Pub Date : 2024-07-24DOI: 10.1007/s00432-024-05836-w
Siyu Zhang, Chang Guo, Jun Xu, Pudong Qian, Jiali Guo, Tingting Liu, Yifan Wu, Jun Hong, Qi Wang, Xia He, Li Sun
Background: In single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it.
Methods: We analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors.
Results: The median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1-2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (Rs = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk.
Conclusions: This study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.
{"title":"Quantitative assessment of intertarget position variations based on 4D-CT and 4D-CBCT simulations in single-isocenter multitarget lung stereotactic body radiation therapy.","authors":"Siyu Zhang, Chang Guo, Jun Xu, Pudong Qian, Jiali Guo, Tingting Liu, Yifan Wu, Jun Hong, Qi Wang, Xia He, Li Sun","doi":"10.1007/s00432-024-05836-w","DOIUrl":"10.1007/s00432-024-05836-w","url":null,"abstract":"<p><strong>Background: </strong>In single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it.</p><p><strong>Methods: </strong>We analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors.</p><p><strong>Results: </strong>The median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1-2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (R<sub>s</sub> = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk.</p><p><strong>Conclusions: </strong>This study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Osimertinib resistance prognostic gene signature: STRIP2 is associated with immune infiltration and tumor progression in lung adenocarcinoma.","authors":"Guixing Zhang, Huiting Guan, Yi-Le Ning, Kainan Yao, Hao Tang, Gulizeba Muhetaer, Hang Li, Jihong Zhou","doi":"10.1007/s00432-024-05883-3","DOIUrl":"10.1007/s00432-024-05883-3","url":null,"abstract":"","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1007/s00432-024-05888-y
Simon Bernatz, Falko Schulze, Julia Bein, Katrin Bankov, Scherwin Mahmoudi, Leon D Grünewald, Vitali Koch, Angelika Stehle, Andreas A Schnitzbauer, Dirk Walter, Fabian Finkelmeier, Stefan Zeuzem, Thomas J Vogl, Peter J Wild, Maximilian N Kinzler
Purpose: Dedicated gene signatures in small (SD-iCCA) and large (LD-iCCA) duct type intrahepatic cholangiocarcinoma remain unknown. We performed immune profiling in SD- and LD-iCCA to identify novel biomarker candidates for personalized medicine.
Methods: Retrospectively, 19 iCCA patients with either SD-iCCA (n = 10, median age, 63.1 years (45-86); men, 4) or LD-iCCA (n = 9, median age, 69.7 years (62-85); men, 5)) were included. All patients were diagnosed and histologically confirmed between 04/2009 and 01/2021. Tumor tissue samples were processed for differential expression profiling using NanoString nCounter® PanCancer Immune Profiling Panel.
Results: With the exception of complement signatures, immune-related pathways were broadly downregulated in SD-iCCA vs. LD-iCCA. A total of 20 immune-related genes were strongly downregulated in SD-iCCA with DMBT1 (log2fc = -5.39, p = 0.01) and CEACAM6 (log2fc = -6.38, p = 0.01) showing the strongest downregulation. Among 7 strongly (log2fc > 2, p ≤ 0.02) upregulated genes, CRP (log2fc = 5.06, p = 0.02) ranked first, and four others were associated with complement (C5, C4BPA, C8A, C8B). Total tumor-infiltrating lymphocytes (TIL) signature was decreased in SD-iCCA with elevated ratios of exhausted-CD8/TILs, NK/TILs, and cytotoxic cells/TILs while having decreased ratios of B-cells/TILs, mast cells/TILs and dendritic cells/TILs. The immune profiling signatures in SD-iCCA revealed downregulation in chemokine signaling pathways inclulding JAK2/3 and ERK1/2 as well as nearly all cytokine-cytokine receptor interaction pathways with the exception of the CXCL1/CXCR1-axis.
Conclusion: Immune patterns differed in SD-iCCA versus LD-iCCA. We identified potential biomarker candidate genes, including CRP, CEACAM6, DMBT1, and various complement factors that could be explored for augmented diagnostics and treatment decision-making.
