Sofia Laila Wik, Wenxin Tian, Claire Chenwen Zhong, Apurva Sawhney, Mingjun Gao, Qinyao Yu, Fanyu Xue, Sze Chai Chan, Shui Hang Chow, Yusuff Adebayo Adebisi, Jinqiu Yuan, Don Eliseo Lucero-Prisno III, Martin C. S. Wong, Junjie Huang, Global Health Focus Epidemiology Group (GHFEG)
Background
Globally, pancreatic cancer poses a significant concern for public health.
Aims
The objective of this study was to assess the burden of pancreatic cancer on varying income levels.
Methods and Results
Data from the Global Burden of Disease Study (GBD) 2021 and Gross Domestic Product Per Capita data were utilised in this study. All countries were categorised into four groups based on their income levels. Age-standardised incidence, mortality and disability-adjusted life years (DALYs) rates were the primary parameters to analyse the burden of pancreatic cancer. The associations between pancreatic cancer burden and countries' economic levels were analysed with linear regression models. High-income-level countries generally had a higher burden compared to other income levels in 2021. Greenland had the highest rate of age-standardised DALYs at 374.93 per 100 000, followed by Uruguay (297.06) and Monaco (290.87). A higher gross domestic product (GDP) per capita was linked to a higher age-standardised incidence (β = 0.77, 95% CI = 0.63, 0.90, p < 0.001), mortality (β = 0.72, 95% CI = 0.59, 0.86, p < 0.001) and DALYs (β = 14.59, 95% CI = 11.38, 17.80, p < 0.001). From 1990 to 2021, the pancreatic cancer burden increased across all income levels, with the most pronounced rise seen in lower-middle-income countries. Smoking-related age-standardised DALYs have decreased since 1990. However, there was a notable increase in males in upper-middle-income countries during the same period.
Conclusion
In conclusion, the pancreatic cancer burden has been increasing globally. The burden of pancreatic cancer varies significantly among countries with different income levels. Effective preventions are needed to control the burden of pancreatic cancer.
{"title":"Distribution, Risk Factors and Epidemiological Trends of Pancreatic Cancer Across Countries’ Income Levels: A Comprehensive Analysis","authors":"Sofia Laila Wik, Wenxin Tian, Claire Chenwen Zhong, Apurva Sawhney, Mingjun Gao, Qinyao Yu, Fanyu Xue, Sze Chai Chan, Shui Hang Chow, Yusuff Adebayo Adebisi, Jinqiu Yuan, Don Eliseo Lucero-Prisno III, Martin C. S. Wong, Junjie Huang, Global Health Focus Epidemiology Group (GHFEG)","doi":"10.1002/cnr2.70154","DOIUrl":"https://doi.org/10.1002/cnr2.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Globally, pancreatic cancer poses a significant concern for public health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The objective of this study was to assess the burden of pancreatic cancer on varying income levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Data from the Global Burden of Disease Study (GBD) 2021 and Gross Domestic Product Per Capita data were utilised in this study. All countries were categorised into four groups based on their income levels. Age-standardised incidence, mortality and disability-adjusted life years (DALYs) rates were the primary parameters to analyse the burden of pancreatic cancer. The associations between pancreatic cancer burden and countries' economic levels were analysed with linear regression models. High-income-level countries generally had a higher burden compared to other income levels in 2021. Greenland had the highest rate of age-standardised DALYs at 374.93 per 100 000, followed by Uruguay (297.06) and Monaco (290.87). A higher gross domestic product (GDP) per capita was linked to a higher age-standardised incidence (β = 0.77, 95% CI = 0.63, 0.90, <i>p</i> < 0.001), mortality (β = 0.72, 95% CI = 0.59, 0.86, <i>p</i> < 0.001) and DALYs (β = 14.59, 95% CI = 11.38, 17.80, <i>p</i> < 0.001). From 1990 to 2021, the pancreatic cancer burden increased across all income levels, with the most pronounced rise seen in lower-middle-income countries. Smoking-related age-standardised DALYs have decreased since 1990. However, there was a notable increase in males in upper-middle-income countries during the same period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, the pancreatic cancer burden has been increasing globally. The burden of pancreatic cancer varies significantly among countries with different income levels. Effective preventions are needed to control the burden of pancreatic cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glycoprotein M6A (GPM6A) encodes a transmembrane protein, expressing in large quantities on the cell surface of central nervous system (CNS) neurons. GPM6A acts importantly in neurodevelopment by modulating neuronal differentiation, migration, axon growth, synaptogenesis, and spine formation, but its role in malignancy remains controversial and requires further research. This article reviewed the mechanisms of GPM6A in colorectal cancer, liver cancer, lung cancer, glioblastoma, and other malignant tumors, and made a “one-stop” summary of the relevant mechanisms.
