Cancers最新文献

{"title":"Risk Factors and Dental Caries Incidence in Childhood Cancer Survivors.","authors":"Anna Jodłowska, Danuta Ilczuk-Rypuła","doi":"10.3390/cancers17061003","DOIUrl":"10.3390/cancers17061003","url":null,"abstract":"<p><strong>Background/objectives: </strong>Dental caries is believed to be one of the most frequent dental long-term adverse effects of anticancer therapy. It may occur due to numerous chemotherapy-dependent oral symptoms or due to the possible neglection of oral care because of parental involvement in the monitoring of other long-term effects of the therapy. This study aimed to determine the incidence of dental caries and the impact of other risk factors in cancer survivors and age-matched controls.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on 40 cancer survivors and 80 peers divided into three age groups. Indices such as dmft/s, DMFT/S, ft/s, FT/S, Plaque Index (PI), and Gingival Index (GI) were calculated to compare the study participants. The sum of dmft and DMFT was used to assess the possible impact of socioeconomic, oral hygiene, and dietary factors.</p><p><strong>Results: </strong>Caries frequency was found to be lower in cancer survivors (92.50%) than in controls (97.50%). No statistically significant differences were found between the study groups within all the caries indices examined. Strong positive correlations with PI and cariogenic diet in the youngest survivors and with PI in middle-aged survivors were observed. Strong negative correlations in middle-aged children were noticed in terms of father's education in survivors and mother's education in controls.</p><p><strong>Conclusions: </strong>The study findings suggest that there is no relationship between chemotherapy and dental caries in long-term cancer survivors. Careful dental care still remains a major contributor to maintaining oral health.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.","authors":"Piotr Strzałka, Kinga Krawiec, Aneta Wiśnik, Dariusz Jarych, Magdalena Czemerska, Izabela Zawlik, Agnieszka Pluta, Agnieszka Wierzbowska","doi":"10.3390/cancers17061009","DOIUrl":"10.3390/cancers17061009","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) corresponds to a heterogeneous group of clonal hematopoietic diseases, which are characterized by uncontrolled proliferation of malignant transformed myeloid precursors and their inability to differentiate into mature blood cells. The prognosis of AML depends on many variables, including the genetic features of the disease. Treatment outcomes, despite the introduction of new targeted therapies, are still unsatisfactory. Recently, there have been an increasing number of reports on enzymatic proteins of the sirtuin family and their potential importance in cancer in general. Sirtuins are a group of 7 (SIRT1-7) NAD+-dependent histone deacetylases with pleiotropic effects on metabolism, aging processes, and cell survival. They are not only responsible for post-translational modification of histones but also play various biochemical functions and interact with other proteins regulating cell survival, such as p53. Thus, their role in key mechanisms of tumorigenesis makes them a worthwhile topic in AML. Different sirtuins have been shown to act oppositely depending on the biological context, the mechanism of which requires further exploration. This review provides a comprehensive description of the significance and role of sirtuins in AML in light of the current state of knowledge. It focuses in particular on molecular mechanisms regulated by sirtuins and signaling pathways involved in leukemogenesis, as well as clinical aspects and potential therapeutic targets in AML.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Diagnostic Interval Leads to High Lymphoma Related Mortality in a Prospective Cohort of People with HIV Undergoing Fine Needle Aspiration.","authors":"Samantha L Vogt, Khuthadzo Hlongwane, Arshia Arora, Kennedy Otwombe, Deshan Chetty, Rebecca H Berhanu, Ziyaad Waja, Wendy Stevens, Tanvier Omar, Neil A Martinson, Richard F Ambinder, Rena R Xian","doi":"10.3390/cancers17061005","DOIUrl":"10.3390/cancers17061005","url":null,"abstract":"<p><strong>Background: </strong>HIV is associated with an increased risk of aggressive lymphomas. Lymphadenopathy is common at the time of presentation; therefore, we set out to understand the time to lymphoma diagnosis in people with HIV (PWH) undergoing fine needle aspiration (FNA).