{"title":"Small duct and large duct type intrahepatic cholangiocarcinoma reveal distinct patterns of immune signatures.","authors":"Simon Bernatz, Falko Schulze, Julia Bein, Katrin Bankov, Scherwin Mahmoudi, Leon D Grünewald, Vitali Koch, Angelika Stehle, Andreas A Schnitzbauer, Dirk Walter, Fabian Finkelmeier, Stefan Zeuzem, Thomas J Vogl, Peter J Wild, Maximilian N Kinzler","doi":"10.1007/s00432-024-05888-y","DOIUrl":"10.1007/s00432-024-05888-y","url":null,"abstract":"<p><strong>Purpose: </strong>Dedicated gene signatures in small (SD-iCCA) and large (LD-iCCA) duct type intrahepatic cholangiocarcinoma remain unknown. We performed immune profiling in SD- and LD-iCCA to identify novel biomarker candidates for personalized medicine.</p><p><strong>Methods: </strong>Retrospectively, 19 iCCA patients with either SD-iCCA (n = 10, median age, 63.1 years (45-86); men, 4) or LD-iCCA (n = 9, median age, 69.7 years (62-85); men, 5)) were included. All patients were diagnosed and histologically confirmed between 04/2009 and 01/2021. Tumor tissue samples were processed for differential expression profiling using NanoString nCounter® PanCancer Immune Profiling Panel.</p><p><strong>Results: </strong>With the exception of complement signatures, immune-related pathways were broadly downregulated in SD-iCCA vs. LD-iCCA. A total of 20 immune-related genes were strongly downregulated in SD-iCCA with DMBT1 (log2fc = -5.39, p = 0.01) and CEACAM6 (log2fc = -6.38, p = 0.01) showing the strongest downregulation. Among 7 strongly (log2fc > 2, p ≤ 0.02) upregulated genes, CRP (log2fc = 5.06, p = 0.02) ranked first, and four others were associated with complement (C5, C4BPA, C8A, C8B). Total tumor-infiltrating lymphocytes (TIL) signature was decreased in SD-iCCA with elevated ratios of exhausted-CD8/TILs, NK/TILs, and cytotoxic cells/TILs while having decreased ratios of B-cells/TILs, mast cells/TILs and dendritic cells/TILs. The immune profiling signatures in SD-iCCA revealed downregulation in chemokine signaling pathways inclulding JAK2/3 and ERK1/2 as well as nearly all cytokine-cytokine receptor interaction pathways with the exception of the CXCL1/CXCR1-axis.</p><p><strong>Conclusion: </strong>Immune patterns differed in SD-iCCA versus LD-iCCA. We identified potential biomarker candidate genes, including CRP, CEACAM6, DMBT1, and various complement factors that could be explored for augmented diagnostics and treatment decision-making.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Neoadjuvant chemotherapy serves as an effective strategy for treating osteosarcoma (OS) not only by targeting cancerous cells but also by influencing the tumor's immune and stromal elements. Gaining insights into how chemotherapy reshapes the tumor's local environment is crucial for advancing OS treatment protocols.
Methods: Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy.
Results: The results revealed that chemotherapy caused the remaining OS cells to express higher levels of genes associated with stemness. Additionally, this process enhances the presence of cancer-associated fibroblasts, increasing their ability to modify the extracellular matrix (ECM). Chemotherapy also increases the number of endothelial cells, albeit with compromised differentiation capabilities. Importantly, the treatment reduced the immune cell population, including myeloid and T/NK cells, particularly impacting the subpopulations with tumor-fighting capabilities.
Conclusion: These findings highlight the complex reaction of the tumor environment to chemotherapy, providing valuable insights into how chemotherapy influences OS cells and the tumor microenvironment (TME). This knowledge is essential for understanding OS resistance mechanisms to treatments, potentially guiding the development of novel therapies for managing advanced OS.
{"title":"Single-cell transcriptomic insights into chemotherapy-induced remodeling of the osteosarcoma tumor microenvironment.","authors":"Xuejing Zheng, Wence Wu, Zhenguo Zhao, Xinxin Zhang, Shengji Yu","doi":"10.1007/s00432-024-05787-2","DOIUrl":"10.1007/s00432-024-05787-2","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant chemotherapy serves as an effective strategy for treating osteosarcoma (OS) not only by targeting cancerous cells but also by influencing the tumor's immune and stromal elements. Gaining insights into how chemotherapy reshapes the tumor's local environment is crucial for advancing OS treatment protocols.</p><p><strong>Methods: </strong>Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy.</p><p><strong>Results: </strong>The results revealed that chemotherapy caused the remaining OS cells to express higher levels of genes associated with stemness. Additionally, this process enhances the presence of cancer-associated fibroblasts, increasing their ability to modify the extracellular matrix (ECM). Chemotherapy also increases the number of endothelial cells, albeit with compromised differentiation capabilities. Importantly, the treatment reduced the immune cell population, including myeloid and T/NK cells, particularly impacting the subpopulations with tumor-fighting capabilities.</p><p><strong>Conclusion: </strong>These findings highlight the complex reaction of the tumor environment to chemotherapy, providing valuable insights into how chemotherapy influences OS cells and the tumor microenvironment (TME). This knowledge is essential for understanding OS resistance mechanisms to treatments, potentially guiding the development of novel therapies for managing advanced OS.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-20DOI: 10.1007/s00432-024-05882-4
Ioannis Fotopoulos, Olav Toai Duc Nguyen, Therese Haugdahl Nøst, Maria Markaki, Vincenzo Lagani, Robin Mjelle, Torkjel Manning Sandanger, Pål Sætrom, Ioannis Tsamardinos, Oluf Dimitri Røe
Introduction: Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis.
