Yuting Wang, Nan Zhang, Weilong Shang, Huagang Peng, Zhen Hu, Yi Yang, Li Tan, Li Zhang, Fengtian He, Xiancai Rao
Background
Dexamethasone (Dex), a synthetic glucocorticoid that acts by binding to the glucocorticoid receptor (GR), has been widely applied to treat leukemia and lymphoma; however, the precise mechanism underlying Dex action is still not well elucidated. DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, has been linked to multiple cancer types, particularly mixed lineage leukemia (MLL) gene rearranged leukemia, but its contribution to lymphoma is yet to be delineated. Analysis from the TCGA database displayed that DOT1L was highly expressed in lymphoma and leukemia.
Results
We initially demonstrated that DOT1L served as a new target gene controlled by GR, and the downregulation of DOT1L was critical for the killing of B-lymphoma cells by Dex. Further study revealed that Dex had no impact on the transcriptional activity of the DOT1L promoter, rather it reduced the mRNA level of DOT1L at the posttranscriptional level. In addition, knockdown of DOT1L remarkably inhibited the B-lymphoma cell growth.
Conclusions
Overall, our findings indicated that DOT1L may serve as a potential drug target and a promising biomarker of Dex sensitivity when it comes to treating B lymphoma.
背景地塞米松（Dex）是一种通过与糖皮质激素受体（GR）结合而发挥作用的合成糖皮质激素，已被广泛应用于治疗白血病和淋巴瘤；然而，地塞米松作用的确切机制仍未得到很好的阐明。DOT1L是一种组蛋白H3-赖氨酸79（H3K79）甲基转移酶，它与多种癌症类型有关，尤其是与混合系白血病（MLL）基因重排的白血病有关，但它对淋巴瘤的作用尚未明确。对 TCGA 数据库的分析表明，DOT1L 在淋巴瘤和白血病中高度表达。 结果 我们初步证明 DOT1L 是受 GR 控制的新靶基因，DOT1L 的下调对 Dex 杀死 B 淋巴瘤细胞至关重要。进一步研究发现，Dex对DOT1L启动子的转录活性没有影响，而是在转录后水平降低了DOT1L的mRNA水平。此外，敲除 DOT1L 能显著抑制 B 淋巴瘤细胞的生长。 结论 总的来说，我们的研究结果表明，DOT1L可作为治疗B淋巴瘤的潜在药物靶点和Dex敏感性的生物标志物。
{"title":"Dexamethasone Inhibits the Growth of B-Lymphoma Cells by Downregulating DOT1L","authors":"Yuting Wang, Nan Zhang, Weilong Shang, Huagang Peng, Zhen Hu, Yi Yang, Li Tan, Li Zhang, Fengtian He, Xiancai Rao","doi":"10.1002/cnr2.2150","DOIUrl":"https://doi.org/10.1002/cnr2.2150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dexamethasone (Dex), a synthetic glucocorticoid that acts by binding to the glucocorticoid receptor (GR), has been widely applied to treat leukemia and lymphoma; however, the precise mechanism underlying Dex action is still not well elucidated. DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, has been linked to multiple cancer types, particularly mixed lineage leukemia (MLL) gene rearranged leukemia, but its contribution to lymphoma is yet to be delineated. Analysis from the TCGA database displayed that DOT1L was highly expressed in lymphoma and leukemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We initially demonstrated that DOT1L served as a new target gene controlled by GR, and the downregulation of DOT1L was critical for the killing of B-lymphoma cells by Dex. Further study revealed that Dex had no impact on the transcriptional activity of the DOT1L promoter, rather it reduced the mRNA level of DOT1L at the posttranscriptional level. In addition, knockdown of DOT1L remarkably inhibited the B-lymphoma cell growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, our findings indicated that DOT1L may serve as a potential drug target and a promising biomarker of Dex sensitivity when it comes to treating B lymphoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.2150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276582","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}
Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable gene alterations in non-small cell lung cancer (NSCLC). In Japan, approximately 40% of patients who undergo surgical resection for non-squamous NSCLC have EGFR mutations. However, no long-term studies have been conducted including a large number of EGFR-positive NSCLC patients with postoperative recurrence (PR).