</p><p><strong>Methods: </strong>A prospective, observational cohort of PWH, age ≥ 18 years, undergoing FNA in Soweto, South Africa was established between September 2021 and December 2022. Participants were followed up for up to 8 months and provided consent for a medical record review.</p><p><strong>Results: </strong>One hundred and forty-six participants were enrolled, including 76 females (52%) with a median age of 40 years and a median CD4 count of 216 cells/μL. TB was the most common diagnosis (<i>n</i> = 62; 42%), followed by lymphoma (<i>n</i> = 21; 14%), of whom 10 (48%) died either prior to diagnosis or initiating chemotherapy. An additional 2 participants (10%) were still awaiting a biopsy confirmation at 8 months. One participant's FNA was suggestive of both lymphoma and TB. The median healthcare provider interval, the time from presentation to diagnosis, was 85 days.</p><p><strong>Conclusions: </strong>While TB was the most common diagnosis among PWH undergoing FNA, lymphoma was the leading cause of death. As most deaths occurred prior to chemotherapy, interventions to expedite a lymphoma diagnosis in this high-risk population are needed.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-γδ T Cells Targeting Claudin18.2 Show Superior Cytotoxicity Against Solid Tumor Compared to Traditional CAR-αβ T Cells.","authors":"Yueqi Zhao, Yinghui Li, Shuaiqi Wang, Jingyi Han, Mingyang Lu, Yupeng Xu, Wenhua Qiao, Menghua Cai, Yi Xu, Yu Hu, Jianmin Zhang, Hui Chen, Wei He","doi":"10.3390/cancers17060998","DOIUrl":"10.3390/cancers17060998","url":null,"abstract":"<p><strong>Background: </strong>Claudin18.2 (CLDN18.2) is highly expressed during the development of various malignant tumors, especially gastric cancer, and CAR-T cells targeting CLDN18.2 have therapeutic potential. However, their dependence on the major histocompatibility complex (MHC) for antigen recognition limits their application. Human Gamma Delta (γδ) T cells, with strong MHC-independent cytotoxicity to most solid tumors both in vivo and in vitro, are emerging as ideal cells for the generation of robust universal CLDN18.2 CAR-T cells to treat solid tumors. Our aim was to construct a universal CAR-γδ T cell targeting CLDN18.2.</p><p><strong>Methods: </strong>We constructed novel CAR-CLDN18.2-γδ T cells by lentiviral infection and compared their superior efficacy in the treatment of CLDN18.2-positive solid tumors in vivo and in vitro.</p><p><strong>Results: </strong>CD3ζ expression was verified in HEK293T cells after lentiviral transfection of CLDN18.2 CAR, and the lentivirus was packaged and concentrated to a titer of 4.90 × 10⁸ TU/mL. Primary γδ T cells and αβ T cells were infected with efficiencies of approximately 31.76 ± 4.122% and 44.13 ± 4.436%, respectively. CAR-CLDN18.2-γδ T cells exhibited specific cytotoxicity against CLDN18.2-positive gastric cancer cells and secreted relatively high levels of Granzyme-B, Perforin-1, and IFN-γ. CAR-γδ T cells also showed superior cytotoxicity to target cells compared to classical CAR-αβ T cells in vitro. Finally, the antitumor activity of γδ T-CAR-CLDN18.2 cells was evaluated in tumor-bearing NSG mice, and CAR-CLDN18.2-γδ T cells significantly inhibited tumor growth and prolonged the survival of the mice.</p><p><strong>Conclusions: </strong>Our results demonstrate that universal CAR-CLDN18.2-γδ T cell is promising for the treatment of CLDN18.2-positive solid tumor and provide insights for the development of more universal CAR-γδ T-cell strategies for tumor immunotherapy.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Induced Pluripotent Stem Cell-Derived Astrocytes on Cisplatin Sensitivity in Pediatric Brain Cancer Cells.","authors":"Sonia Kiran, Yu Xue, Drishty B Sarker, Qing-Xiang Amy Sang","doi":"10.3390/cancers17060997","DOIUrl":"10.3390/cancers17060997","url":null,"abstract":"<p><p><b>Background:</b> ATRTs and DIPGs are deadly pediatric brain tumors with poor prognosis. These tumors can develop resistance to chemotherapies, which may be significantly influenced by their microenvironment. Since astrocytes are the most abundant glial cell type in the brain microenvironment and may support tumor growth and chemoresistance, this study investigated the effects of induced pluripotent stem cell-derived astrocytes (iPSC-astrocytes) on cisplatin sensitivity in CHLA-05-ATRT and SF8628 (DIPG) cells. iPSCs provide an