Methods: Serum samples from 98,737 subjects from two prospective population studies, HUNT2 and HUNT3, were considered initially. Inclusion criteria for cases were: ever-smokers; no known cancer at study entrance; 0-8 years from blood sampling to LC diagnosis. Each future LC case had one control matched to sex, age at study entrance, pack-years, smoking cessation time, and similar HUNT Lung Cancer Model risk score. A total of 240 and 72 serum samples were included in the discovery (HUNT2) and validation (HUNT3) datasets, respectively, and analysed by next-generation sequencing. The validated serum microRNAs were also tested in two pre-diagnostic plasma datasets from the prospective population studies NOWAC (n = 266) and NSHDS (n = 258). A new model adding clinical variables was also developed and validated.
Results: Fifteen unique microRNAs were discovered and validated in the pre-diagnostic serum datasets when all cases were contrasted against all controls, all with AUC > 0.60. In combination as a 15-microRNAs signature, the AUC reached 0.708 (discovery) and 0.703 (validation). A non-small cell lung cancer signature of six microRNAs showed AUC 0.777 (discovery) and 0.806 (validation). Combined with clinical variables of the HUNT Lung Cancer Model (age, gender, pack-years, daily cough parts of the year, hours of indoor smoke exposure, quit time in years, number of cigarettes daily, body mass index (BMI)) the AUC reached 0.790 (discovery) and 0.833 (validation). These results could not be validated in the plasma samples.
Conclusion: There were a few significantly differential expressed microRNAs in serum up to eight years before diagnosis. These promising microRNAs alone, in concert, or combined with clinical variables have the potential to serve as early diagnostic LC biomarkers. Plasma is not suitable for this analysis. Further validation in larger prospective serum datasets is needed.
{"title":"Promising microRNAs in pre-diagnostic serum associated with lung cancer up to eight years before diagnosis: a HUNT study.","authors":"Ioannis Fotopoulos, Olav Toai Duc Nguyen, Therese Haugdahl Nøst, Maria Markaki, Vincenzo Lagani, Robin Mjelle, Torkjel Manning Sandanger, Pål Sætrom, Ioannis Tsamardinos, Oluf Dimitri Røe","doi":"10.1007/s00432-024-05882-4","DOIUrl":"10.1007/s00432-024-05882-4","url":null,"abstract":"<p><strong>Introduction: </strong>Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis.</p><p><strong>Methods: </strong>Serum samples from 98,737 subjects from two prospective population studies, HUNT2 and HUNT3, were considered initially. Inclusion criteria for cases were: ever-smokers; no known cancer at study entrance; 0-8 years from blood sampling to LC diagnosis. Each future LC case had one control matched to sex, age at study entrance, pack-years, smoking cessation time, and similar HUNT Lung Cancer Model risk score. A total of 240 and 72 serum samples were included in the discovery (HUNT2) and validation (HUNT3) datasets, respectively, and analysed by next-generation sequencing. The validated serum microRNAs were also tested in two pre-diagnostic plasma datasets from the prospective population studies NOWAC (n = 266) and NSHDS (n = 258). A new model adding clinical variables was also developed and validated.</p><p><strong>Results: </strong>Fifteen unique microRNAs were discovered and validated in the pre-diagnostic serum datasets when all cases were contrasted against all controls, all with AUC > 0.60. In combination as a 15-microRNAs signature, the AUC reached 0.708 (discovery) and 0.703 (validation). A non-small cell lung cancer signature of six microRNAs showed AUC 0.777 (discovery) and 0.806 (validation). Combined with clinical variables of the HUNT Lung Cancer Model (age, gender, pack-years, daily cough parts of the year, hours of indoor smoke exposure, quit time in years, number of cigarettes daily, body mass index (BMI)) the AUC reached 0.790 (discovery) and 0.833 (validation). These results could not be validated in the plasma samples.</p><p><strong>Conclusion: </strong>There were a few significantly differential expressed microRNAs in serum up to eight years before diagnosis. These promising microRNAs alone, in concert, or combined with clinical variables have the potential to serve as early diagnostic LC biomarkers. Plasma is not suitable for this analysis. Further validation in larger prospective serum datasets is needed.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies.