Methods
We conducted a retrospective observational study of the data of EGFR-positive NSCLC patients with PR who had undergone surgery at the Shizuoka Cancer Center between October 2002 and November 2017. We evaluated post-recurrence overall survival (PRS) and postoperative overall survival (POS) using the Kaplan–Meier method and identify any associations between the clinical variables at recurrence and PRS using univariate and multivariate analysis.
Results
We enrolled 162 patients. The median observation time for PRS was 4.95 years (range, 0.82–13.25) and POS was 5.81 years (range, 2.84–16.71). The median PRS was 5.17 years (95% confidence interval [CI], 3.90–5.61) and POS was 7.07 years (95% CI, 5.88–8.01). Univariate analysis identified male sex (median PRS: 3.32 vs. 5.39 years; p < 0.05), bone metastasis (median PRS: 2.43 vs. 5.33 years; p < 0.05), and central nervous system (CNS) metastasis (median PRS: 3.05 vs. 5.39 years; p < 0.05) and multivariate analysis identified bone metastasis (hazard ratio [HR], 2.01; 95% CI, 1.23–3.28; p < 0.05) and CNS metastasis (HR, 1.84; 95% CI, 1.14–2.98; p < 0.05) as poor prognostic factors. The pattern of recurrence (oligo vs. non-oligo recurrence) was not a prognostic factor. Logistic regression analysis revealed the association between sex and the presence bone/CNS metastasis at recurrence.
Conclusion
Our data may help visualize future prospects and determine the timing of osimertinib initiation. New treatment strategies need to be developed for patients with bone/CNS metastasis at the first recurrence.
{"title":"Prognostic Impact of Postoperative Recurrence in Patients With Epidermal Growth Factor Receptor–Positive Non-Small Cell Lung Cancer","authors":"Meiko Morita, Akira Ono, Motoki Sekikawa, Kosei Doshita, Keita Miura, Hiroaki Kodama, Michitoshi Yabe, Noboru Morikawa, Yuko Iida, Nobuaki Mamesaya, Haruki Kobayashi, Ryo Ko, Kazushige Wakuda, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Mitsuhiro Isaka, Yasuhisa Ohde, Toshiaki Takahashi","doi":"10.1002/cnr2.70004","DOIUrl":"10.1002/cnr2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mutations in the epidermal growth factor receptor (<i>EGFR</i>) gene are the most common targetable gene alterations in non-small cell lung cancer (NSCLC). In Japan, approximately 40% of patients who undergo surgical resection for non-squamous NSCLC have <i>EGFR</i> mutations. However, no long-term studies have been conducted including a large number of <i>EGFR</i>-positive NSCLC patients with postoperative recurrence (PR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective observational study of the data of <i>EGFR</i>-positive NSCLC patients with PR who had undergone surgery at the Shizuoka Cancer Center between October 2002 and November 2017. We evaluated post-recurrence overall survival (PRS) and postoperative overall survival (POS) using the Kaplan–Meier method and identify any associations between the clinical variables at recurrence and PRS using univariate and multivariate analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We enrolled 162 patients. The median observation time for PRS was 4.95 years (range, 0.82–13.25) and POS was 5.81 years (range, 2.84–16.71). The median PRS was 5.17 years (95% confidence interval [CI], 3.90–5.61) and POS was 7.07 years (95% CI, 5.88–8.01). Univariate analysis identified male sex (median PRS: 3.32 vs. 5.39 years; <i>p</i> < 0.05), bone metastasis (median PRS: 2.43 vs. 5.33 years; <i>p</i> < 0.05), and central nervous system (CNS) metastasis (median PRS: 3.05 vs. 5.39 years; <i>p</i> < 0.05) and multivariate analysis identified bone metastasis (hazard ratio [HR], 2.01; 95% CI, 1.23–3.28; <i>p</i> < 0.05) and CNS metastasis (HR, 1.84; 95% CI, 1.14–2.98; <i>p</i> < 0.05) as poor prognostic factors. The pattern of recurrence (oligo vs. non-oligo recurrence) was not a prognostic factor. Logistic regression analysis revealed the association between sex and the presence bone/CNS metastasis at recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data may help visualize future prospects and determine the timing of osimertinib initiation. New treatment strategies need to be developed for patients with bone/CNS metastasis at the first recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153173","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}
Trine Stub, Marleen Mathisen, Lene Thorsen, Cecilie E. Kiserud, Hanne C. Lie
Background
Cancer-related fatigue is a common and distressing late effect of cancer that can persist for decades after treatment completion. Although negatively affecting survivors' quality of life, few, if any, efficacious interventions for persistent, or chronic, fatigue exist.