unlimited and standardized source of nascent astrocytes, which enables modeling the interaction between childhood brain tumor cells and iPSC-astrocytes within a controlled coculture system. <b>Methods:</b> To study the effects on tumor growth, the iPSC-astrocytes were cocultured with tumor cells. Additionally, the tumor cells were exposed to various concentrations of cisplatin to evaluate their chemosensitivity in the presence of astrocytes. <b>Results:</b> The paracrine interaction of iPSC-astrocytes with tumor cells upregulated astrocyte activation markers GFAP and STAT3 and promoted tumor cell proliferation. Moreover, the cisplatin treatment significantly decreased the viability of CHLA-05-ATRT and SF8628 cells. However, tumor cells exhibited reduced sensitivity to cisplatin in the coculture with iPSC-astrocytes. During cisplatin treatment, DIPG cells in particular showed upregulation of resistance markers, ERK1, STAT3, and MTDH, which are associated with enhanced proliferation and invasion. They also had increased expression of APEX1, which is involved in the base excision repair pathway following cisplatin-induced DNA damage. <b>Conclusion:</b> These findings underscore the significance of the tumor microenvironment in modulating tumor cell survival and chemosensitivity.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Genomic Instability-Associated LncRNAs as Potential Therapeutic Targets in Lung Adenocarcinoma.","authors":"Vanessa G P Souza, Katya H Benard, Greg L Stewart, Katey S S Enfield, Wan L Lam","doi":"10.3390/cancers17060996","DOIUrl":"10.3390/cancers17060996","url":null,"abstract":"<p><strong>Background/objectives: </strong>Non-small cell lung cancer (NSCLC) is the most common type of cancer, with lung adenocarcinoma (LUAD) as the predominant subtype. Despite advancements in targeted therapies, many NSCLC patients still experience poor outcomes due to treatment resistance and disease progression. Genomic instability (GI), a hallmark of cancer, defined as the increased tendency of DNA mutations and alterations, is closely linked to cancer initiation, progression, and resistance to therapy. Emerging evidence suggests that long non-coding RNAs (lncRNAs)-molecules longer than 200 nucleotides that do not encode proteins but regulate gene expression-play critical roles in cancer biology and are associated with GI. However, the relationship between GI and lncRNA expression in LUAD remains poorly understood.</p><p><strong>Methods: </strong>In this study, we analyzed the transcript profiles of lncRNAs and mRNAs from LUAD samples in The Cancer Genome Atlas (TCGA) database and classified them based on their Homologous Recombination Deficiency (HRD) score. The HRD score is an unweighted sum of three independent DNA-based measures of genomic instability: loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions. We then performed a differential gene expression analysis to identify lncRNAs and mRNAs that were either upregulated or downregulated in samples with high HRD scores compared to those with low HRD scores. Following this, we conducted a correlation analysis to assess the significance of the association between HRD scores and the expression of both lncRNAs and mRNAs.</p><p><strong>Results: </strong>We identified 30 differentially expressed lncRNAs and 200 mRNAs associated with genomic instability. Using an RNA interactome database from sequencing experiments, we found evidence of interactions between GI-associated lncRNAs (GI-lncRNAs) and GI-associated mRNAs (GI-mRNAs). Further investigation showed that some GI-lncRNAs play regulatory and functional roles in LUAD and other diseases. We also found that GI-lncRNAs have potential as prognostic biomarkers, particularly when integrated with HRD stratification. The expression of specific GI-lncRNAs was associated with primary therapy response and immune infiltration in LUAD. Additionally, we identified existing drugs that could modulate GI-lncRNAs, offering potential therapeutic strategies to address GI in LUAD.</p><p><strong>Conclusions: </strong>Our findings suggest that GI-associated lncRNAs could serve as valuable biomarkers for LUAD prognosis and therapeutic response. Furthermore, modulating these lncRNAs presents potential treatment avenues to address genomic instability in LUAD.