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circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-27 DOI: 10.1002/cam4.70729
Wei Chen, Weijun Zhao, Xianqiao Wu, Tianzheng Fang, Ziyuan Chen, Zixuan Chen, Wenmin Su, Xiaodong Zhao, Yuanyuan Hu, Yiping Xu, Shuai Fang, Chengwei Zhou

Background

Lung cancer has a notably high incidence and mortality rate, and understanding its occurrence and development is crucial for effective treatment. Circular RNA is closely associated with tumor progression, playing a role in tumorigenesis and development by regulating gene expression and influencing cell proliferation and apoptosis. This study aims to explore the circFOXK2 role in NSCLC occurrence and development and to elucidate its underlying mechanisms.

Methods

qRT-PCR and Western Blot analyzed the expressions of circFOXK2, STMN1, and PABPCA in NSCLC cell lines, as well as their relationships. The roles of circFOXK2 and STMN1 in the proliferation, invasion, and migration of NSCLC cells were assessed through CCK8, EDU, and Transwell experiments. RNA pulldown assays with mass spectrometry elucidated the RNA-binding proteins of circFOXK2. Subcutaneous tumorigenesis and tail vein lung metastasis experiments analyzed the impact of circFOXK2 on tumor growth and metastasis in vivo.

Results

In this study, we identified circFOXK2, which is significantly overexpressed in NSCLC, through bioinformatics screening. Elevated levels of circFOXK2 enhance the growth and metastasis of NSCLC cells. Furthermore, through experiments such as co-IP and mass spectrometry, we found that circFOXK2 interacts with PABPC1 to form a complex, which correlates positively with the progression and metastasis of tumors. Simultaneously, the circFOXK2/PABPC1 complex increases the stability of STMN1 mRNA, thereby promoting the transcription and translation of STMN1. Our experimental results indicate that the oncogenic effect of circFOXK2 requires the assistance of STMN1.

Conclusions

In summary, we have demonstrated the significant role of circFOXK2/PABPC1 in regulating STMN1 expression in NSCLC.

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引用次数: 0
CAR-T Cell Manufacturing for Hematological and Solid Tumors: From the Preclinical to Clinical Point of View
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-27 DOI: 10.1002/cam4.70726
Sara Capolla, Maria Rasool, Giuseppe Toffoli, Michele Dal Bo

Cell therapy based on chimeric antigen receptor (CAR) T cells has represented a revolutionary new approach for treating tumors, especially hematological diseases. Complete remission rates (CRR) > 80%–97% and 50%–90% overall response rates (ORR) have been achieved with a treatment based on CAR-T cells in patients with malignant B-cell tumors that have relapsed or are refractory to previous treatments. Toxicity remains the major problem. Most patients treated with CAR-T cells develop high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). However, the unprecedentedly high CRR and ORR have led to the approval of six CAR-T cell therapeutics by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), prompting researchers to improve existing products and develop new ones. By now, around 1000 clinical trials based on CAR-T cells are registered at ClinicalTrials.gov: 82% are for hematological diseases, while the remaining 16% are for solid tumors. As a result of this increased research, an enormous amount of conflicting information has been accumulated in the literature, and each group follows its manufacturing protocols and performs specific in vitro testing. This review aimed to combine and compare clinical and preclinical information, highlighting the most used protocols to provide a comprehensive overview of the in vitro world of CAR-T cells, from manufacturing to their characterization. The focus is on all steps of the CAR-T cell manufacturing process, from the collection of patient or donor blood to the enrichment of T cells, their activation with anti-CD3/CD28 beads, interleukin-2 (IL-2) or IL-7 and IL-15 (induction of a more functional memory phenotype), and their transfection (viral or non-viral methods). Automation is crucial for ensuring a standardized final product.