Recent Findings
Researches have indicated that GPM6A is related to malignant tumors. It affects epithelial-mesenchymal transition and induces the formation of filopodia, participating in the adhesion, migration, and metastasis of cancer cells. Its role in malignant tumors remains controversial, however. On the one hand, GPM6A may have carcinogenic properties and is related to poor prognosis of malignant tumors. It is highly expressed in lymphoblastic leukemia and is a potential oncogene. It also shows carcinogenic properties in colorectal cancer, glioblastoma, gonadotroph adenomas and so on. On the other hand, the expression of GPM6A decreases in lung adenocarcinoma, liver cancer, thyroid cancer, and so forth as the tumor progresses, and it can inhibit the progression of malignant tumors by inhibiting some signaling pathways, suggesting that it may be a tumor suppressor gene.
Conclusion
Carcinogenic or tumor suppressive? Although the biological function of GPM6A in the development of malignant tumors is still unclear, according to the current research progress, it is still expected to become an effective molecular marker for predicting tumor occurrence, metastasis and prognosis, as well as a new target for diagnosis and treatment.
{"title":"Mechanisms of GPM6A in Malignant Tumors","authors":"Bei Huang, Xihong Li","doi":"10.1002/cnr2.70137","DOIUrl":"https://doi.org/10.1002/cnr2.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glycoprotein M6A (GPM6A) encodes a transmembrane protein, expressing in large quantities on the cell surface of central nervous system (CNS) neurons. GPM6A acts importantly in neurodevelopment by modulating neuronal differentiation, migration, axon growth, synaptogenesis, and spine formation, but its role in malignancy remains controversial and requires further research. This article reviewed the mechanisms of GPM6A in colorectal cancer, liver cancer, lung cancer, glioblastoma, and other malignant tumors, and made a “one-stop” summary of the relevant mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent Findings</h3>\u0000 \u0000 <p>Researches have indicated that GPM6A is related to malignant tumors. It affects epithelial-mesenchymal transition and induces the formation of filopodia, participating in the adhesion, migration, and metastasis of cancer cells. Its role in malignant tumors remains controversial, however. On the one hand, GPM6A may have carcinogenic properties and is related to poor prognosis of malignant tumors. It is highly expressed in lymphoblastic leukemia and is a potential oncogene. It also shows carcinogenic properties in colorectal cancer, glioblastoma, gonadotroph adenomas and so on. On the other hand, the expression of GPM6A decreases in lung adenocarcinoma, liver cancer, thyroid cancer, and so forth as the tumor progresses, and it can inhibit the progression of malignant tumors by inhibiting some signaling pathways, suggesting that it may be a tumor suppressor gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Carcinogenic or tumor suppressive? Although the biological function of GPM6A in the development of malignant tumors is still unclear, according to the current research progress, it is still expected to become an effective molecular marker for predicting tumor occurrence, metastasis and prognosis, as well as a new target for diagnosis and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. H. A. Saler, S. Shuai, J. C. Beckervordersandforth, D. Rennspiess, G. Roemen, T. Gevers, M. C. F. Stoehr-Kleinegris, S. A. W. Bouwense, M. J. L. Dewulf, M. M. E. Coolsen, M. H. A. Bemelmans, S. W. Olde Damink, V. Winnepenninckx, A. zur Hausen, M. Kramer, I. V. Samarska
Aim
We aimed to analyze hepatocellular carcinoma (HCC) morphological subtypes characterized according to the WHO classification and the International Collaboration on Cancer Reporting (ICCR) recommendations, and their prognostic features in a Dutch population.
