Cancer pathogenesis and therapy最新文献

{"title":"Loss of phosphatase and tensin homolog (PTEN) increases Lysyl oxidase-like 2 (LOXL2) expression enhancing the growth of fallopian tube epithelial cells as three-dimensional spheroids","authors":"Angela Russo ,&nbsp;Junlone Moy ,&nbsp;Manead Khin ,&nbsp;Timothy R. Dorsey ,&nbsp;Alfredo Lopez Carrero ,&nbsp;Joanna E. Burdette","doi":"10.1016/j.cpt.2024.03.003","DOIUrl":"10.1016/j.cpt.2024.03.003","url":null,"abstract":"<div><h3>Background</h3><div>High-grade serous ovarian cancer (HGSOC) accounts for 70–80% of all ovarian cancer-related deaths. Multiple studies have suggested that the fallopian tube epithelium (FTE) serves as the cell of origin of HGSOC. Phosphatase and tensin homolog (<em>PTEN</em>) is a tumor suppressor and its loss is sufficient to induce numerous tumorigenic changes in FTE, including increased migration, formation of multicellular tumor spheroids (MTSs), and ovarian colonization. In murine oviductal epithelial (MOE) cells (the equivalent of human FTE) loss of <em>PTEN</em> results in the upregulation of transcripts associated with the extracellular matrix, with a specific focus on the elevation of lysyl oxidase-like 2 (<em>LOXL2</em>). Although LOXL2 is known to drive transformation and invasion in solid tumors and is associated with a poor prognosis in ovarian cancer, its specific role in the tumorigenesis of ovarian cancer originating from FTE remains unclear. Therefore, we aim to investigate whether LOXL2 mediates tumorigenesis from the fallopian tube epithelium.</div></div><div><h3>Methods</h3><div>In this study, we utilized clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (CAS9) technology to delete <em>LOXL2</em> in <em>PTEN</em>-deficient MOE cells to understand its role in mediating the oncogenic effects of PTEN loss. In addition, CRISPR-CAS9 was used to delete LOXL2 in OVCAR8 ovarian cancer cells. We monitored the changes in tumorigenic properties, such as migration, invasion, and growth of three-dimensional (3D) spheroids, to assess whether the loss of LOXL2 resulted in any changes.</div></div><div><h3>Results</h3><div>We found that a reduction in LOXL2 expression did not significantly change the migration or invasive capabilities of PTEN-depleted MOE or human ovarian cancer cells. However, we found that a reduction in LOXL2 expression resulted in a significant reduction in 3D MTS formation and survival in both lines.</div></div><div><h3>Conclusions</h3><div>These results reveal for the first time that <em>PTEN</em> loss in FTE cells increases <em>LOXL2</em> expression through downregulation of <em>Pax2</em>, and LOXL2 deletion blocks 3D spheroid formation.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 68-75"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140399558","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}

{"title":"Three-dimensional (3D) augmented reality during Retzius-sparing robot-assisted radical prostatectomy (RS-RARP): First experience","authors":"Silvia Secco ,&nbsp;Alberto Olivero ,&nbsp;Stefano Tappero ,&nbsp;Paolo Dell’Oglio ,&nbsp;Luca Carbonaro ,&nbsp;Alessandro Marando ,&nbsp;Angelo Vanzulli ,&nbsp;Emanuela Bonoldi ,&nbsp;Aldo Massimo Bocciardi ,&nbsp;Antonio Galfano","doi":"10.1016/j.cpt.2024.06.003","DOIUrl":"10.1016/j.cpt.2024.06.003","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 81-84"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054580","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}