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引用次数: 0
DGKα Enhances Tumorigenic Activity in Bladder Cancer Patients With Chronic Kidney Disease
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-27 DOI: 10.1002/cam4.70710
Kenshiro Takemoto, Kohei Kobatake, Tomoya Hatayama, Shinsaku Tasaka, Mai Okazaki, Yoshinori Nakano, Hiroyuki Shikuma, Kazuma Yukihiro, Kyosuke Iwane, Ryoken Yamanaka, Ryo Tasaka, Yuki Kohada, Miki Naito, Shunsuke Miyamoto, Yohei Sekino, Hiroyuki Kitano, Keisuke Goto, Akihiro Goriki, Keisuke Hieda, Nobuyuki Hinata

Introduction

Chronic kidney disease (CKD) is a risk factor for bladder cancer (BC) and is reportedly involved in its recurrence and progression. This study aimed to determine the molecular mechanisms underlying the development of BC in patients with CKD.

Methods

First, we generated the CKD mouse model according to a unilateral two-stage renal ischemia–reperfusion injury protocol using wild-type C57BL/6 mice. Second, we conducted a molecular functional analysis of DGKα in BC and investigated the contribution of DGKα to cell invasion, migration, and proliferation activity using human BC cell lines.

Results

After confirming elevated serum creatinine levels in mice, the bladder was dissected, and mRNA sequencing of bladder urothelial cells was conducted. Gene expression profiling revealed remarkable upregulation in diacylglycerol kinase alpha (DGKα) level compared to that in control urothelial cells. DGKα-knockdown cells displayed significantly decreased invasion, migration, and proliferation activity compared to the controls. Next, we conducted a clinical analysis of DGKα in BC patients and performed immunohistochemistry (IHC) on samples from patients treated with radical cystectomy. IHC staining revealed that DGKα-positive cases had significantly worse recurrence-free and cancer-specific survival rates (p = 0.036 and = 0.003, respectively).

Conclusion

DGKα expression is associated with tumorigenic activity in BC. Therefore, it is speculated that increased expression of DGKα in CKD cases is involved in the malignant potentials in BC. In conclusion, the crucial role of DGKα in BC is suggested, and it may be one of the factors contributing to poor prognosis in BC patients with CKD.

{"title":"DGKα Enhances Tumorigenic Activity in Bladder Cancer Patients With Chronic Kidney Disease","authors":"Kenshiro Takemoto,&nbsp;Kohei Kobatake,&nbsp;Tomoya Hatayama,&nbsp;Shinsaku Tasaka,&nbsp;Mai Okazaki,&nbsp;Yoshinori Nakano,&nbsp;Hiroyuki Shikuma,&nbsp;Kazuma Yukihiro,&nbsp;Kyosuke Iwane,&nbsp;Ryoken Yamanaka,&nbsp;Ryo Tasaka,&nbsp;Yuki Kohada,&nbsp;Miki Naito,&nbsp;Shunsuke Miyamoto,&nbsp;Yohei Sekino,&nbsp;Hiroyuki Kitano,&nbsp;Keisuke Goto,&nbsp;Akihiro Goriki,&nbsp;Keisuke Hieda,&nbsp;Nobuyuki Hinata","doi":"10.1002/cam4.70710","DOIUrl":"https://doi.org/10.1002/cam4.70710","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Chronic kidney disease (CKD) is a risk factor for bladder cancer (BC) and is reportedly involved in its recurrence and progression. This study aimed to determine the molecular mechanisms underlying the development of BC in patients with CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, we generated the CKD mouse model according to a unilateral two-stage renal ischemia–reperfusion injury protocol using wild-type C57BL/6 mice. Second, we conducted a molecular functional analysis of DGKα in BC and investigated the contribution of DGKα to cell invasion, migration, and proliferation activity using human BC cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After confirming elevated serum creatinine levels in mice, the bladder was dissected, and mRNA sequencing of bladder urothelial cells was conducted. Gene expression profiling revealed remarkable upregulation in diacylglycerol kinase alpha (DGKα) level compared to that in control urothelial cells. DGKα-knockdown cells displayed significantly decreased invasion, migration, and proliferation activity compared to the controls. Next, we conducted a clinical analysis of DGKα in BC patients and performed immunohistochemistry (IHC) on samples from patients treated with radical cystectomy. IHC staining revealed that DGKα-positive cases had significantly worse recurrence-free and cancer-specific survival rates (<i>p</i> = 0.036 and = 0.003, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DGKα expression is associated with tumorigenic activity in BC. Therefore, it is speculated that increased expression of DGKα in CKD cases is involved in the malignant potentials in BC. In conclusion, the crucial role of DGKα in BC is suggested, and it may be one of the factors contributing to poor prognosis in BC patients with CKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497139","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}
引用次数: 0
Follow-Up Adherence After Treatment With Curative Intent for Stage II and III Colorectal Cancer Patients
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-27 DOI: 10.1002/cam4.70667
Tara C. Boute, Rik van Eekelen, Marloes A. G. Elferink, Lissenberg Witte Birgit I, Johannes H. W. de Wilt, Geraldine R. Vink, Marjolein J. E. Greuter, Veerle M. H. Coupé