Methods and Results
This retrospective study in a tertiary referral center included the histopathological revision of 62 HCC resection specimens, obtained from 22 female and 40 male patients (median age: 67 years), in a period between 2011 and 2021 at the Maastricht University Medical Center +. Clinical data, morphological subtypes, growth pattern (GP), tumor grade, tumor extension, margins, and vascular and perineural invasion were collected. Eighteen cases were assigned a specific morphologic subtype and steatohepatic HCC was the most common in our cohort. Twenty-one tumors classified as conventional type HCC (HCC-NOS), commonly exhibiting two concurrent GPs. Twenty-three cases revealed a heterogeneous morphologic differentiation, compromising the combination of HCC-NOS with another morphologic subtype, most frequently a steatohepatitic component. Comparison of HCC-NOS and HCC with heterogeneous morphology did not show significant differences in the main clinicopathological characteristics and survival.
Conclusion
Although the most common morphologic subtype was steatohepatitic HCC, the majority of cases demonstrated multiple morphologic patterns. In case of HCC-NOS, heterogeneous GPs were often observed. Therefore, a histomorphological diagnosis based on a single tumor biopsy specimen may lead to incorrect classification of HCC. Sufficient tumor sampling of HCC resection specimens is required for the complete evaluation of all histomorphological features followed by correct subclassification in order to meet the clinical needs regarding prognostic relevance and patient follow-up.
{"title":"Clinicopathological Study on Morphological Subtypes of Hepatocellular Carcinoma: A Single Tertiary Referral Center Experience","authors":"C. H. A. Saler, S. Shuai, J. C. Beckervordersandforth, D. Rennspiess, G. Roemen, T. Gevers, M. C. F. Stoehr-Kleinegris, S. A. W. Bouwense, M. J. L. Dewulf, M. M. E. Coolsen, M. H. A. Bemelmans, S. W. Olde Damink, V. Winnepenninckx, A. zur Hausen, M. Kramer, I. V. Samarska","doi":"10.1002/cnr2.70127","DOIUrl":"https://doi.org/10.1002/cnr2.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to analyze hepatocellular carcinoma (HCC) morphological subtypes characterized according to the WHO classification and the International Collaboration on Cancer Reporting (ICCR) recommendations, and their prognostic features in a Dutch population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>This retrospective study in a tertiary referral center included the histopathological revision of 62 HCC resection specimens, obtained from 22 female and 40 male patients (median age: 67 years), in a period between 2011 and 2021 at the Maastricht University Medical Center +. Clinical data, morphological subtypes, growth pattern (GP), tumor grade, tumor extension, margins, and vascular and perineural invasion were collected. Eighteen cases were assigned a specific morphologic subtype and steatohepatic HCC was the most common in our cohort. Twenty-one tumors classified as conventional type HCC (HCC-NOS), commonly exhibiting two concurrent GPs. Twenty-three cases revealed a heterogeneous morphologic differentiation, compromising the combination of HCC-NOS with another morphologic subtype, most frequently a steatohepatitic component. Comparison of HCC-NOS and HCC with heterogeneous morphology did not show significant differences in the main clinicopathological characteristics and survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although the most common morphologic subtype was steatohepatitic HCC, the majority of cases demonstrated multiple morphologic patterns. In case of HCC-NOS, heterogeneous GPs were often observed. Therefore, a histomorphological diagnosis based on a single tumor biopsy specimen may lead to incorrect classification of HCC. Sufficient tumor sampling of HCC resection specimens is required for the complete evaluation of all histomorphological features followed by correct subclassification in order to meet the clinical needs regarding prognostic relevance and patient follow-up.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rita Szodorai, Emőke Fülöp, Andrei Fülöp, Radu Mircea Neagoe, Simona Gurzu
Background
Synchronous occurrence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is extremely rare.
Case
A 67-year-old male was admitted to the hospital with hemoperitoneum caused by a liver mass rupture and elevated serum liver enzymes. Abdominal magnetic resonance imaging revealed a solid mass, with 38 mm in maximum diameter, located in the fifth/sixth segments of the liver, suggesting an HCC. Emergency surgery was performed and a second liver mass in the fourth segment was identified intraoperatively, with 20 mm in maximum diameter. Hepatic resection of the affected segments was performed with free resection margins. Histopathological examination revealed the synchronous occurrence of HCC and ICC with a predominant ductal plate malformation pattern. The patient is still alive at 41 months after its first surgery.