Aims
To inform future interventions, we explored how long-term, young adult cancer survivors (YACSs) with chronic fatigue live with, and manage their fatigue over time, including their experiences with nonpharmacological interventions (NPIs) for chronic fatigue.
Methods and Results
We conducted a qualitative focus group study with 15 YACSs (13 women) with chronic fatigue, on average 7.3 years post-diagnosis. The YACS were identified and recruited through a nationwide health survey of cancer survivors (the NOR-CAYACS study). Systematic content analysis was used to identify recurrent themes. Analysis revealed five themes: (1) manifestation of fatigue, detailing chronic fatigue experiences; (2) impact on daily life, highlighting the necessity to balance rest and activity, affecting relationships; (3) NPIs, where walks in nature were notably beneficial; (4) barriers to fatigue management, including energy deficits, treatment-related bodily changes, and self-care prioritization challenges; (5) facilitators to fatigue management, emphasizing the need for regular breaks, self-care practices, and the importance of fatigue management education.
Conclusion
This study offers novel insights into the lived experiences of YACSs with chronic fatigue, a subject scarcely examined in prior research. Our findings highlight the significant impact of chronic fatigue and the individualized strategies YACSs use to cope. The research emphasizes the need for personalized interventions to support chronic fatigue management, marking a critical step forward in addressing this often-overlooked issue in survivorship care. Future research should focus on tailored approaches to improve YACSs' quality of life.
{"title":"Experiences Using Nonpharmacological Interventions for Chronic Fatigue: A Focus Group Study of Long-Term Survivors of Young Adult Cancers With Fatigue","authors":"Trine Stub, Marleen Mathisen, Lene Thorsen, Cecilie E. Kiserud, Hanne C. Lie","doi":"10.1002/cnr2.2139","DOIUrl":"10.1002/cnr2.2139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer-related fatigue is a common and distressing late effect of cancer that can persist for decades after treatment completion. Although negatively affecting survivors' quality of life, few, if any, efficacious interventions for persistent, or chronic, fatigue exist.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To inform future interventions, we explored how long-term, young adult cancer survivors (YACSs) with chronic fatigue live with, and manage their fatigue over time, including their experiences with nonpharmacological interventions (NPIs) for chronic fatigue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We conducted a qualitative focus group study with 15 YACSs (13 women) with chronic fatigue, on average 7.3 years post-diagnosis. The YACS were identified and recruited through a nationwide health survey of cancer survivors (the NOR-CAYACS study). Systematic content analysis was used to identify recurrent themes. Analysis revealed five themes: (1) manifestation of fatigue, detailing chronic fatigue experiences; (2) impact on daily life, highlighting the necessity to balance rest and activity, affecting relationships; (3) NPIs, where walks in nature were notably beneficial; (4) barriers to fatigue management, including energy deficits, treatment-related bodily changes, and self-care prioritization challenges; (5) facilitators to fatigue management, emphasizing the need for regular breaks, self-care practices, and the importance of fatigue management education.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study offers novel insights into the lived experiences of YACSs with chronic fatigue, a subject scarcely examined in prior research. Our findings highlight the significant impact of chronic fatigue and the individualized strategies YACSs use to cope. The research emphasizes the need for personalized interventions to support chronic fatigue management, marking a critical step forward in addressing this often-overlooked issue in survivorship care. Future research should focus on tailored approaches to improve YACSs' quality of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131914","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}
Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC.
Purpose
This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets.
Methods
The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan–Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients.
Results
A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients.
Conclusions
Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.