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Axl Regulation of NK Cell Activity Creates an Immunosuppressive Tumor Immune Microenvironment in Head and Neck Cancer.","authors":"Kourtney L Kostecki, Regan L Harmon, Mari Iida, Madelyn A Harris, Bridget E Crossman, Justine Yang Bruce, Ravi Salgia, Deric L Wheeler","doi":"10.3390/cancers17060994","DOIUrl":"10.3390/cancers17060994","url":null,"abstract":"<p><p><i>Background</i>: Head and neck cancer (HNC) evades immune responses by manipulating the tumor immune microenvironment (TIME). Tumor-bound Axl has been implicated in promoting an immunosuppressive TIME in HNC, though its precise role remains unclear. Understanding Axl's contribution to immune evasion in HNC could lead to the identification of new therapeutic targets; therapies directed at these targets could be combined with and thereby enhance immunotherapies. <i>Results:</i> Using Axl knockout (Axl KO) cell lines derived from the immunologically \"cold\" MOC2 mouse model, we found that Axl loss delayed tumor growth in immunocompetent mice. This was accompanied by reduced immunosuppressive cells, including MDSCs, T_regs, B cells, and neutrophils, and increased infiltration of cytotoxic CD8 T cells and NK cells. To identify the immune population(s) responsible for these changes, Axl KO tumors were implanted in immune-deficient mice. Axl KO tumor growth in athymic nude mice (which lack T cells) was unchanged, whereas tumor growth in NCG mice (which lack NK cells) was rescued, suggesting that NK cells mediate the Axl KO tumor growth delay. Further, Axl loss enhanced NK cell cytotoxicity in vitro and in vivo, and NK cell depletion reversed delayed Axl KO tumor growth. Mechanistically, Axl KO tumors showed decreased expression of CD73 and CCL2, which inhibit NK cells, and increased expression of CCL5 and CXCL10, which promote NK cell recruitment and activation. <i>Conclusions:</i> These novel findings suggest that tumor-bound Axl fosters an immunosuppressive TIME by inhibiting NK cell recruitment and function, thereby promoting tumor growth. Targeting Axl may enhance NK cell-mediated tumor killing and improve immunotherapy efficacy in HNC.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Diagnostic and Prognostic Role of Inflammatory Markers, Including the New Cumulative Inflammatory Index (IIC) and Mean Corpuscular Volume/Lymphocyte (MCVL), in Colorectal Adenocarcinoma.","authors":"Robert-Emmanuel Șerban, Dragoș-Marian Popescu, Mihail-Virgil Boldeanu, Dan Nicolae Florescu, Mircea-Sebastian Șerbănescu, Vasile Șandru, Afrodita Panaitescu-Damian, Dragoș Forțofoiu, Rebecca-Cristiana Șerban, Florin-Liviu Gherghina, Cristin-Constantin Vere","doi":"10.3390/cancers17060990","DOIUrl":"10.3390/cancers17060990","url":null,"abstract":"<p><p><b>Background</b>: Colorectal cancer affects a large number of patients worldwide, with numerous factors being involved in its etiopathogenesis and chronic inflammation playing an essential role in tumor development. In this study, we analyzed and compared several markers of inflammation that are relatively easy to obtain for a rapid and accurate diagnosis and prognosis. <b>Methods</b>: This study included 219 patients diagnosed with colorectal cancer, analyzing the inflammation scores derived from their blood cells and inflammatory circulating proteins. These inflammatory markers are neutrophil-to-lymphocyte ratio-NLR; platelet-to-lymphocyte ratio-PLR; lymphocyte-to-monocyte ratio-LMR; systemic immune inflammation index-SII; systemic inflammatory response index-SIRI; aggregate index of systemic inflammation-AISI; derived neutrophil-to-lymphocyte ratio-dNLR; C-reactive protein-to-albumin ratio-CAR; and fibrinogen-to-albumin ratio-FAR. In the analysis of patients with colorectal cancer, we have also introduced two new recently developed inflammatory markers: the cumulative inflammatory index (IIC) and the ratio between the mean corpuscular volume and lymphocytes (MCVL). This study aimed to correlate the inflammatory markers' levels with the colorectal cancer diagnostic stage, the tumor and clinical characteristics of the colorectal cancer patients, and 36 months' survival time and to evaluate the diagnostic and prognostic capacity and accuracy of these inflammatory markers in this type of cancer. <b>Results</b>: We showed that the levels of the analyzed inflammation markers correlate with the TNM stage, the tumor pathological differentiation grade, the age and gender of the patients, and overall survival, with their increased levels being associated with a lower survival rate. <b>Conclusions</b>: The analyzed markers, which are easy to perform right from the patient's admission, can be helpful both in diagnosis and, mostly, in prognosis, sustaining the role of inflammation in cancer. By comparing them, we showed which one can be useful for increased sensitivity and specificity in the diagnosis and prognosis of colorectal cancer patients.