Conclusions
In patients with HCC, a proper intraoperative assessment is indicated, in addition to imaging investigations, to detect synchronous lesions that can change the therapeutic approach. This is the first case ever reported in the literature in which synchronous HCC and ICC with a predominant ductal plate malformation pattern were incidentally diagnosed in a patient with hemoperitoneum.
{"title":"Synchronous Hepatocellular and Intrahepatic Cholangiocellular Carcinoma With Predominant Ductal Plate Malformation Pattern. A Case Report and Review of the Literature","authors":"Rita Szodorai, Emőke Fülöp, Andrei Fülöp, Radu Mircea Neagoe, Simona Gurzu","doi":"10.1002/cnr2.70085","DOIUrl":"https://doi.org/10.1002/cnr2.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Synchronous occurrence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is extremely rare.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>A 67-year-old male was admitted to the hospital with hemoperitoneum caused by a liver mass rupture and elevated serum liver enzymes. Abdominal magnetic resonance imaging revealed a solid mass, with 38 mm in maximum diameter, located in the fifth/sixth segments of the liver, suggesting an HCC. Emergency surgery was performed and a second liver mass in the fourth segment was identified intraoperatively, with 20 mm in maximum diameter. Hepatic resection of the affected segments was performed with free resection margins. Histopathological examination revealed the synchronous occurrence of HCC and ICC with a predominant ductal plate malformation pattern. The patient is still alive at 41 months after its first surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with HCC, a proper intraoperative assessment is indicated, in addition to imaging investigations, to detect synchronous lesions that can change the therapeutic approach. This is the first case ever reported in the literature in which synchronous HCC and ICC with a predominant ductal plate malformation pattern were incidentally diagnosed in a patient with hemoperitoneum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margaret Raber, Brad Love, Maria Vazquez, Charulata Ghosh, Ruth Rechis, Katherine Oestman, Thy Ho-Pham, Denise LaRue, Michael T. Walsh, Darya Kizub, Hilary Ma, Karen Basen-Engquist
Objective
The objective of this paper was to qualitatively explore the eating habits and experience of nutrition security during cancer treatment among patients from an area of persistent poverty being treated in a safety net hospital oncology program.
Methods
Eleven in-depth interviews were conducted with current individuals with cancer who were (1) undergoing active cancer treatment at LBJ Hospital, (2) over 18 years old, (3) English speaking, and (4) residing in an Acres Homes zip code. Reflexive thematic analysis was undertaken by four members of the study team, which brought together diverse expertise in health disparities, nutrition, food culture, and health communication.
Results
Four main themes emerged from the data, including (1) food beliefs and eating behaviors in the context of cancer, (2) social and economic influences on food selection, procurement, and preparation, (3) lived experience of resiliency and coping with limited resources, and (4) the role of relationships (including social support, family, medical teams) in diet and food choice.
Conclusion
Findings from this study begin to fill a gap in knowledge regarding the complexities of managing nutritional needs among patients residing in an area of persistent poverty, which can inform the development of future health systems and community-based resources for those negotiating both cancer and chronically limited resources.
{"title":"Nutrition Security During Cancer: A Qualitative Investigation Among Patients With Cancer on Active Treatment From an Area of Persistent Poverty","authors":"Margaret Raber, Brad Love, Maria Vazquez, Charulata Ghosh, Ruth Rechis, Katherine Oestman, Thy Ho-Pham, Denise LaRue, Michael T. Walsh, Darya Kizub, Hilary Ma, Karen Basen-Engquist","doi":"10.1002/cnr2.70141","DOIUrl":"https://doi.org/10.1002/cnr2.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this paper was to qualitatively explore the eating habits and experience of nutrition security during cancer treatment among patients from an area of persistent poverty being treated in a safety net hospital oncology program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eleven in-depth interviews were conducted with current individuals with cancer who were (1) undergoing active cancer treatment at LBJ Hospital, (2) over 18 years old, (3) English speaking, and (4) residing in an Acres Homes zip code. Reflexive thematic analysis was undertaken by four members of the study team, which brought together diverse expertise in health disparities, nutrition, food culture, and health communication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four main themes emerged from the data, including (1) food beliefs and eating behaviors in the context of cancer, (2) social and economic influences on food selection, procurement, and preparation, (3) lived experience of resiliency and coping with limited resources, and (4) the role of relationships (including social support, family, medical teams) in diet and food choice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Findings from this study begin to fill a gap in knowledge regarding the complexities of managing nutritional needs among patients residing in an area of persistent poverty, which can inform the development of future health systems and community-based resources for those negotiating both cancer and chronically limited resources.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chengyuan Li, Yucheng Xue, Eloy Yinwang, Zhaoming Ye
Background
MDSCs are immature neutrophils and monocytes with immunosuppressive potentials, involving mononuclear MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs).