Introduction

After colorectal cancer (CRC) treatment, patients undergo five-year follow-up involving carcinoembryonic antigen (CEA) tests, imaging, and colonoscopies. This retrospective cohort study explores adherence to the CRC follow-up guideline in the Netherlands until 2021 and its association with treatment of recurrences with curative intent.

Methods

Stage II/III CRC patients with recurrent disease within 3 years after diagnosis were selected from the Netherlands Cancer Registry (n = 430). Adherence to CEA tests, imaging, and colonoscopy was classified as ‘according to/more follow-up’ or ‘less follow-up’ than recommended. Logistic regression analyses examined factors associated with receiving less follow-up and the relationship between ‘follow-up adherence’ and ‘treatment with curative intent’, potentially mediated by ‘mode of detection’ (symptomatically vs. routine test).

Results

In total, 18.3% patients had fewer CEA tests, 41.4% fewer imaging, and 56.1% fewer colonoscopies than recommended. Factors associated with fewer follow-up moments were tumor localization, age (≥ 75 years), comorbidities, tumor differentiation and adjuvant chemotherapy. Patients receiving fewer CEA tests faced 4.8 times higher odds (95% CI: 2.9–8.1) of symptom-detected recurrence and were less likely to be curatively treated (OR = 0.5; 95% CI: 0.3–0.9). Mediation analysis indicated a significant average causal mediation effect (p = 0.003), emphasizing the mediating role of mode of detection. Receiving fewer imaging and colonoscopies showed insignificant total effects on treatment with curative intent.

Conclusion

Our findings offer insights into follow-up adherence, detection mode, and treatment with curative intent. The discovery that adherence was highest for CEA, along with the correlation between CEA adherence and treatment with curative intent, aligns with the recent adaptation of guidelines emphasizing CEA measurement over imaging.

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引用次数: 0
Licorice Extract Isoliquiritigenin Increased Cytosol Calcium and Induced Apoptosis in Colon Cancer Cells via Transient Receptor Potential Vanilloid-1
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-27 DOI: 10.1002/cam4.70705
Lin Wang, Qing Li, Lai Kwok Leung, Wing Tak Wong

Background

Colorectal cancer (CRC) is the third most common malignant tumor, and the fifth cause of cancer-related death in China, while chemotherapy is the primary strategy for CRC. Transient receptor potential (TRP) channels are non-selective cation channels while modulating the expression or activity of TRP channels results in the regulation of Ca2+ influx. Previous studies have shown that TRP members with altered expression or channel activity are presented in CRC cells, which made them become promising therapeutic targets. Isoliquiritigenin (ISL), one of the major bioactive ingredients from traditional Chinese medicine licorice, was reported to exhibit anti-cancer properties such as induce apoptosis in CRC cells, but the underlying mechanism was not fully understood, whether its anticancer activity was related to regulating intracellular calcium and TRP channels remains for further investigation.

Objective

The study aims to investigate the effect of ISL on altering cytosol calcium in CRC cells and elucidate its potential molecular mechanism.

Methods

The study was conducted on 2 CRC cell lines HT29 and HCT116. Changes of cytosol calcium was indicated by live cell Ca2+ imaging. Expression level of TRPV1 was determined by western blot. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining.

Results

ISL significantly increased cytosol calcium in HT29 and HCT116 cells. The ISL-induced increasing calcium ions were from both calcium influx and intracellular calcium release. ISL co-culture directly upregulated the expression of transient receptor potential vanilloid-1 (TRPV1) in colon cancer cells. Inhibition of TRPV1 by capsazepine (CapZ) abrogated the ISL-induced calcium influx and ISL-induced apoptosis in HT29 and HCT116 cells.