{"title":"Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC","authors":"Shaowen Hu, Xiaoli Zhang, Huiru Xin, Mingjie Guo, Yafei Xiao, Zhongwei Chang, Qingyang Luo, Yang Li, Chaoyang Zhu","doi":"10.1002/cnr2.70010","DOIUrl":"10.1002/cnr2.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan–Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131916","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}
Chelsea S. Rapoport, Diane Masser-Frye, Sapna Mehta, Alyssa K. Choi, Sydney Olfus, Megan Korhummel, Veronica Hoyo, David Dimmock, Vanessa L. Malcarne, Dennis J. Kuo
Background
Cancer predisposition syndromes (CPS) impact about 10% of patients with pediatric cancer. Genetic testing (CPS-GT) has multiple benefits, but few studies have described parent and child knowledge and attitudes regarding CPS-GT decision-making. This study examined parent and patient CPS-GT decision-making knowledge and attitudes.
Procedure
English- or Spanish-speaking parents of children with pediatric cancer and patients with pediatric cancer ages 15–18 within 12 months of diagnosis or relapse were eligible to participate. Seventy-five parents and 19 parent-patient dyads (N = 94 parents, 77.7% female, 43.6% Latino/a/Hispanic; 19 patients, 31.6% female) completed surveys measuring CPS-GT-related beliefs. Independent samples t-tests compared parent responses across sociodemographic characteristics and parent-patient responses within dyads.
Results
Spanish-speaking parents were significantly more likely than English-speaking parents to believe that CPS-GT not being helpful (p < .001) and possibly causing personal distress (p = .002) were important considerations for deciding whether to obtain CPS-GT. Parents with less than four-year university education, income less than $75,000, or Medicaid (vs. private insurance) were significantly more likely to endorse that CPS-GT not being helpful was an important consideration for deciding whether to obtain CPS-GT (p < .001). Parents felt more strongly than patients that they understood what CPS-GT was (p = .01) and that parents should decide whether patients under 18 should receive CPS-GT (p = .002).
Conclusions
Spanish-speaking parents and parents with lower socioeconomic statuses were more strongly influenced by the potential disadvantages of CPS-GT in CPS-GT decision-making. Parents felt more strongly than patients that parents should make CPS-GT decisions. Future studies should investigate mechanisms behind these differences and how to best support CPS-GT knowledge and decision-making.
{"title":"Parent and patient knowledge and attitudes about cancer predisposition syndrome genetic testing in pediatric oncology: Understanding sociodemographic and parent–child differences","authors":"Chelsea S. Rapoport, Diane Masser-Frye, Sapna Mehta, Alyssa K. Choi, Sydney Olfus, Megan Korhummel, Veronica Hoyo, David Dimmock, Vanessa L. Malcarne, Dennis J. Kuo","doi":"10.1002/cnr2.2119","DOIUrl":"10.1002/cnr2.2119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer predisposition syndromes (CPS) impact about 10% of patients with pediatric cancer. Genetic testing (CPS-GT) has multiple benefits, but few studies have described parent and child knowledge and attitudes regarding CPS-GT decision-making. This study examined parent and patient CPS-GT decision-making knowledge and attitudes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Procedure</h3>\u0000 \u0000 <p>English- or Spanish-speaking parents of children with pediatric cancer and patients with pediatric cancer ages 15–18 within 12 months of diagnosis or relapse were eligible to participate. Seventy-five parents and 19 parent-patient dyads (<i>N</i> = 94 parents, 77.7% female, 43.6% Latino/a/Hispanic; 19 patients, 31.6% female) completed surveys measuring CPS-GT-related beliefs. Independent samples <i>t</i>-tests compared parent responses across sociodemographic characteristics and parent-patient responses within dyads.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Spanish-speaking parents were significantly more likely than English-speaking parents to believe that CPS-GT not being helpful (<i>p</i> < .001) and possibly causing personal distress (<i>p</i> = .002) were important considerations for deciding whether to obtain CPS-GT. Parents with less than four-year university education, income less than $75,000, or Medicaid (vs. private insurance) were significantly more likely to endorse that CPS-GT not being helpful was an important consideration for deciding whether to obtain CPS-GT (<i>p</i> < .001). Parents felt more strongly than patients that they understood what CPS-GT was (<i>p</i> = .01) and that parents should decide whether patients under 18 should receive CPS-GT (<i>p</i> = .002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Spanish-speaking parents and parents with lower socioeconomic statuses were more strongly influenced by the potential disadvantages of CPS-GT in CPS-GT decision-making. Parents felt more strongly than patients that parents should make CPS-GT decisions. Future studies should investigate mechanisms behind these differences and how to best support CPS-GT knowledge and decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131918","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 bone is among the most frequently chosen sites for the metastatic spread of breast cancer. The prediction of biomarkers for BM (Bone Metastasis) and PDB (Paget's disease of bone) initiated from breast cancer could be critically important in categorizing individuals with a higher risk and providing targeted treatment for PDB and BM.
