallbladder cancer (GBC). However, little is known about the associations of both, inflammation and the use of non-steroidal anti-inflammatory drugs (NSAIDs), with preneoplastic lesions. We analyzed the association of NSAIDs and gallbladder dysplasia in 82 patients with dysplasia and 1843 patients with gallstones among symptomatic patients from a high-risk population. We also analyzed associations for 33 circulating immune-related proteins in a subsample of all 68 dysplasia cases diagnosed at the time of sample selection and 136 gallstone controls. We calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Biliary colic was reported among most cases (97.6%) and controls (83.9%). NSAID use was inversely associated with gallbladder dysplasia (OR: 0.48, 95%CI: 0.26-0.83). Comparing the highest versus lowest category of each immune-related protein, eight proteins were inversely associated with dysplasia with sex- and age-adjusted ORs ranging from 0.30 (95%CI: 0.12-0.77) for IL-33 to 0.76 (95%CI: 0.59-0.99) for MIP-1B. Of those, GRO remained associated with dysplasia (OR: 0.64, 95%CI: 0.45-0.91) and BCA-1 was borderline associated (OR: 0.74, 95%CI: 0.54-1.01) after adjusting the logistic regression model for sex, age, and NSAIDs. In conclusion, NSAID users were less likely to have gallbladder dysplasia, suggesting that NSAIDs might be beneficial for symptomatic gallstones patients. The inverse association between immune-related markers and dysplasia requires additional research, ideally in prospective studies with asymptomatic participants, to understand the role of the inflammatory response in the natural history of GBC and to address the biological effect of NSAIDs.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered exosomes in service of tumor immunotherapy: From optimizing tumor-derived exosomes to delivering CRISPR/Cas9 system. 为肿瘤免疫疗法服务的工程外泌体：从优化肿瘤外泌体到提供CRISPR/Cas9系统。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-10-30 DOI: 10.1002/ijc.35241

Mingyang Jiang, Ke Zhang, Jinfeng Meng, Linhua Xu, Ying Liu, Ruqiong Wei

{"title":"Engineered exosomes in service of tumor immunotherapy: From optimizing tumor-derived exosomes to delivering CRISPR/Cas9 system.","authors":"Mingyang Jiang, Ke Zhang, Jinfeng Meng, Linhua Xu, Ying Liu, Ruqiong Wei","doi":"10.1002/ijc.35241","DOIUrl":"https://doi.org/10.1002/ijc.35241","url":null,"abstract":"Exosomes can be modified and designed for various therapeutic goals because of their unique physical and chemical characteristics. Researchers have identified tumor-derived exosomes (TEXs) as significant players in cancer by influencing tumor growth, immune response evasion, angiogeneis, and drug resistance. TEXs promote the production of specific proteins important for cancer progression. Due to their easy accessibility, TEXs are being modified through genetic, drug delivery, membrane, immune system, and chemical alterations to be repurposed as vehicles for delivering drugs to improve cancer treatment outcomes. In the complex in vivo environment, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) system encounters challenges from degradation, neutralization, and immune responses, emphasizing the need for strategic distribution strategies for effective genome editing. Engineered exosomes present a promising avenue for delivering CRISPR/Cas9 in vivo. In this review, we will explore different techniques for enhancing TEXs using various engineering strategies. Additionally, we will discuss how these exosomes can be incorporated into advanced genetic engineering systems like CRISPR/Cas9 for possible therapeutic uses.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hidden messages in fluids: A review of clinical and fundamental perspectives on post-lymph node dissection drains. 液体中隐藏的信息：淋巴结清扫术后引流的临床和基本观点综述。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-10-29 DOI: 10.1002/ijc.35240

Chon-Hou Mak, Guang-Rui Wang, Zi-Zhan Li, Lei-Ming Cao, Chen-Xi Zhang, Zhao-Qi Zhu, Bing Liu, Lin-Lin Bu

引用次数: 0

ARP2/3 complex affects myofibroblast differentiation and migration in pancreatic ductal adenocarcinoma. ARP2/3 复合物影响胰腺导管腺癌的肌成纤维细胞分化和迁移。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-10-29 DOI: 10.1002/ijc.35246

Yifeng Sun, Yina Qiao, Yiqi Niu, Bindhu Kollivayal Madhavan, Chao Fang, Jingxiong Hu, Kathleen Schuck, Benno Traub, Helmut Friess, Ingrid Herr, Christoph W Michalski, Bo Kong

{"title":"ARP2/3 complex affects myofibroblast differentiation and migration in pancreatic ductal adenocarcinoma.","authors":"Yifeng Sun, Yina Qiao, Yiqi Niu, Bindhu Kollivayal Madhavan, Chao Fang, Jingxiong Hu, Kathleen Schuck, Benno Traub, Helmut Friess, Ingrid Herr, Christoph W Michalski, Bo Kong","doi":"10.1002/ijc.35246","DOIUrl":"https://doi.org/10.1002/ijc.35246","url":null,"abstract":"The ARP2/3 complex, which orchestrates actin cytoskeleton organization and lamellipodia formation, has been implicated in the initiation of pancreatic ductal adenocarcinoma (PDAC). This study aims to clarify its impact on the activity of cancer-associated fibroblasts (CAFs), key players in PDAC progression, and patient outcomes. Early pancreatic carcinogenesis was modeled in p48Cre; LSL-KrasG12D mice with caerulein-induced pancreatitis, complemented by in vitro studies on human immortalized pancreatic stellate cells (PSCs) and primary PDAC-derived CAFs. Data were gained from microarray analysis, RNA sequencing (RNA-seq), and single-cell RNA sequencing (sc-RNA-seq), with subsequent bioinformatics analysis. We uncovered a specific transcriptional signature associated with fibroblast migration in early pancreatic carcinogenesis and linked it to poor survival in patients with PDAC. A pivotal role of the ARP2/3 complex in CAF migration was identified. Inhibition of the ARP2/3 complex markedly decreased CAF motility and induced significant morphological changes in vitro. Furthermore, its inhibition also hindered TGFβ1-mediated myofibroblastic CAF differentiation but had no effect on IL-1-mediated inflammatory CAF differentiation. Our findings position the ARP2/3 complex as central to the migration and differentiation of myofibroblastic CAF. Targeting this complex presents a promising new therapeutic avenue for PDAC treatment.","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comment on "Postmarketing adverse events of tamoxifen in male and female patients with breast cancer". 就 "他莫昔芬在男性和女性乳腺癌患者中的上市后不良事件 "发表评论。

IF 5.7 2区医学

International Journal of Cancer Pub Date : 2024-10-29 DOI: 10.1002/ijc.35243

Yoshihiro Noguchi, Yoko Ino, Ryo Kobayashi, Tomoaki Yoshimura

引用次数: 0