Recent Findings
They are significant components of the tumor microenvironment (TME). Besides, recent studies also verified that MDSCs also facilitated the progression of bone metastasis by regulating the network of cytokines and the function of immune cells.
Conclusion
It is necessary to summarize the mechanisms of MDSC recruitment and immunosuppression, and their impact on bone metastasis.
{"title":"The Recruitment and Immune Suppression Mechanisms of Myeloid-Derived Suppressor Cells and Their Impact on Bone Metastatic Cancer","authors":"Chengyuan Li, Yucheng Xue, Eloy Yinwang, Zhaoming Ye","doi":"10.1002/cnr2.70044","DOIUrl":"https://doi.org/10.1002/cnr2.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>MDSCs are immature neutrophils and monocytes with immunosuppressive potentials, involving mononuclear MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent Findings</h3>\u0000 \u0000 <p>They are significant components of the tumor microenvironment (TME). Besides, recent studies also verified that MDSCs also facilitated the progression of bone metastasis by regulating the network of cytokines and the function of immune cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It is necessary to summarize the mechanisms of MDSC recruitment and immunosuppression, and their impact on bone metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The emergence of constitutively active androgen receptor (AR) splice variant AR-V7 poses a formidable challenge in treating prostate cancer, as it lacks the ligand binding region targeted by androgen-deprivation therapies such as enzalutamide and abiraterone. AR-V7 is critical for castration-resistant prostate cancer (CRPC) development and progression; however, the molecular mechanisms regulating its expression and biological function remain poorly understood. Here, we investigate the role of IGF2BP2 in regulating AR-V7 expression and CRPC progression.
Methods
To determine the clinical relevance of IGF2BP2 in CRPC, we analyzed the mRNA expression data for prostate cancer patients available in the Genomic Data Commons (GDC) Data Portal and cBioPortal. Next to investigate the role of IGF2BP2 in regulating AR-V7 expression and enzalutamide resistance, we performed shRNA-mediated IGF2BP2 knockdown and overexpression experiments followed by qRT-PCR, immunoblot, colony-formation, and MTT assays. Finally, we performed RIP-qPCR, actinomycin-D, and IGF2BP2 domain-deletion analysis to study the mechanism by which IGF2BP2 regulates AR-V7 stability, expression, and enzalutamide resistance in CRPC cells.
Results
Our analysis revealed that IGF2BP2 is upregulated in CRPC patients and its expression positively correlates with increasing Gleason score in patients with CRPC. We demonstrate that IGF2BP2 silencing leads to downregulation of AR-V7 and its downstream target genes without affecting AR levels. Additionally, IGF2BP2 knockdown also enhances the sensitivity of CRPC cells to enzalutamide while overexpression increases AR-V7 expression and confers increased resistance to enzalutamide. Mechanistically, our experiments demonstrate that IGF2BP2 binds to the intronic splicing enhancer (ISE) region of AR-V7, thereby enhancing its mRNA stability. Furthermore, our domain-deletion analysis pinpoints the role of KH3 and KH4 domains of IGF2BP2 in regulating AR-V7 stability and enzalutamide resistance.
Conclusions
Taken together, our findings suggest that IGF2BP2 plays a critical role in regulating AR-V7 expression and stability, offering a novel target for developing therapeutic interventions for CRPC.