{"title":"Biochemical mechanisms and molecular interactions of vitamins in cancer therapy","authors":"Abdullahi T. Aborode ,&nbsp;Isreal A. Onifade ,&nbsp;Mercy M. Olorunshola ,&nbsp;Gladys O. Adenikinju ,&nbsp;Ibude J. Aruorivwooghene ,&nbsp;Adeboboye C. Femi ,&nbsp;Osasere Jude-Kelly Osayawe ,&nbsp;Abraham Osinuga ,&nbsp;Ebenezer A. Omojowolo ,&nbsp;Adekunle F. Adeoye ,&nbsp;Segun Olapade ,&nbsp;Ibrahim O. Adelakun ,&nbsp;Ogundepo D. Moyinoluwa ,&nbsp;Oluwatosin M. Adeyemo ,&nbsp;Godfred Y. Scott ,&nbsp;Ruth A. Ogbonna ,&nbsp;Emmanuel A. Fajemisin ,&nbsp;Omama Ehtasham ,&nbsp;Soyemi Toluwalashe ,&nbsp;Adetolase A. Bakre ,&nbsp;Terungwa H. Iorkula","doi":"10.1016/j.cpt.2024.05.001","DOIUrl":"10.1016/j.cpt.2024.05.001","url":null,"abstract":"<div><div>Recently, the potential role of vitamins in cancer therapy has attracted considerable research attention. However, the reported findings are inconsistent, with limited information on the biochemical and molecular interactions of different vitamins in various cancer cells. Importantly, the presence of vitamin receptors in tumor cells suggests that vitamins play a significant role in the molecular and biochemical interactions in cancers. Additionally, studies on the efficacy of vitamin supplementation and dosage levels on tumor progression and mortality risk have yielded inconsistent results. Notably, molecular and biochemical investigations have reported the function of vitamins in the proliferation, growth, and invasiveness of tumor cells, as well as in cell cycle arrest and inflammatory signaling. Additionally, different vitamins may regulate the cancer microenvironment by activating various molecular pathways. Vitamins significantly affect immunological function, antioxidant defense, inflammation, and epigenetic control, and can improve treatment outcomes by affecting cell behavior and combating stress and DNA damage. However, further research is necessary to confirm the efficacy of vitamins, establish ideal dosages, and develop effective cancer prevention and treatment plans. Individualized supplementation plans guided by medical knowledge are crucial to achieving optimal results in clinical and preclinical settings. In this review, we critically evaluated the effects of different vitamins on the risk and development of cancer. Additionally, we examined the potential of vitamin supplements to enhance the efficacy of drug therapy and counteract resistance mechanisms that often arise during cancer treatment.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 3-15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141030686","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}

{"title":"Integrative analysis of cuproptosis-related lncRNAs: Unveiling prognostic significance, immune microenvironment, and copper-induced mechanisms in prostate cancer","authors":"Haitao Zhong ,&nbsp;Yiming Lai ,&nbsp;Wenhao Ouyang ,&nbsp;Yunfang Yu ,&nbsp;Yongxin Wu ,&nbsp;Xinxin He ,&nbsp;Lexiang Zeng ,&nbsp;Xueen Qiu ,&nbsp;Peixian Chen ,&nbsp;Lingfeng Li ,&nbsp;Jie Zhou ,&nbsp;Tianlong Luo ,&nbsp;Hai Huang","doi":"10.1016/j.cpt.2024.03.004","DOIUrl":"10.1016/j.cpt.2024.03.004","url":null,"abstract":"<div><h3>Background</h3><div>Long non-coding ribonucleic acids (lncRNAs) regulate messenger RNA (mRNA) expression and influence cancer development and progression. Cuproptosis, a newly discovered form of cell death, plays an important role in cancer. Nonetheless, additional research investigating the association between cuproptosis-related lncRNAs and prostate cancer (PCa) prognosis is required.</div></div><div><h3>Methods</h3><div>Sequencing data and copy number variant data were obtained from 492 patients with PCa from The Cancer Genome Atlas (TCGA) Program. Prognostic models of PCa based on cuproptosis-related lncRNAs were constructed using a multi-level attention graph neural network (MLA-GNN) deep learning algorithm. Immune escape scoring was performed using Tumor Immune Dysfunction and Exclusion. Cellular experiments were conducted to explore the correlation between key lncRNAs and cuproptosis.</div></div><div><h3>Results</h3><div>Data from 492 patients with PCa were randomized into two groups at a 1:1 ratio. Prognostic modeling was successfully established using MLA-GNN. Survival analysis suggested that patients could be divided into high- and low-risk groups according to model scores and that there was a significant difference in disease-free survival (DFS) (<em>P</em> &lt; 0.01). The area under the receiver operating characteristic (ROC) curve (AUC) indicated a strong predictive performance for the model, with AUCs of 0.913, 0.847, and 0.863 for the training group and 0.815, 0.907, and 0.866 for the test group at 12, 36, and 60 months, respectively. The immune escape score and immune microenvironment analysis suggested that the high-risk group corresponded to a stronger immune escape and a poorer immune microenvironment (<em>P</em> &lt; 0.05). Cellular experiments revealed that the expression of all six key lncRNAs was upregulated in the presence of copper ion carriers (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>This study identified cuproptosis-related lncRNAs that were strongly associated with PCa prognosis. Key lncRNAs could affect copper metabolism and may serve as new therapeutic targets.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 48-59"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140401211","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}