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases?","authors":"Sarah E Glynn, Claire M Lanier, Ariel R Choi, Ralph D'Agostino, Michael Farris, Mohammed Abdulhaleem, Yuezhu Wang, Margaret Smith, Jimmy Ruiz, Thomas Lycan, William Jeffrey Petty, Christina K Cramer, Stephen B Tatter, Adrian W Laxton, Jaclyn J White, Jing Su, Christopher T Whitlow, David R Soto-Pantoja, Fei Xing, Yuming Jiang, Michael Chan, Corbin A Helis","doi":"10.3390/cancers17060991","DOIUrl":"10.3390/cancers17060991","url":null,"abstract":"<p><p><b>Background/Objectives</b>: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. <b>Methods</b>: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample <i>t</i>-testing was used to identify mutations statistically associated with iBMV (<i>p</i> < 0.1). A value of +1 was assigned to each mutation with a positive association (\"deleterious genes\"), and a value of -1 to each with an inverse association (\"protective genes\"). The sum of these values was calculated to define iBMV risk scores of -1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. <b>Results</b>: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. \"Deleterious genes\" included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; \"protective genes\" included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and -1, predicted an 88%, 61% and 65% likelihood of developing a BM (<i>p</i> < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. -1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and -1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (<i>p</i> < 0.02). <b>Conclusions</b>: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proliferation-Diffusion Modeling in Glioblastoma: Impact of Supramaximal Resection on Survival.","authors":"Maria Pia Tropeano, Zefferino Rossini, Ettore Bresciani, Andrea Franzini, Beatrice C Bono, Pierina Navarria, Elena Clerici, Matteo Simonelli, Marta Scorsetti, Marco Riva, Letterio Salvatore Politi, Federico Pessina","doi":"10.3390/cancers17060995","DOIUrl":"10.3390/cancers17060995","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the role of tumor invasiveness profile in a homogeneous cohort of patients with newly diagnosed GBM (2021 WHO) that underwent SUPR by the RANO criteria, and to analyze its impact on survival outcomes.</p><p><strong>Methods: </strong>Patients with newly diagnosed, histologically confirmed glial tumors featuring contrast-enhancing lesions, who underwent surgery at our institution between January 2007 and January 2024, were retrospectively reviewed. Preoperative total tumor volume (T-TV), contrast-enhancing (CE), and infiltrative FLAIR tumor volume (FLAIR-TV) were calculated in cubic centimeters (cc) via manual segmentation. A neuronavigation system was utilized for surgery and lesions were molecularly evaluated following the 2021 WHO CNS tumor classification. Therefore, all patients were classified into extent of resection categories by the 2022 RANO-Resect classification. The tumor invasiveness profile was assessed using the proliferation/diffusion (ρ/D) ratio, calculated following Swanson's method. A statistical analysis was finally performed.</p><p><strong>Results: </strong>Between 2007 and 2024, 410 adult patients with newly diagnosed gliomas were treated at our institution. Methylation of the MGMT promoter was statistically significant (HR = 0.43, 95% CI: 0.20-0.94, <i>p</i> = 0.035), indicating that methylation has a protective effect on survival. In multivariate analysis, only MGMT status was confirmed to be an independent predictor of overall survival (OS). MGMT methylation was significantly associated with improved progression-free survival (PFS) in moderately diffuse tumors (HR = 0.18, 95% CI: 0.03-0.95, <i>p</i> = 0.044).</p><p><strong>Conclusions: </strong>Using the proliferation-diffusion model to classify tumors, we identified moderately diffuse tumors with methylated MGMT status as a subgroup with significant survival benefits from SUPR.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}