Conclusions

This study illustrates, for the first time, that ISL increased cytosol calcium concentration and induced apoptosis via TRPV1 in colon cancer cells, giving a new understanding of the underlying mechanism of its anti-cancer ability and making it a potential regulator for TRPV1.

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引用次数: 0
Acceptability of Home-Based Urine Self-Collection for Cervical Cancer Screening Among Women Receiving Care at the Arab Community Center for Economic and Social Services in Michigan
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-26 DOI: 10.1002/cam4.70714
Timothy C. Guetterman, Christelle El Khoury, Madiha Tariq, Ghada Aziz, Asraa Alhawli, Martha L. Alves, Elizabeth Haro, Emma A. Butcher, Alexandra H. Vinson, Diane M. Harper

Background

Michigan's Middle Eastern-North African (MENA) community is an essential and growing part of the state's population. However, MENA individuals are underrepresented in the research literature due to a lack of recognized demographic categorization. Prior work shows that MENA women face barriers to traditional clinician-directed cervical cancer screening. This study aims to capture the perspectives of MENA women about home-based urine cervical cancer screening using HPV kits and to assess whether such methods could positively impact future screening intent.

Methods

Through collaboration with a community partner in southeast Michigan, we recruited MENA women ages 30–65, with 44 completing the study. Participants used urine HPV self-sampling kits at home and then shared their perspectives through a phone interview. We used an inductive, thematic approach to analyze the interviews, which captured experiences with home-based self-sampling, screening preferences, and impact on future screening intent.

Results

Participants found that urine home-based self-sampling was acceptable as a convenient and comfortable way to screen for cervical cancer. Most (80%) preferred self-sampling over traditional clinician-directed screening and preferred collecting urine samples at home (73%) rather than in the clinic. Overall, 80% reported that access to urine self-sampling would positively impact their future screening intent.

Conclusions

MENA participants in this study positively received home-based cervical cancer screening using urine HPV self-sampling kits. These findings support the clinical implementation of self-sampling and home-based cervical cancer screening to increase participation, particularly among those in under-screened communities.

{"title":"Acceptability of Home-Based Urine Self-Collection for Cervical Cancer Screening Among Women Receiving Care at the Arab Community Center for Economic and Social Services in Michigan","authors":"Timothy C. Guetterman,&nbsp;Christelle El Khoury,&nbsp;Madiha Tariq,&nbsp;Ghada Aziz,&nbsp;Asraa Alhawli,&nbsp;Martha L. Alves,&nbsp;Elizabeth Haro,&nbsp;Emma A. Butcher,&nbsp;Alexandra H. Vinson,&nbsp;Diane M. Harper","doi":"10.1002/cam4.70714","DOIUrl":"https://doi.org/10.1002/cam4.70714","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Michigan's Middle Eastern-North African (MENA) community is an essential and growing part of the state's population. However, MENA individuals are underrepresented in the research literature due to a lack of recognized demographic categorization. Prior work shows that MENA women face barriers to traditional clinician-directed cervical cancer screening. This study aims to capture the perspectives of MENA women about home-based urine cervical cancer screening using HPV kits and to assess whether such methods could positively impact future screening intent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Through collaboration with a community partner in southeast Michigan, we recruited MENA women ages 30–65, with 44 completing the study. Participants used urine HPV self-sampling kits at home and then shared their perspectives through a phone interview. We used an inductive, thematic approach to analyze the interviews, which captured experiences with home-based self-sampling, screening preferences, and impact on future screening intent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants found that urine home-based self-sampling was acceptable as a convenient and comfortable way to screen for cervical cancer. Most (80%) preferred self-sampling over traditional clinician-directed screening and preferred collecting urine samples at home (73%) rather than in the clinic. Overall, 80% reported that access to urine self-sampling would positively impact their future screening intent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MENA participants in this study positively received home-based cervical cancer screening using urine HPV self-sampling kits. These findings support the clinical implementation of self-sampling and home-based cervical cancer screening to increase participation, particularly among those in under-screened communities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489944","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}
引用次数: 0
Prognostic Impact of Oncogenic Fibroblast Growth Factor Receptor Alterations in Patients With Advanced Solid Tumors in a Real-World Setting
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-25 DOI: 10.1002/cam4.70546
Levon Demirdjian, Spyros Triantos, Kristopher Standish, Shibu Thomas, Qi Xia, Jiarui Zhang, Joel Greshock, Julie Paone, Paige Sheridan, Shubham Pant, Christophe Massard, David A. Reardon, Yohann Loriot, Martin Schuler, Hussein Sweiti