{"title":"Characteristics and outcomes of secondary acute lymphoblastic leukemia (sALL) after multiple myeloma (MM): SEER data analysis in a single-center institution","authors":"Jing Jia,&nbsp;Jiahui Yin,&nbsp;Chuanying Geng,&nbsp;Aijun Liu","doi":"10.1016/j.cpt.2024.06.007","DOIUrl":"10.1016/j.cpt.2024.06.007","url":null,"abstract":"<div><h3>Background</h3><div>Secondary acute lymphoblastic leukemia (sALL) is rare in patients diagnosed with antecedent multiple myeloma (MM). This study aimed to elucidate the clinical features and outcomes of patients with sALL after MM.</div></div><div><h3>Methods</h3><div>We conducted this population-based study using the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed patients with sALL following MM treatment at our institution. Cox regression analysis was performed to investigate the prognostic factors for survival in patients with sALL.</div></div><div><h3>Results</h3><div>We identified 64,629 cases of MM (including 18 sALL from the SEER Plus 9 database, and three sALL from our institution). Younger patients with MM and those who received chemotherapy were at a higher risk of developing sALL. The novel agent era witnessed an increased incidence of sALL (post-novel agent era <em>vs.</em> pre-novel agent era: 0.31% [10/32,640] <em>vs.</em> 0.25% [8/31,989]) and shorter latency time (post-novel agent era <em>vs.</em> pre-novel agent era [median]: 51.5 <em>vs.</em> 74.5 months, <em>P</em> = 0.516), though the difference was not significant. The median age at sALL onset was 65 (range: 47–78) years. Significant cytopenia and absence of <em>BCR/ABL</em> fusion genes were common features in this patient population. The treatment of sALL is complicated by old age and poor performance status. The median survival of patients with sALL is 18 months, whereas those who received chemotherapy had significantly prolonged survival.</div></div><div><h3>Conclusions</h3><div>Patients with sALL combined with an antecedent MM, especially those with long-term exposure to immunomodulatory agents such as thalidomide or lenalidomide, should be cautiously evaluated and managed with a comprehensive approach.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 76-80"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703803","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}

{"title":"Connecting scientists and oncologists for advances","authors":"Yunlong Yang,&nbsp;Changhao Wu,&nbsp;Wei Zhu","doi":"10.1016/j.cpt.2024.06.006","DOIUrl":"10.1016/j.cpt.2024.06.006","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 1-2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141712445","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}

{"title":"Cover","authors":"","doi":"10.1016/S2949-7132(24)00090-9","DOIUrl":"10.1016/S2949-7132(24)00090-9","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Page OFC"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094499","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}

{"title":"Fecal methylated syndecan-2 (SDC2) testing for early screening of colorectal cancerous and precancerous lesions: A real-world retrospective study in China","authors":"Boyu Qin ,&nbsp;Haitao Niu ,&nbsp;Lupeng Qiu ,&nbsp;Hongfeng Zhou ,&nbsp;Peng Lyu","doi":"10.1016/j.cpt.2024.02.002","DOIUrl":"10.1016/j.cpt.2024.02.002","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is a major public health concern and the second leading cause of cancer-related deaths worldwide. However, challenges remain in deploying effective screening strategies for early-stage CRC. This study aimed to evaluate the effectiveness of a fecal-based syndecan-2 (<em>SDC2</em>) methylation test for the detection of colorectal lesions and CRC.</div></div><div><h3>Methods</h3><div>We retrospectively collected data on participants who underwent fecal <em>SDC2</em> methylation testing from January 1, 2019, to May 30, 2023. Patients with positive results were recommended to undergo colonoscopy. Performance indicators associated with certain clinical characteristics, including positive rate (PR), positive predictive value (PPV), and colonoscopy compliance rate (CCR), were subjected to statistical analysis.</div></div><div><h3>Results</h3><div>We analyzed data from 113,209 participants, of whom 11,841 (10.4% PR) had positive fecal <em>SDC2</em> methylation test results. A total of 4315 participants with positive results adhered to the colonoscopy recommendations, and the CCR was 36.4%. Finally, 3169 colorectal lesions were detected, including 1134 polyps, 875 non-advanced adenomas (NAAs), 770 advanced adenomas (AAs), and 390 CRCs, with PPV values of 26.3% (1134/4315), 20.3% (875/4315), 17.8% (770/4315), and 9.0% (390/4315), respectively. Notably, the PPV for CRC increased significantly with age (<em>χ</em>² = 164.40, <em>P</em> &lt; 0.0001). In addition, as the cycle threshold (CT) values increased, the PPVs of AAs and CRCs generally decreased, whereas those of NAAs and polyps significantly increased. Moreover, the clinical patient group had the highest incidence of late-stage CRC (stage II and higher), whereas asymptomatic populations from the staff physical examination group and rural town-based screening programs had the highest number of stage 0 and I CRCs detected (<em>P</em> = 0.0107).</div></div><div><h3>Conclusions</h3><div>This study indicates that fecal <em>SDC2</em> methylation testing combined with colonoscopy may be an effective screening method for colorectal lesions and CRC.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 60-67"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140467413","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}