{"title":"Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2) Promotes Castration-Resistant Prostate Cancer Progression by Regulating AR-V7 mRNA Stability","authors":"Taruna Saini, Devesh Srivastava, Rajnikant Raut, Parul Mishra, Ashish Misra","doi":"10.1002/cnr2.70096","DOIUrl":"https://doi.org/10.1002/cnr2.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The emergence of constitutively active androgen receptor (AR) splice variant AR-V7 poses a formidable challenge in treating prostate cancer, as it lacks the ligand binding region targeted by androgen-deprivation therapies such as enzalutamide and abiraterone. AR-V7 is critical for castration-resistant prostate cancer (CRPC) development and progression; however, the molecular mechanisms regulating its expression and biological function remain poorly understood. Here, we investigate the role of IGF2BP2 in regulating AR-V7 expression and CRPC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To determine the clinical relevance of IGF2BP2 in CRPC, we analyzed the mRNA expression data for prostate cancer patients available in the Genomic Data Commons (GDC) Data Portal and cBioPortal. Next to investigate the role of IGF2BP2 in regulating AR-V7 expression and enzalutamide resistance, we performed shRNA-mediated IGF2BP2 knockdown and overexpression experiments followed by qRT-PCR, immunoblot, colony-formation, and MTT assays. Finally, we performed RIP-qPCR, actinomycin-D, and IGF2BP2 domain-deletion analysis to study the mechanism by which IGF2BP2 regulates AR-V7 stability, expression, and enzalutamide resistance in CRPC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis revealed that IGF2BP2 is upregulated in CRPC patients and its expression positively correlates with increasing Gleason score in patients with CRPC. We demonstrate that IGF2BP2 silencing leads to downregulation of AR-V7 and its downstream target genes without affecting AR levels. Additionally, IGF2BP2 knockdown also enhances the sensitivity of CRPC cells to enzalutamide while overexpression increases AR-V7 expression and confers increased resistance to enzalutamide. Mechanistically, our experiments demonstrate that IGF2BP2 binds to the intronic splicing enhancer (ISE) region of AR-V7, thereby enhancing its mRNA stability. Furthermore, our domain-deletion analysis pinpoints the role of KH3 and KH4 domains of IGF2BP2 in regulating AR-V7 stability and enzalutamide resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, our findings suggest that IGF2BP2 plays a critical role in regulating AR-V7 expression and stability, offering a novel target for developing therapeutic interventions for CRPC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sakditad Saowapa, Natchaya Polpichai, Pharit Siladech, Chalothorn Wannaphut, Manasawee Tanariyakul, Phuuwadith Wattanachayakul, Diego Olavarria Bernal, Hector Garcia Pleitez, Lukman Tijani
<div> <section> <h3> Background</h3> <p>In recent years, immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced malignancies. As such, numerous ICIs are establishing themselves as prospective therapy alternatives for individuals with head and neck cancer (HNC). Evidence suggests a potential correlation between body mass index (BMI) and the efficacy of ICIs in cancer patients. However, this association in HNC patients subjected to immunotherapy is still unclear.</p> </section> <section> <h3> Aims</h3> <p>To investigate the effect of BMI on the survival outcomes of HNC patients treated with immunotherapy.</p> </section> <section> <h3> Methods</h3> <p>PubMed, Web of Science, and Google Scholar databases were searched extensively for records published until January 2024. Full-text articles aligned with the research objective were included, while records published in English, case reports, reviews, editorials, and studies reporting immunotherapy combined with other cancer therapies were excluded. The data required for review and analysis was abstracted in Excel files by two independent reviewers. Additionally, data synthesis was carried out using the Review Manager program, and evaluation of methodological quality was done with the Newcastle Ottawa scale. The statistical analyses were stratified according to the BMI values, of which patients were categorized as follows: Obese (BMI ≥ 27.5), non-obese (BMI < 27.5), overweight (BMI: 23.5–27.5), underweight (BMI < 18.5), normal (BMI: 18.5–23.5), low (BMI < 20), and high (BMI ≥ 20).