Translational cancer research最新文献

{"title":"<i>CTNND2</i> gene expression in melanoma tissues and its effects on the malignant biological functions of melanoma cells.","authors":"Jiaojiao Qu, Xianfeng Cheng, Mingyan Liu, Qiang Zhang","doi":"10.21037/tcr-24-2159","DOIUrl":"10.21037/tcr-24-2159","url":null,"abstract":"<p><strong>Background: </strong>The catenin delta 2 (<i>CTNND2</i>) gene has been implicated in the progression of various cancers, but its specific role in melanoma has not yet been thoroughly investigated. This study sought to explore the expression and biological function of <i>CTNND2</i> in malignant melanoma tissues to identify new targets or biomarkers for melanoma diagnosis and treatment.</p><p><strong>Methods: </strong>Immunohistochemistry was used to examine the levels of <i>CTNND2</i> in melanoma and adjacent non-tumor tissues. A Western blot analysis was performed to quantify the expression levels of <i>CTNND2</i> in human immortalized keratinocytes and melanoma cell lines. The Cell Counting Kit-8 (CCK-8) assay, plate colony formation assay, cell adhesion assay, scratch test, and Transwell assay were used to assess the effects of <i>CTNND2</i> knockdown on the proliferation, adhesion, migration, and invasion of melanoma cells. The Harmonizome database was used to research the biological processes (BPs) involved in <i>CTNND2</i>.</p><p><strong>Results: </strong>In the melanoma tissues, <i>CTNND2</i> expression was substantially upregulated and its levels were closely linked with the pathological features of patients. The <i>CTNND2</i> levels were notably more increased in the melanoma cell lines than the immortalized keratinocytes. The suppression of the <i>CTNND2</i> gene substantially impeded the capacity of the melanoma cells to proliferate, migrate, and invade, and also significantly decreased their potential to attach to collagen I and IV, and fibronectin. The Harmonizome database results revealed a strong correlation between the BPs controlled by <i>CTNND2</i> and the focal adhesion signaling pathway of the cells. The inhibition of the <i>CTNND2</i> gene in melanoma cells resulted in a significant decrease in the phosphorylation of focal adhesion kinase (FAK) and the production of paxillin protein. In the melanoma cells, the reduction of <i>CTNND2</i> did not have a significant effect on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. However, it did considerably prevent the activation of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and its downstream molecule extracellular signal-regulated protein kinase 1/2 (ERK1/2).</p><p><strong>Conclusions: </strong>The expression of the <i>CTNND2</i> gene is increased in melanoma tissues, which enhances the ability of melanoma cells to proliferate both <i>in vivo</i> and <i>in vitro</i>. Additionally, the <i>CTNND2</i> gene is crucial in controlling the adhesion process of melanoma cells. This mechanism is associated with the regulation of the FAK and MEK1/2/ERK1/2 signaling pathways. Based on our findings, <i>CTNND2</i> could be used as an oncogene target for melanoma and a new treatment target or diagnostic biomarker.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6347-6363"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative clinical trials review in the realm of focal therapy for localized prostate cancer.","authors":"Alon Lazarovich, Vijay Viswanath, Aaron S Dahmen, Abhinav Sidana","doi":"10.21037/tcr-23-2406","DOIUrl":"10.21037/tcr-23-2406","url":null,"abstract":"<p><strong>Background and objective: </strong>The role of focal therapy in the treatment of localized prostate cancer is evolving. However, despite accumulating evidence, current guidelines and regulatory bodies refrain from endorsing focal therapy outside of clinical trials. Our goal was the to review the focal therapy realm for ongoing clinical trials and high impact recently published trials.</p><p><strong>Methods: </strong>Our comprehensive investigation includes an exhaustive review of ClinicalTrials.gov and PubMed databases, identifying and analyzing clinical trials with diverse modalities of focal therapy. In this review, we focused on critical ongoing and recently concluded clinical trials (2-15-2023) in the focal therapy realm.</p><p><strong>Key content and findings: </strong>We identified several trials on focal therapy at various stages of progression and various trial design. The trials study all different modalities of focal therapy including high-intensity focused ultrasound (HIFU), cryoablation, irreversible electroporation (IRE), focal laser ablation (FLA), transurethral ultrasound ablation (TULSA)-PRO^®, and Water Vapor ablation. The trials focus both on oncological outcomes and quality of life outcomes. Novel clinical trials study the additive impact of androgen deprivation therapy (ADT) to different focal therapy modalities.</p><p><strong>Conclusions: </strong>The exploration of focal therapy in prostate cancer holds promise for achieving oncological control while minimizing the impact on patients' quality of life. Continued research and trial results will play a pivotal role in delineating focal therapy's optimal role in the broader prostate cancer treatment spectrum.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6529-6539"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroepithelial cell transforming 1 as a key regulator in non-small cell lung cancer: unveiling causal links and therapeutic potentials.","authors":"Xiaoqing Shangguan, Xinping Zhang, Xiwu Chen, Zheng Zhang, Lei Wang","doi":"10.21037/tcr-24-587","DOIUrl":"10.21037/tcr-24-587","url":null,"abstract":"<p><strong>Background: </strong>High incidence and mortality rates underscore lung cancer as a significant global health issue. Understanding the molecular mechanisms driving its progression is crucial for developing effective treatments. This study explores a potential molecular regulator that may contribute to the progression of non-small cell lung cancer (NSCLC) by utilizing bioinformatics analyses and laboratory experiments, aiming to provide insights that could inform future therapeutic strategies.