Methods: Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality.
Results: From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (-) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence.
Conclusion: Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.
背景:自身免疫性疾病(AD)患者罹患癌症的风险通常会增加。然而,AD对接受手术治疗的肝细胞癌(HCC)患者的影响尚不确定。本研究旨在调查 AD 对接受肝切除术的 HCC 患者生存率的潜在影响:方法:从长庚研究数据库中找出接受手术的 HCC 患者,分析和比较有无 AD 的 HCC 患者的生存结果。结果:从2002年到2018年,总共有450名HCC患者接受了肝癌切除术,其中有1/3的患者在术后死亡:2002年至2018年,共有5532名患者因HCC接受了肝切除术。其中,229 名患者被确定为 AD 患者,5303 名患者未被确定为 AD 患者。排除术后30天内死亡的病例后,估计AD(+)组的中位总生存期(OS)为43.8个月,AD(-)组为47.4个月(P = 0.367)。两组的中位肝特异性生存期和无病生存期(DFS)也相当。经过Cox回归多变量分析,AD的存在并未导致更高的全因死亡率、肝脏特异性死亡率或疾病复发风险:我们的研究表明,自身免疫性疾病不会影响接受肝脏切除术的HCC患者的OS和DFS。AD本身并不是术后肿瘤复发的风险因素。因此,无论是否存在AD,符合肝脏切除条件的患者都应考虑接受手术。要验证我们的研究结果,还需要进一步的研究。
{"title":"Does autoimmune disease impair the survival of hepatocellular carcinoma patients undergoing liver resection? A multi-institutional observational study.","authors":"Chao-Wei Lee, Hsing-Yu Chen, Ping-Han Tsai, Wei-Chen Lee, Chih-Chi Wang, Ming-Chin Yu, Chun-Wei Chen, Po-Ting Lin, Bo-Huan Chen, Sheng-Fu Wang, Pei-Mei Chai, Hsin-I Tsai","doi":"10.1007/s00432-024-05885-1","DOIUrl":"10.1007/s00432-024-05885-1","url":null,"abstract":"<p><strong>Background: </strong>Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies.</p><p><strong>Methods: </strong>Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality.</p><p><strong>Results: </strong>From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (-) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence.</p><p><strong>Conclusion: </strong>Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1007/s00432-024-05867-3
Anoop Kallingal, Radosław Krzemieniecki, Natalia Maciejewska, Wioletta Brankiewicz-Kopcińska, Maciej Baginski
This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.
{"title":"TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.","authors":"Anoop Kallingal, Radosław Krzemieniecki, Natalia Maciejewska, Wioletta Brankiewicz-Kopcińska, Maciej Baginski","doi":"10.1007/s00432-024-05867-3","DOIUrl":"10.1007/s00432-024-05867-3","url":null,"abstract":"<p><p>This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1007/s00432-024-05863-7
Sabine Sommerlatte, Helene Hense, Stephan Nadolny, Anna-Lena Kraeft, Celine Lugnier, Jochen Schmitt, Olaf Schoffer, Anke Reinacher-Schick, Jan Schildmann
Purpose: Cancer care in Germany during the COVID-19 pandemic was affected by resource scarcity and the necessity to prioritize medical measures. This study explores ethical criteria for prioritization and their application in cancer practices from the perspective of German oncologists and other experts.
Methods: We conducted fourteen semi-structured interviews with German oncologists between February and July 2021 and fed findings of interviews and additional data on prioritizing cancer care into four structured group discussions, in January and February 2022, with 22 experts from medicine, nursing, law, ethics, health services research and health insurance. Interviews and group discussions were digitally recorded, transcribed verbatim and analyzed using qualitative content analysis.