Aims
This research aims to investigate the common key candidate biomarkers that contribute to BM-BCa (Bone metastasis of breast cancer) and PDB by employing network decomposition and functional enrichment studies.
Methods and Results
This research analyzed high-throughput transcriptome sequencing (RNA-Seq). For this work, the dataset (GSE121677) was downloaded from GEO (Gene Expression Omnibus), and DEGs were identified using Galaxy and R script 4.3. Using STRING (Search Tool for the Retrieval of Interacting Genes), high-throughput research created a protein-protein interaction network (PPIN). The BM-PDB-interactome was created using Cytoscape 3.9.1 and PDB biomarkers, with the top 3% DEGs from BM-BCa. Functional Enrichment Analysis (Funrich 3.1.3) and DAVID 6.8 performed functional and gene set enrichment analysis (GSEA) of putatively essential biomarkers. TCGA (The Cancer Genome Atlas) validated the discovered genes. Based on our research, we identified 1262 DEGs; among these DEGs, 431 genes were upregulated, and 831 genes were downregulated. During the third growth of the interactome, 20 more genes were pinned to the BM-PDB interactome. RAC2, PIAS1, EP300, EIF2S1, and LRP6 are among the additional 25% of genes identified to interact with the BM-PDB interactome. To corroborate the findings of the research presented, additional functional and gene set enrichment analyses have been performed.
Conclusion
Of the five reported genes (RAC2, PIAS1, EP300, EIF2S1, and LRP6), RAC2 was identified to function as the common key potential biomarker in the BM-PDB interactome analysis and validated by TCGA in the study presented.
{"title":"Identification of Biomarkers Associated With Paget's Disease of Bone and Bone Metastasis From Breast Cancer Patients","authors":"Mahima Bhardwaj, Farhana Begum, Duleswar Singh, Srirama Krupanidhi, Virendra Kumar Yadav, Dipak Kumar Sahoo, Ashish Patel, Sachidanand Singh","doi":"10.1002/cnr2.70003","DOIUrl":"10.1002/cnr2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The bone is among the most frequently chosen sites for the metastatic spread of breast cancer. The prediction of biomarkers for BM (Bone Metastasis) and PDB (Paget's disease of bone) initiated from breast cancer could be critically important in categorizing individuals with a higher risk and providing targeted treatment for PDB and BM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This research aims to investigate the common key candidate biomarkers that contribute to BM-BCa (Bone metastasis of breast cancer) and PDB by employing network decomposition and functional enrichment studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>This research analyzed high-throughput transcriptome sequencing (RNA-Seq). For this work, the dataset (GSE121677) was downloaded from GEO (Gene Expression Omnibus), and DEGs were identified using Galaxy and R script 4.3. Using STRING (Search Tool for the Retrieval of Interacting Genes), high-throughput research created a protein-protein interaction network (PPIN). The BM-PDB-interactome was created using Cytoscape 3.9.1 and PDB biomarkers, with the top 3% DEGs from BM-BCa. Functional Enrichment Analysis (Funrich 3.1.3) and DAVID 6.8 performed functional and gene set enrichment analysis (GSEA) of putatively essential biomarkers. TCGA (The Cancer Genome Atlas) validated the discovered genes. Based on our research, we identified 1262 DEGs; among these DEGs, 431 genes were upregulated, and 831 genes were downregulated. During the third growth of the interactome, 20 more genes were pinned to the BM-PDB interactome. RAC2, PIAS1, EP300, EIF2S1, and LRP6 are among the additional 25% of genes identified to interact with the BM-PDB interactome. To corroborate the findings of the research presented, additional functional and gene set enrichment analyses have been performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Of the five reported genes (RAC2, PIAS1, EP300, EIF2S1, and LRP6), RAC2 was identified to function as the common key potential biomarker in the BM-PDB interactome analysis and validated by TCGA in the study presented.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131915","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}
According to the 2020 statistics from the World Health Organization’s International Agency for Research on Cancer (IARC), it is projected that there will be over 1 million new cases of gastric cancer (GC) patients worldwide in 2020, resulting in approximately 770 000 deaths. Gastric cancer ranks fifth in terms of incidence rate and forth in death rate among malignant tumors. Despite advancements in early diagnostic techniques, the incidence of GC has exhibited a marginal decline; nevertheless, the mortality rate remains elevated for advanced inoperable patients with no currently available efficacious treatment options.