</p> </section> <section> <h3> Results</h3> <p>Only six studies were reviewed and analyzed. A subgroup analysis of data from these studies showed that obese HNC patients on immunotherapy had significantly better overall survival (OS) rates than non-obese patients (HR: 0.51; 95% CI: 0.29–0.93; <i>p</i> = 0.03). However, the progression-free survival (PFS) was statistically similar between obese and non-obese patients (HR: 0.72; 95% CI: 0.39–1.33; <i>p</i> = 0.30). In addition, when BMI was stratified as either low or high, no significant difference was observed in the OS and PFS of HNC patients (HR: 0.99; 95% CI: 0.59–1.66; <i>p</i> = 0.97 and HR: 0.93; 95% CI: 0.61–1.41; <i>p</i> = 0.42, respectively). Similarly, the statistical analyses showed that overweight patients have similar OS and PFS as patients with normal BMI (HR: 0.53; 95% CI: 0.15–1.92; <i>p</i> = 0.33 and HR: 0.55; 95% CI: 0.20–1.52; <i>p</i> = 0.25, respectively). In contrast, underweight patients demonstrated p
{"title":"BMI Association With Treatment Outcomes in Head and Neck Cancer Patients Receiving Immunotherapy: A Comprehensive Review and Meta-Analysis","authors":"Sakditad Saowapa, Natchaya Polpichai, Pharit Siladech, Chalothorn Wannaphut, Manasawee Tanariyakul, Phuuwadith Wattanachayakul, Diego Olavarria Bernal, Hector Garcia Pleitez, Lukman Tijani","doi":"10.1002/cnr2.70147","DOIUrl":"https://doi.org/10.1002/cnr2.70147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In recent years, immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced malignancies. As such, numerous ICIs are establishing themselves as prospective therapy alternatives for individuals with head and neck cancer (HNC). Evidence suggests a potential correlation between body mass index (BMI) and the efficacy of ICIs in cancer patients. However, this association in HNC patients subjected to immunotherapy is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the effect of BMI on the survival outcomes of HNC patients treated with immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, Web of Science, and Google Scholar databases were searched extensively for records published until January 2024. Full-text articles aligned with the research objective were included, while records published in English, case reports, reviews, editorials, and studies reporting immunotherapy combined with other cancer therapies were excluded. The data required for review and analysis was abstracted in Excel files by two independent reviewers. Additionally, data synthesis was carried out using the Review Manager program, and evaluation of methodological quality was done with the Newcastle Ottawa scale. The statistical analyses were stratified according to the BMI values, of which patients were categorized as follows: Obese (BMI ≥ 27.5), non-obese (BMI < 27.5), overweight (BMI: 23.5–27.5), underweight (BMI < 18.5), normal (BMI: 18.5–23.5), low (BMI < 20), and high (BMI ≥ 20).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Only six studies were reviewed and analyzed. A subgroup analysis of data from these studies showed that obese HNC patients on immunotherapy had significantly better overall survival (OS) rates than non-obese patients (HR: 0.51; 95% CI: 0.29–0.93; <i>p</i> = 0.03). However, the progression-free survival (PFS) was statistically similar between obese and non-obese patients (HR: 0.72; 95% CI: 0.39–1.33; <i>p</i> = 0.30). In addition, when BMI was stratified as either low or high, no significant difference was observed in the OS and PFS of HNC patients (HR: 0.99; 95% CI: 0.59–1.66; <i>p</i> = 0.97 and HR: 0.93; 95% CI: 0.61–1.41; <i>p</i> = 0.42, respectively). Similarly, the statistical analyses showed that overweight patients have similar OS and PFS as patients with normal BMI (HR: 0.53; 95% CI: 0.15–1.92; <i>p</i> = 0.33 and HR: 0.55; 95% CI: 0.20–1.52; <i>p</i> = 0.25, respectively). In contrast, underweight patients demonstrated p","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viral infections are established contributors to oncogenesis, leading to significant public health challenges. This systematic review aims to synthesize current knowledge on the mechanisms of viral cellular transformation and their association with various cancers.
Recent findings
Studies reveal key mechanisms of oncogenesis, including direct viral integration into the host genome, expression of viral oncogenes, and indirect pathways such as chronic inflammation and immune evasion. Notably, Human Papillomavirus (HPV) was linked predominantly to cervical and oropharyngeal cancers, while Epstein–Barr Virus (EBV) was associated with lymphomas. Hepatitis B and C viruses were linked to liver cancer, highlighting the diverse impacts of viral infections on oncogenic processes.