{"title":"Despicable role of epithelial–mesenchymal transition in breast cancer metastasis: Exhibiting de novo restorative regimens","authors":"Paras Famta ,&nbsp;Saurabh Shah ,&nbsp;Biswajit Dey ,&nbsp;Kondasingh Charan Kumar ,&nbsp;Deepkumar Bagasariya ,&nbsp;Ganesh Vambhurkar ,&nbsp;Giriraj Pandey ,&nbsp;Anamika Sharma ,&nbsp;Dadi A. Srinivasarao ,&nbsp;Rahul Kumar ,&nbsp;Santosh Kumar Guru ,&nbsp;Rajeev Singh Raghuvanshi ,&nbsp;Saurabh Srivastava","doi":"10.1016/j.cpt.2024.01.001","DOIUrl":"10.1016/j.cpt.2024.01.001","url":null,"abstract":"<div><div>Breast cancer (BC) is the most prevalent cancer in women globally. Anti-cancer advancements have enabled the killing of BC cells through various therapies; however, cancer relapse is still a major limitation and decreases patient survival and quality of life. Epithelial-to-mesenchymal transition (EMT) is responsible for tumor relapse in several cancers. This highly regulated event causes phenotypic, genetic, and epigenetic changes in the tumor microenvironment (TME). This review summarizes the recent advancements regarding EMT using de-differentiation and partial EMT theories. We extensively review the mechanistic pathways, TME components, and various anti-cancer adjuvant and neo-adjuvant therapies responsible for triggering EMT in BC tumors. Information regarding essential clinical studies and trials is also discussed. Furthermore, we also highlight the recent strategies targeting various EMT pathways. This review provides a holistic picture of BC biology, molecular pathways, and recent advances in therapeutic strategies.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 30-47"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139633753","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}

{"title":"Cancer phylogenetic inference using copy number alterations detected from DNA sequencing data","authors":"Bingxin Lu","doi":"10.1016/j.cpt.2024.04.003","DOIUrl":"10.1016/j.cpt.2024.04.003","url":null,"abstract":"<div><div>Cancer is an evolutionary process involving the accumulation of diverse somatic mutations and clonal evolution over time. Phylogenetic inference from samples obtained from an individual patient offers a powerful approach to unraveling the intricate evolutionary history of cancer and provides insights that can inform cancer treatment. Somatic copy number alterations (CNAs) are important in cancer evolution and are often used as markers, alone or with other somatic mutations, for phylogenetic inferences, particularly in low-coverage DNA sequencing data. Many phylogenetic inference methods using CNAs detected from bulk or single-cell DNA sequencing data have been developed over the years. However, there have been no systematic reviews on these methods. To summarize the state-of-the-art of the field and inform future development, this review presents a comprehensive survey on the major challenges in inference, different types of methods, and applications of these methods. The challenges are discussed from the aspects of input data, models of evolution, and inference algorithms. The different methods are grouped according to the markers used for inference and the types of the reconstructed trees. The applications include using phylogenetic inference to understand intra-tumor heterogeneity, metastasis, treatment resistance, and early cancer development. This review also sheds light on future directions of cancer phylogenetic inference using CNAs, including the improvement of scalability, the utilization of new types of data, and the development of more realistic models of evolution.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 1","pages":"Pages 16-29"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140764900","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}