Background

Somatic FGFR gene alterations (FGFRalt) may act as oncogenic drivers across several cancers. The prognostic impact of FGFRalt in solid tumors is not fully understood. We assessed the prognostic impact of FGFRalt on overall survival (OS) in a tumor-agnostic real-world cohort of patients with advanced solid tumors.

Methods

This was a retrospective, observational, comparative cohort analysis that used data from a nationwide de-identified clinico-genomic database. Patients were included if they had advanced/metastatic disease, were aged ≥ 18 years at the time of diagnosis, had evidence of genomic testing for FGFRalt, and had initiated first-line systemic therapy for their cancer. Patients without FGFR alterations (FGFRneg) were matched 3:1 with patients with FGFRalt using a combination of exact matching on tumor type and Mahalanobis-distance matching on selected clinical confounders. The primary endpoint was OS from time of initiation of first-line therapy in patients with FGFRalt versus FGFRneg. To further mitigate bias, delayed entry models and covariate-adjusted stratified Cox models were implemented.

Results

The final cohort included 1012 patients (253 FGFRalt, 759 FGFRneg), across 30 tumor types. There were no significant differences in real-world OS from first-line therapy between FGFRalt and FGFRneg groups (hazard ratio 0.97; p = 0.78). Median OS from initiation of first-line therapy was 1.13 years (95% confidence interval [CI] 0.92–1.52) and 1.01 years (0.89–1.15) for the FGFRalt and FGFRneg groups, respectively.

Conclusions

In this matched-cohort real-world analysis, presence of FGFRalt had no impact on the prognosis of patients with advanced solid tumors receiving standard-of-care treatment.

{"title":"Prognostic Impact of Oncogenic Fibroblast Growth Factor Receptor Alterations in Patients With Advanced Solid Tumors in a Real-World Setting","authors":"Levon Demirdjian,&nbsp;Spyros Triantos,&nbsp;Kristopher Standish,&nbsp;Shibu Thomas,&nbsp;Qi Xia,&nbsp;Jiarui Zhang,&nbsp;Joel Greshock,&nbsp;Julie Paone,&nbsp;Paige Sheridan,&nbsp;Shubham Pant,&nbsp;Christophe Massard,&nbsp;David A. Reardon,&nbsp;Yohann Loriot,&nbsp;Martin Schuler,&nbsp;Hussein Sweiti","doi":"10.1002/cam4.70546","DOIUrl":"https://doi.org/10.1002/cam4.70546","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Somatic <i>FGFR</i> gene alterations (<i>FGFRalt</i>) may act as oncogenic drivers across several cancers. The prognostic impact of <i>FGFRalt</i> in solid tumors is not fully understood. We assessed the prognostic impact of <i>FGFRalt</i> on overall survival (OS) in a tumor-agnostic real-world cohort of patients with advanced solid tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective, observational, comparative cohort analysis that used data from a nationwide de-identified clinico-genomic database. Patients were included if they had advanced/metastatic disease, were aged ≥ 18 years at the time of diagnosis, had evidence of genomic testing for <i>FGFRalt</i>, and had initiated first-line systemic therapy for their cancer. Patients without <i>FGFR</i> alterations (<i>FGFRneg</i>) were matched 3:1 with patients with <i>FGFRalt</i> using a combination of exact matching on tumor type and Mahalanobis-distance matching on selected clinical confounders. The primary endpoint was OS from time of initiation of first-line therapy in patients with <i>FGFRalt</i> versus <i>FGFRneg</i>. To further mitigate bias, delayed entry models and covariate-adjusted stratified Cox models were implemented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final cohort included 1012 patients (253 <i>FGFRalt</i>, 759 <i>FGFRneg</i>), across 30 tumor types. There were no significant differences in real-world OS from first-line therapy between <i>FGFRalt</i> and <i>FGFRneg</i> groups (hazard ratio 0.97; <i>p</i> = 0.78). Median OS from initiation of first-line therapy was 1.13 years (95% confidence interval [CI] 0.92–1.52) and 1.01 years (0.89–1.15) for the <i>FGFRalt</i> and <i>FGFRneg</i> groups, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this matched-cohort real-world analysis, presence of <i>FGFRalt</i> had no impact on the prognosis of patients with advanced solid tumors receiving standard-of-care treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489864","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}
引用次数: 0
Doxorubicin Plus Dacarbazine Versus Doxorubicin Plus Ifosfamide in Combination With Regional Hyperthermia in Patients With Advanced Leiomyosarcoma: A Propensity Score-Matched Analysis 多柔比星加达卡巴嗪与多柔比星加伊福法胺联合区域热疗治疗晚期亮肌肉瘤患者:倾向评分匹配分析
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-25 DOI: 10.1002/cam4.70655
Luc M. Berclaz, Vindi Jurinovic, Anton Burkhard-Meier, Sultan Abdel-Rahman, Markus Albertsmeier, Alexander Klein, Hans Roland Dürr, Nina-Sophie Schmidt-Hegemann, Thomas Knösel, Wolfgang G. Kunz, Emanuel Stutz, Michael von Bergwelt-Baildon, Dorit Di Gioia, Lars H. Lindner