Recent Finding
Chinese medicine (CM) has emerged as an efficacious treatment for GC, gradually gaining acceptance and widespread usage in China. It exhibits distinctive advantages in the prevention and treatment of metastasis. CM and natural medicine possess the ability to elicit antitumor effects by augmenting immune cell population, enhancing immune cell activity, and improving the tumor immune microenvironment. CMs and natural remedies encompass a diverse range of types, characterized by multiple targets, pathways, and extensive pharmacological effects. Consequently, they have become a prominent research area among oncologists worldwide. Numerous studies have demonstrated that CM and natural medicine can directly or indirectly enhance innate immune system components (including macrophages, natural killer cells, and myeloid suppressor cells), adaptive immune system elements (such as T lymphocytes and regulatory T cells), relevant cytokines (e.g., IL-2, IL-4, IL-10, TNF-α), and PD-1/PD-L1 axis regulation, thereby bolstering the cytotoxicity of immune cells against tumor cells.
Conclusions
This ultimately leads to an improved tumor immune microenvironment facilitating superior antitumor efficacy. This paper critically examines the role of CM and natural medicine in regulating immunotherapy for GC, aiming to establish a new theoretical framework for the clinical treatment and prevention of gastric cancer within the realm of CM.
背景：根据世界卫生组织国际癌症研究机构（IARC）2020 年的统计数据，预计 2020 年全球胃癌（GC）新病例将超过 100 万例，导致约 77 万人死亡。胃癌的发病率在恶性肿瘤中排名第五，死亡率排名第四。尽管早期诊断技术不断进步，胃癌的发病率已略有下降；然而，无法手术的晚期患者的死亡率仍然很高，而且目前尚无有效的治疗方案：最新研究结果：中药已成为治疗胃癌的一种有效方法，在中国逐渐被接受和广泛使用。它在预防和治疗转移方面具有独特的优势。中药和天然药物能够通过增加免疫细胞数量、提高免疫细胞活性和改善肿瘤免疫微环境来发挥抗肿瘤作用。中药和天然药物种类繁多，具有多靶点、多途径和广泛药理作用的特点。因此，它们已成为全球肿瘤学家的一个重要研究领域。大量研究表明，中药和天然药物可直接或间接增强先天性免疫系统成分（包括巨噬细胞、自然杀伤细胞和骨髓抑制细胞）、适应性免疫系统成分（如 T 淋巴细胞和调节性 T 细胞）、相关细胞因子（如 IL-2、IL-4、IL-10、TNF-α）和 PD-1/PD-L1 轴调控，从而增强免疫细胞对肿瘤细胞的细胞毒性：结论：这最终会导致肿瘤免疫微环境的改善，从而提高抗肿瘤疗效。本文对中药和天然药物在胃癌免疫治疗中的调控作用进行了深入研究，旨在为中药在胃癌临床治疗和预防中建立新的理论框架。
{"title":"Chinese Medicines and Natural Medicine as Immunotherapeutic Agents for Gastric Cancer: Recent Advances","authors":"Zhipeng Zhang, Ziqi Chen, Zujun Que, Zhihong Fang, Huirong Zhu, Jianhui Tian","doi":"10.1002/cnr2.2134","DOIUrl":"10.1002/cnr2.2134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgroud</h3>\u0000 \u0000 <p>According to the 2020 statistics from the World Health Organization’s International Agency for Research on Cancer (IARC), it is projected that there will be over 1 million new cases of gastric cancer (GC) patients worldwide in 2020, resulting in approximately 770 000 deaths. Gastric cancer ranks fifth in terms of incidence rate and forth in death rate among malignant tumors. Despite advancements in early diagnostic techniques, the incidence of GC has exhibited a marginal decline; nevertheless, the mortality rate remains elevated for advanced inoperable patients with no currently available efficacious treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent Finding</h3>\u0000 \u0000 <p>Chinese medicine (CM) has emerged as an efficacious treatment