Conclusions
This review underscores the complexity of viral interactions with host cells and their implications for cancer development. Findings suggest that targeted interventions, such as vaccination and antiviral therapies, may play a crucial role in reducing the incidence of virus-related cancers. Further research is needed to explore novel therapeutic strategies and the role of co-factors in viral oncogenesis.
{"title":"The Role of Viruses in Cellular Transformation and Cancer","authors":"Donath Damian","doi":"10.1002/cnr2.70150","DOIUrl":"https://doi.org/10.1002/cnr2.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Viral infections are established contributors to oncogenesis, leading to significant public health challenges. This systematic review aims to synthesize current knowledge on the mechanisms of viral cellular transformation and their association with various cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent findings</h3>\u0000 \u0000 <p>Studies reveal key mechanisms of oncogenesis, including direct viral integration into the host genome, expression of viral oncogenes, and indirect pathways such as chronic inflammation and immune evasion. Notably, Human Papillomavirus (HPV) was linked predominantly to cervical and oropharyngeal cancers, while Epstein–Barr Virus (EBV) was associated with lymphomas. Hepatitis B and C viruses were linked to liver cancer, highlighting the diverse impacts of viral infections on oncogenic processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review underscores the complexity of viral interactions with host cells and their implications for cancer development. Findings suggest that targeted interventions, such as vaccination and antiviral therapies, may play a crucial role in reducing the incidence of virus-related cancers. Further research is needed to explore novel therapeutic strategies and the role of co-factors in viral oncogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristian M. Hargadon, Travis B. Goodloe III, Stephen L. Woodall II
Background
Lymph node invasion by cancer cells is a poor prognostic factor and is often associated with anti-tumor CD8+ T cell dysfunction. In this study, we investigated the role of lymph node invasion by melanoma cells in the induction of incomplete differentiation by tumor antigen-specific CD8+ T cells.
Aims
We aimed to determine whether lymph node invasion by melanoma cells is required for this specific form of anti-tumor CD8+ T cell dysfunction.
Methods and Results
We assessed lymph node invasion by the B16-F1 and D5.1G4 murine melanoma cell lines and evaluated tumor antigen-specific CD8+ T cell responses to these melanomas in the context of tumor-free versus tumor-involved lymph nodes. We demonstrate that CD8+ T cells recognizing antigen from established melanomas fail to acquire effector function, regardless of whether the tumor is stable or progressive. This CD8+ T cell dysfunction arises in the context of both tumor-involved and tumor-free lymph nodes draining established melanomas.
Conclusions
Lymph node invasion by melanoma cells is not required for the induction of incomplete CD8+ T cell differentiation. These data and their implications for strategies to enhance CD8+ T cell responses against poorly immunogenic melanomas are discussed herein.
{"title":"Lymph Node Invasion by Melanoma Cells Is Not Required for the Induction of Incomplete Differentiation by Tumor-Specific CD8+ T Cells","authors":"Kristian M. Hargadon, Travis B. Goodloe III, Stephen L. Woodall II","doi":"10.1002/cnr2.70145","DOIUrl":"https://doi.org/10.1002/cnr2.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lymph node invasion by cancer cells is a poor prognostic factor and is often associated with anti-tumor CD8+ T cell dysfunction. In this study, we investigated the role of lymph node invasion by melanoma cells in the induction of incomplete differentiation by tumor antigen-specific CD8+ T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to determine whether lymph node invasion by melanoma cells is required for this specific form of anti-tumor CD8+ T cell dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We assessed lymph node invasion by the B16-F1 and D5.1G4 murine melanoma cell lines and evaluated tumor antigen-specific CD8+ T cell responses to these melanomas in the context of tumor-free versus tumor-involved lymph nodes. We demonstrate that CD8+ T cells recognizing antigen from established melanomas fail to acquire effector function, regardless of whether the tumor is stable or progressive. This CD8+ T cell dysfunction arises in the context of both tumor-involved and tumor-free lymph nodes draining established melanomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Lymph node invasion by melanoma cells is not required for the induction of incomplete CD8+ T cell differentiation. These data and their implications for strategies to enhance CD8+ T cell responses against poorly immunogenic melanomas are discussed herein.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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