Background

Dacarbazine is currently considered the better combination partner for doxorubicin compared to ifosfamide for the treatment of leiomyosarcoma (LMS). Regional hyperthermia (RHT) combined with neoadjuvant chemotherapy has been shown to improve survival in patients with locally advanced high-risk STS. We sought to evaluate the role of doxorubicin and dacarbazine (AD) versus doxorubicin and ifosfamide (AI) in combination with RHT in patients with LMS.

Methods

Patients with locally advanced high-grade LMS, including limited metastases, eligible for RHT and first-line treatment with either AI + RHT or AD + RHT between 2014 and 2022 were retrospectively evaluated. Endpoints were progression-free survival (PFS) and overall survival (OS). Patients were matched using propensity scores, which were estimated with a logistic regression model accounting for tumor site, presence of metastasis, surgery, and radiotherapy.

Results

A total of 105 patients were included in this study, of which 101 were included in the propensity score-matched cohort. In the matched cohort, treatment with AD + RHT was associated with a significantly improved PFS (HR 0.32, 95% CI 0.13–0.74, p = 0.0081). Multivariable analysis revealed several significant predictors of PFS, including treatment with AD + RHT (HR 0.42, 95% CI 0.19–0.92, p = 0.031).

Conclusion

Treatment with AD + RHT showed improved PFS and better treatment tolerability compared to AI + RHT. Our results support the use of AD instead of AI for the treatment of patients with LMS in combination with RHT.