Results: Narratives of the participants focus on "urgency" as most acceptable criterion for prioritization in cancer care. Patients who are considered curable and those with a high level of suffering, were given a high degree of "urgency." However, further analysis indicates that the "urgency" criterion needs to be further distinguished according to at least three different dimensions: "urgency" to (1) prevent imminent harm to life, (2) prevent future harm to life and (3) alleviate suffering. In addition, "urgency" is modulated by the "success," which can be reached by means of an intervention, and the "likelihood" of reaching that success.
Conclusion: Our analysis indicates that while "urgency" is a well-established criterion, its operationalization in the context of oncology is challenging. We argue that combined conceptual and clinical analyses are necessary for a sound application of the "urgency" criterion to prioritization in cancer care.
{"title":"What does \"urgency\" mean when prioritizing cancer treatment? Results from a qualitative study with German oncologists and other experts during the COVID-19 pandemic.","authors":"Sabine Sommerlatte, Helene Hense, Stephan Nadolny, Anna-Lena Kraeft, Celine Lugnier, Jochen Schmitt, Olaf Schoffer, Anke Reinacher-Schick, Jan Schildmann","doi":"10.1007/s00432-024-05863-7","DOIUrl":"10.1007/s00432-024-05863-7","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer care in Germany during the COVID-19 pandemic was affected by resource scarcity and the necessity to prioritize medical measures. This study explores ethical criteria for prioritization and their application in cancer practices from the perspective of German oncologists and other experts.</p><p><strong>Methods: </strong>We conducted fourteen semi-structured interviews with German oncologists between February and July 2021 and fed findings of interviews and additional data on prioritizing cancer care into four structured group discussions, in January and February 2022, with 22 experts from medicine, nursing, law, ethics, health services research and health insurance. Interviews and group discussions were digitally recorded, transcribed verbatim and analyzed using qualitative content analysis.</p><p><strong>Results: </strong>Narratives of the participants focus on \"urgency\" as most acceptable criterion for prioritization in cancer care. Patients who are considered curable and those with a high level of suffering, were given a high degree of \"urgency.\" However, further analysis indicates that the \"urgency\" criterion needs to be further distinguished according to at least three different dimensions: \"urgency\" to (1) prevent imminent harm to life, (2) prevent future harm to life and (3) alleviate suffering. In addition, \"urgency\" is modulated by the \"success,\" which can be reached by means of an intervention, and the \"likelihood\" of reaching that success.</p><p><strong>Conclusion: </strong>Our analysis indicates that while \"urgency\" is a well-established criterion, its operationalization in the context of oncology is challenging. We argue that combined conceptual and clinical analyses are necessary for a sound application of the \"urgency\" criterion to prioritization in cancer care.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-13DOI: 10.1007/s00432-024-05877-1
Baoyang Luo, Lin Zhuang, Ju Huang, Longqing Shi, Li Zhang, Maoqun Zhu, Yunjie Lu, Qiang Zhu, Donglin Sun, Hao Wang, Haisheng Fang
Purpose: Long noncoding RNAs (lncRNAs) exert a significant influence on various cancer-related processes through their intricate interactions with RNAs. Among these, lncRNA ZFAS1 has been implicated in oncogenic roles in multiple cancer types. Nevertheless, the intricate biological significance and underlying mechanism of ZFAS1 in the initiation and progression of hepatocellular carcinoma (HCC) remain largely unexplored.
Methods: Analysis of The Cancer Genome Atlas Program (TCGA) database revealed a notable upregulation of lncRNA ZFAS1 in HCC tissues. To explore its function, we investigated colony formation and performed CCK-8 assays to gauge cellular proliferation and wound healing, Transwell assays to assess cellular migration, and an in vivo study employing a nude mouse model to scrutinize tumor growth and metastasis. Luciferase reporter assay was used to confirm the implicated interactions. Rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC.
Results: ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. We observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration. SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo.
Conclusion: Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.