for GC, gradually gaining acceptance and widespread usage in China. It exhibits distinctive advantages in the prevention and treatment of metastasis. CM and natural medicine possess the ability to elicit antitumor effects by augmenting immune cell population, enhancing immune cell activity, and improving the tumor immune microenvironment. CMs and natural remedies encompass a diverse range of types, characterized by multiple targets, pathways, and extensive pharmacological effects. Consequently, they have become a prominent research area among oncologists worldwide. Numerous studies have demonstrated that CM and natural medicine can directly or indirectly enhance innate immune system components (including macrophages, natural killer cells, and myeloid suppressor cells), adaptive immune system elements (such as T lymphocytes and regulatory T cells), relevant cytokines (e.g., IL-2, IL-4, IL-10, TNF-α), and PD-1/PD-L1 axis regulation, thereby bolstering the cytotoxicity of immune cells against tumor cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This ultimately leads to an improved tumor immune microenvironment facilitating superior antitumor efficacy. This paper critically examines the role of CM and natural medicine in regulating immunotherapy for GC, aiming to establish a new theoretical framework for the clinical treatment and prevention of gastric cancer within the realm of CM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131913","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}
Surgical resection is the primary treatment option for patients diagnosed with nonfunctional pancreatic neuroendocrine tumors (NF-Pan-NETs). However, the postoperative prognostic evaluation for NF-Pan-NET patients remains obscure. This study aimed to construct an efficient model to predict the prognosis of NF-Pan-NET patients who have received surgical resection.
Methods
NF-Pan-NET patients after pancreatectomy were retrieved from the SEER database for the period of 2010 to 2019. A total of 2844 patients with NF-Pan-NET from SEER database were included in our study. After careful screening, six clinicopathological variables including age, grade, AJCC T stage, AJCC N stage, AJCC M stage, and chemotherapy were selected to develop nomograms to predict overall survival (OS) and cancer-specific survival (CSS) respectively of the patients.
Results
The novel models demonstrated high accuracy and discrimination in prognosticating resected NF-Pan-NET through various validation methods. Furthermore, the risk subgroups classified by the newly developed risk stratification systems based on the nomograms exhibited significant differences in both OS and CSS, surpassing the efficacy of the AJCC 8th TNM staging system. Novel nomograms and corresponding risk classification systems were developed to predict OS and CSS in patients with NF-Pan-NET after pancreatectomy.
Conclusion
The models demonstrated superior performance compared to traditional staging systems, providing clinicians with more accurate and personalized guidance for postoperative surveillance and treatment.