{"title":"Doxorubicin Plus Dacarbazine Versus Doxorubicin Plus Ifosfamide in Combination With Regional Hyperthermia in Patients With Advanced Leiomyosarcoma: A Propensity Score-Matched Analysis","authors":"Luc M. Berclaz,&nbsp;Vindi Jurinovic,&nbsp;Anton Burkhard-Meier,&nbsp;Sultan Abdel-Rahman,&nbsp;Markus Albertsmeier,&nbsp;Alexander Klein,&nbsp;Hans Roland Dürr,&nbsp;Nina-Sophie Schmidt-Hegemann,&nbsp;Thomas Knösel,&nbsp;Wolfgang G. Kunz,&nbsp;Emanuel Stutz,&nbsp;Michael von Bergwelt-Baildon,&nbsp;Dorit Di Gioia,&nbsp;Lars H. Lindner","doi":"10.1002/cam4.70655","DOIUrl":"https://doi.org/10.1002/cam4.70655","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dacarbazine is currently considered the better combination partner for doxorubicin compared to ifosfamide for the treatment of leiomyosarcoma (LMS). Regional hyperthermia (RHT) combined with neoadjuvant chemotherapy has been shown to improve survival in patients with locally advanced high-risk STS. We sought to evaluate the role of doxorubicin and dacarbazine (AD) versus doxorubicin and ifosfamide (AI) in combination with RHT in patients with LMS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with locally advanced high-grade LMS, including limited metastases, eligible for RHT and first-line treatment with either AI + RHT or AD + RHT between 2014 and 2022 were retrospectively evaluated. Endpoints were progression-free survival (PFS) and overall survival (OS). Patients were matched using propensity scores, which were estimated with a logistic regression model accounting for tumor site, presence of metastasis, surgery, and radiotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 105 patients were included in this study, of which 101 were included in the propensity score-matched cohort. In the matched cohort, treatment with AD + RHT was associated with a significantly improved PFS (HR 0.32, 95% CI 0.13–0.74, <i>p</i> = 0.0081). Multivariable analysis revealed several significant predictors of PFS, including treatment with AD + RHT (HR 0.42, 95% CI 0.19–0.92, <i>p</i> = 0.031).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Treatment with AD + RHT showed improved PFS and better treatment tolerability compared to AI + RHT. Our results support the use of AD instead of AI for the treatment of patients with LMS in combination with RHT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489865","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}
引用次数: 0
RETRACTION: The Role and Molecular Mechanism of Trop2 Induced Epithelial–Mesenchymal Transition Through Mediated β-Catenin in Gastric Cancer
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-23 DOI: 10.1002/cam4.70629

RETRACTION: W. Zhao, L. Jia, X. kuai, Q. Tang, X. Huang, T. Yang, Z. Qiu, J. Zhu, J. Huang, W. Huang, and Z. Feng, “The Role and Molecular Mechanism of Trop2 Induced Epithelial-Mesenchymal Transition Through Mediated β-catenin in Gastric Cancer,” Cancer Medicine 8, no. 3 (2019): 1135–1147, https://doi.org/10.1002/cam4.1934.

The above article, published online on 11 January 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stephen Tait, and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Further investigation by the publisher has unveiled duplication of image elements and/or post-acquisition image manipulation affecting Figures 2B, 3I and S1A. Furthermore, several cell lines used in this study have been reported as problematic (BGC-823 [1, 2], MGC-803 [3, 4], MKN-28 [5] and SGC-7901 [1, 2]). Accordingly, the article must be retracted as its conclusions are considered invalid by the editors. The authors were informed of the decision of retraction but were unavailable for a final confirmation.

{"title":"RETRACTION: The Role and Molecular Mechanism of Trop2 Induced Epithelial–Mesenchymal Transition Through Mediated β-Catenin in Gastric Cancer","authors":"","doi":"10.1002/cam4.70629","DOIUrl":"https://doi.org/10.1002/cam4.70629","url":null,"abstract":"<p><b>RETRACTION</b>: W. Zhao, L. Jia, X. kuai, Q. Tang, X. Huang, T. Yang, Z. Qiu, J. Zhu, J. Huang, W. Huang, and Z. Feng, “The Role and Molecular Mechanism of Trop2 Induced Epithelial-Mesenchymal Transition Through Mediated β-catenin in Gastric Cancer,” <i>Cancer Medicine</i> 8, no. 3 (2019): 1135–1147, https://doi.org/10.1002/cam4.1934.</p><p>The above article, published online on 11 January 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stephen Tait, and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Further investigation by the publisher has unveiled duplication of image elements and/or post-acquisition image manipulation affecting Figures 2B, 3I and S1A. Furthermore, several cell lines used in this study have been reported as problematic (BGC-823 [<span>1, 2</span>], MGC-803 [<span>3, 4</span>], MKN-28 [<span>5</span>] and SGC-7901 [<span>1, 2</span>]). Accordingly, the article must be retracted as its conclusions are considered invalid by the editors. The authors were informed of the decision of retraction but were unavailable for a final confirmation.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475575","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}
引用次数: 0
Heart Rate Variability as a Digital Biomarker in Adolescents and Young Adults Receiving Hematopoietic Cell Transplantation
IF 2.9 2区 医学 Q2 ONCOLOGY Pub Date : 2025-02-21 DOI: 10.1002/cam4.70609
Mallory R. Taylor, Miranda C. Bradford, Chuan Zhou, Kaitlyn M. Fladeboe, Jorie F. Wittig, K. Scott Baker, Joyce P. Yi-Frazier, Abby R. Rosenberg

Introduction

Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk for poor psychosocial outcomes. Heart rate variability (HRV), a surrogate for autonomic nervous system activity, is a promising digital biomarker that has been linked to important outcomes. The objectives of this study were to prospectively describe the trajectory of HRV among AYAs receiving HCT and explore the association between HRV and patient-reported outcomes (PROs).