{"title":"LncRNA ZFAS1 regulates ATIC transcription and promotes the proliferation and migration of hepatocellular carcinoma through the PI3K/AKT signaling pathway.","authors":"Baoyang Luo, Lin Zhuang, Ju Huang, Longqing Shi, Li Zhang, Maoqun Zhu, Yunjie Lu, Qiang Zhu, Donglin Sun, Hao Wang, Haisheng Fang","doi":"10.1007/s00432-024-05877-1","DOIUrl":"10.1007/s00432-024-05877-1","url":null,"abstract":"<p><strong>Purpose: </strong>Long noncoding RNAs (lncRNAs) exert a significant influence on various cancer-related processes through their intricate interactions with RNAs. Among these, lncRNA ZFAS1 has been implicated in oncogenic roles in multiple cancer types. Nevertheless, the intricate biological significance and underlying mechanism of ZFAS1 in the initiation and progression of hepatocellular carcinoma (HCC) remain largely unexplored.</p><p><strong>Methods: </strong>Analysis of The Cancer Genome Atlas Program (TCGA) database revealed a notable upregulation of lncRNA ZFAS1 in HCC tissues. To explore its function, we investigated colony formation and performed CCK-8 assays to gauge cellular proliferation and wound healing, Transwell assays to assess cellular migration, and an in vivo study employing a nude mouse model to scrutinize tumor growth and metastasis. Luciferase reporter assay was used to confirm the implicated interactions. Rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC.</p><p><strong>Results: </strong>ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. We observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration. SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo.</p><p><strong>Conclusion: </strong>Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-13DOI: 10.1007/s00432-024-05884-2
Astrid Bauschke, Annelore Altendorf-Hofmann, Aladdin Ali-Deeb, Michael Ardelt, Felix Dondorf, Falk Rauchfuss, Oliver Rohland, Aysun Tekbaș, Utz Settmacher
Purpose: The biology of rare pancreatic tumours, which differs from that of ductal pancreatic cancer, requires increased attention. Although the majority of rare pancreatic tumours are benign, it is difficult to decide whether an invasive component exists without complete removal of the lesion, despite considerable progress in diagnosis. We are investigating a large cohort of patients with histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas.
Methods: Here we analyze long-term survival from patients, who underwent resection of histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas. At our department between Jan 1st, 1999, and Dec 31st, 2019. The median follow-up was 61 (range 0-168) month. All statistical analyses were performed using SPSS 26.0 (IBM, Chicago, IL, USA) software.
Results: 46 patients (48%) were followed up for more than 5 years, 18 patients (19%) for more than 10 years. The 5-year and 10-year survival rates for rare non-invasive pancreatic tumours were 72% and 55% respectively. The proportion of rare tumour entities (non-ductal and non-neuroendocrine) increased continuously and statistically significantly (p = 0.004) from 4.2 to 12.3% in our clinic between 1999 and 2019. If there is no invasive growth yet, there is a varying risk of malignant degeneration in the course of the disease. Therefore, the indication for pancreatic resection is still the subject of discussion.
Conclusion: The long-term prognosis of rare epithelial pancreatic tumours after R0 resection-even if they are already malignant-is much better than that of ductal pancreatic cancer.
{"title":"Rare tumours of the pancreas: monocentric study.","authors":"Astrid Bauschke, Annelore Altendorf-Hofmann, Aladdin Ali-Deeb, Michael Ardelt, Felix Dondorf, Falk Rauchfuss, Oliver Rohland, Aysun Tekbaș, Utz Settmacher","doi":"10.1007/s00432-024-05884-2","DOIUrl":"10.1007/s00432-024-05884-2","url":null,"abstract":"<p><strong>Purpose: </strong>The biology of rare pancreatic tumours, which differs from that of ductal pancreatic cancer, requires increased attention. Although the majority of rare pancreatic tumours are benign, it is difficult to decide whether an invasive component exists without complete removal of the lesion, despite considerable progress in diagnosis. We are investigating a large cohort of patients with histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas.</p><p><strong>Methods: </strong>Here we analyze long-term survival from patients, who underwent resection of histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas. At our department between Jan 1st, 1999, and Dec 31st, 2019. The median follow-up was 61 (range 0-168) month. All statistical analyses were performed using SPSS 26.0 (IBM, Chicago, IL, USA) software.</p><p><strong>Results: </strong>46 patients (48%) were followed up for more than 5 years, 18 patients (19%) for more than 10 years. The 5-year and 10-year survival rates for rare non-invasive pancreatic tumours were 72% and 55% respectively. The proportion of rare tumour entities (non-ductal and non-neuroendocrine) increased continuously and statistically significantly (p = 0.004) from 4.2 to 12.3% in our clinic between 1999 and 2019. If there is no invasive growth yet, there is a varying risk of malignant degeneration in the course of the disease. Therefore, the indication for pancreatic resection is still the subject of discussion.</p><p><strong>Conclusion: </strong>The long-term prognosis of rare epithelial pancreatic tumours after R0 resection-even if they are already malignant-is much better than that of ductal pancreatic cancer.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}