{"title":"Prognostic Nomograms for Patients With NF-Pan-NET After Pancreatectomy: A Retrospective Analysis Based on SEER Database","authors":"Yizhi Wang, Yang Kong, Qifan Yang, Dongkai Zhou","doi":"10.1002/cnr2.2165","DOIUrl":"10.1002/cnr2.2165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Surgical resection is the primary treatment option for patients diagnosed with nonfunctional pancreatic neuroendocrine tumors (NF-Pan-NETs). However, the postoperative prognostic evaluation for NF-Pan-NET patients remains obscure. This study aimed to construct an efficient model to predict the prognosis of NF-Pan-NET patients who have received surgical resection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>NF-Pan-NET patients after pancreatectomy were retrieved from the SEER database for the period of 2010 to 2019. A total of 2844 patients with NF-Pan-NET from SEER database were included in our study. After careful screening, six clinicopathological variables including age, grade, AJCC T stage, AJCC N stage, AJCC M stage, and chemotherapy were selected to develop nomograms to predict overall survival (OS) and cancer-specific survival (CSS) respectively of the patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The novel models demonstrated high accuracy and discrimination in prognosticating resected NF-Pan-NET through various validation methods. Furthermore, the risk subgroups classified by the newly developed risk stratification systems based on the nomograms exhibited significant differences in both OS and CSS, surpassing the efficacy of the AJCC 8th TNM staging system. Novel nomograms and corresponding risk classification systems were developed to predict OS and CSS in patients with NF-Pan-NET after pancreatectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The models demonstrated superior performance compared to traditional staging systems, providing clinicians with more accurate and personalized guidance for postoperative surveillance and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131934","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}
Ewing’s sarcoma (ES) is the second most common malignant primary bone tumor in children and adolescents. Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme.
Aims
Here, we investigated the role and mechanism of PRDX2 in the development of ES.
Methods and results
PRDX2 expression was knocked down in A673 and RDES cells by specific siRNA interference (si-PRDX2). Knockdown of PRDX2 strongly inhibited the proliferation, growth, migration, invasion, and MMP9 activity and induces apoptosis of A673 and RDES cells. si-PRDX2 significantly inhibited the phosphorylation of Akt and the expression of cyclin D1. The transcription factor that might regulate PRDX2 transcription was predicted with the JASPAR and UCSC databases, and analyzed using dual-luciferase and Chromatin co-immunoprecipitation experiments. SNAI1 could activate the transcription of PRDX2 by binding to predicted promoter binding site.
Conclusion
PRDX2 may be a potential therapeutic target for ES.
{"title":"Knockdown of PRDX2 Inhibits the Proliferation, Growth, Migration, Invasion, and MMP9 Activity of Ewing's Sarcoma Cells Cultured In Vitro","authors":"Ruifeng Xue, Zhengfu Fan, Yunhe An","doi":"10.1002/cnr2.2122","DOIUrl":"10.1002/cnr2.2122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ewing’s sarcoma (ES) is the second most common malignant primary bone tumor in children and adolescents. Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Here, we investigated the role and mechanism of PRDX2 in the development of ES.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>PRDX2 expression was knocked down in A673 and RDES cells by specific siRNA interference (si-PRDX2). Knockdown of PRDX2 strongly inhibited the proliferation, growth, migration, invasion, and MMP9 activity and induces apoptosis of A673 and RDES cells. si-PRDX2 significantly inhibited the phosphorylation of Akt and the expression of cyclin D1. The transcription factor that might regulate PRDX2 transcription was predicted with the JASPAR and UCSC databases, and analyzed using dual-luciferase and Chromatin co-immunoprecipitation experiments. SNAI1 could activate the transcription of PRDX2 by binding to predicted promoter binding site.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PRDX2 may be a potential therapeutic target for ES.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131917","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}
Moayed Ibrahim, Catherine Murphree, Kirtesh Patel, Matthew Mastrodomenico, Nakhle S. Saba, Hana Safah, Janet Schmid, Francisco Socola
Background
It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes.
Aims
To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls.
Methods
We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes.
Results
We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t-value 2.05, p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t-value 2.12, p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t-value 1.02, p-value 0.162).
Conclusion
These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.
{"title":"Programmed death-ligand 1 expression in patients with primary or secondary myelofibrosis","authors":"Moayed Ibrahim, Catherine Murphree, Kirtesh Patel, Matthew Mastrodomenico, Nakhle S. Saba, Hana Safah, Janet Schmid, Francisco Socola","doi":"10.1002/cnr2.2054","DOIUrl":"10.1002/cnr2.2054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (<i>t</i>-value 2.05, <i>p</i>-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (<i>t</i>-value 2.12, <i>p</i>-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (<i>t</i>-value 1.02, <i>p</i>-value 0.162).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 9","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131935","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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