Methods

This was a multi-site study embedded in a randomized trial among AYAs receiving HCT (NCT03640325). We collected sequential 24-h HRV metrics, including the standard deviation of normal-to-normal beats (SDNN), root-mean-square of successive differences (RMSSD), as well as frequency domain measures. PRO surveys queried anxiety, depression, quality of life, hope, and resilience at baseline and 3 months. We summarized outcomes using descriptive statistics, and Pearson correlation coefficients were used to examine the relationship between HRV and PROs.

Results

Thirty-nine HRV recordings were collected from n = 16 participants aged 12–21 years. There was a moderately strong correlation between inferior baseline HRV and higher anxiety and depression (anxiety: r = −0.35 (p = 0.18) for SDNN, r = −0.47 (p = 0.07) for RMSSD; depression: r = −0.26 (p = 0.34) for SDNN, r = −0.39 (p = 0.14) for RMSSD). Among participants with elevated baseline anxiety, higher HRV suggested greater improvement in anxiety over time (r = −0.66 (p = 0.08) for SDNN, r = −0.31 (p = 0.45) for RMSSD).

Conclusions

There was a correlation between HRV and PROs in this study, and among those with elevated anxiety, HRV predicted improvement over time. Digital biomarkers may augment behavioral intervention design and implementation.

{"title":"Heart Rate Variability as a Digital Biomarker in Adolescents and Young Adults Receiving Hematopoietic Cell Transplantation","authors":"Mallory R. Taylor,&nbsp;Miranda C. Bradford,&nbsp;Chuan Zhou,&nbsp;Kaitlyn M. Fladeboe,&nbsp;Jorie F. Wittig,&nbsp;K. Scott Baker,&nbsp;Joyce P. Yi-Frazier,&nbsp;Abby R. Rosenberg","doi":"10.1002/cam4.70609","DOIUrl":"https://doi.org/10.1002/cam4.70609","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk for poor psychosocial outcomes. Heart rate variability (HRV), a surrogate for autonomic nervous system activity, is a promising digital biomarker that has been linked to important outcomes. The objectives of this study were to prospectively describe the trajectory of HRV among AYAs receiving HCT and explore the association between HRV and patient-reported outcomes (PROs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a multi-site study embedded in a randomized trial among AYAs receiving HCT (NCT03640325). We collected sequential 24-h HRV metrics, including the standard deviation of normal-to-normal beats (SDNN), root-mean-square of successive differences (RMSSD), as well as frequency domain measures. PRO surveys queried anxiety, depression, quality of life, hope, and resilience at baseline and 3 months. We summarized outcomes using descriptive statistics, and Pearson correlation coefficients were used to examine the relationship between HRV and PROs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-nine HRV recordings were collected from <i>n</i> = 16 participants aged 12–21 years. There was a moderately strong correlation between inferior baseline HRV and higher anxiety and depression (anxiety: <i>r</i> = −0.35 (<i>p</i> = 0.18) for SDNN, <i>r</i> = −0.47 (<i>p</i> = 0.07) for RMSSD; depression: <i>r</i> = −0.26 (<i>p</i> = 0.34) for SDNN, <i>r</i> = −0.39 (<i>p</i> = 0.14) for RMSSD). Among participants with elevated baseline anxiety, higher HRV suggested greater improvement in anxiety over time (<i>r</i> = −0.66 (<i>p</i> = 0.08) for SDNN, <i>r</i> = −0.31 (<i>p</i> = 0.45) for RMSSD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There was a correlation between HRV and PROs in this study, and among those with elevated anxiety, HRV predicted improvement over time. Digital biomarkers may augment behavioral intervention design and implementation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455942","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}
引用次数: 0
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Cancer Medicine
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