</p><p><strong>Methods: </strong>Our research combined single-cell RNA sequencing (scRNA-seq) data analysis with the Mendelian randomization (MR) algorithm. MR analysis using genetic variants associated with NSCLC risk aimed to uncover causal relationships between genes and cancer traits. To validate the impact of neuroepithelial cell transforming 1 (<i>NET1</i>) on cellular proliferation and its role in inhibiting ferroptosis, we utilized quantitative real-time polymerase chain reaction (qRT-PCR), cell viability assays, and malondialdehyde (MDA) detection. Furthermore, molecular docking analyses of four compounds demonstrated their potential in modulating the downregulation of <i>NET1</i>.</p><p><strong>Results: </strong>ScRNA-seq exposed cellular diversity in non-malignant lungs and tumors. Distinct expression patterns in epithelial cells and identified gene pathways pointed to cell proliferation. <i>NET1</i>, causally linked to NSCLC through MR analysis, showed increased expression in tumors and correlated with unfavorable overall survival, validated by functional assays. Utilizing cell viability assays and MDA detection, our results validated the pivotal role of <i>NET1</i> in enhancing cellular proliferation and its efficacy in inhibiting ferroptosis. Doxorubicin, piroxicam, and quercetin emerged as potential drug candidates for NSCLC treatment based on molecular docking analysis.</p><p><strong>Conclusions: </strong>Our findings confirm <i>NET1</i>'s significant role in NSCLC progression, influencing cell proliferation, ferroptosis, immune activity regulation and identify potential therapeutics for targeted lung cancer treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6087-6104"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bladder sparing management for muscle-invasive bladder cancer after a complete clinical response: ready for prime time?-a narrative review.","authors":"Mann Patel, Kyle Moore, Benjamin L Lichtbroun, Ryan D Stephenson, Tina Mayer, Biren Saraiya, David Golombos, Thomas Jang, Vignesh T Packiam, Saum Ghodoussipour","doi":"10.21037/tcr-24-726","DOIUrl":"10.21037/tcr-24-726","url":null,"abstract":"<p><strong>Background and objective: </strong>A standard of care for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Given recent improvements in NAC and the morbidity associated with RC, bladder-sparing therapy has been investigated as a promising treatment for patients with MIBC who experience a complete clinical response (CCR) to systemic therapy. However, clinical staging is unreliable, making it challenging to determine ideal candidates for bladder-sparing therapy. Our primary objective is to review the efficacy of NAC, strategies for determining a CCR as a surrogate for a complete pathologic response, and the emerging role of imaging, tumor genomics, and biomarkers in selecting candidates for bladder-sparing therapy.</p><p><strong>Methods: </strong>We surveyed the literature for studies investigating the outcomes of current treatment modalities for MIBC and methods for determining a CCR following systemic therapy as well as the impact this has on pathologic staging. Studies employing imaging, tumor biomarkers, and genomics were included.</p><p><strong>Key content and findings: </strong>Clinical staging with cystoscopy or transurethral resection shows significant discordance with final pathology, with high rates of understaging. Multiparametric magnetic resonance imaging (mpMRI) has shown strong utility in determining the presence of MIBC, but it has yet to reliably identify CCR. Meanwhile, somatic DNA damage repair mutations and biomarkers such as circulating and urinary tumor DNA are strong predictors of recurrence, showing promise in predicting and monitoring a CCR to systemic therapy. Multiple ongoing trials are currently assessing the use of biomarkers and genomic analyses in determining eligibility for bladder-sparing therapy.</p><p><strong>Conclusions: </strong>While no one method has reliably demonstrated the ability to detect a true CCR, a multimodal approach involving imaging, biomarkers, and genomic analyses holds promise. We eagerly await the results of clinical trials investigating these tools, which may allow for the safe recommendation of bladder-sparing therapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6413-6429"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential role of TWIST1 and its methylation in bladder urothelial carcinoma.","authors":"Meixuan Wan, Hongxue Meng, Huining Li","doi":"10.21037/tcr-24-1029","DOIUrl":"10.21037/tcr-24-1029","url":null,"abstract":"<p><strong>Background: </strong>Bladder urothelial carcinoma (BLCA), like other cancers, is strongly associated with genetic and epigenetic changes. TWIST1 is an epithelial-mesenchymal transition (EMT) promoter that has been linked to the development of many malignancies. It is still unclear, however, what role TWIST1 plays in BLCA, and the relationship between TWIST1 transcript levels and its promoter methylation and immune infiltration has been reported even less. This study aimed to reveal the potential role of TWIST1 promoter methylation-related changes in BLCA.</p><p><strong>Methods: </strong>Transcriptional expression data of TWIST1 in BLCA were acquired from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and University of Alabama at Birmingham (UALCAN) databases. TWIST1 methylation levels and prognosis were sourced from Gene Expression Profiling Interactive Analysis 2 (GEPIA2), LinkedOmics, cBio Cancer Genomics Portal (c-BioPortal), MethSurv, and DNA Methylation Information Visualization Database (DNMIVD) databases. The methylation status of the BLCA-associated TWIST1 in preoperative and postoperative urinary exfoliated cells was subsequently analyzed using methylation-specific real-time fluorescence polymerase chain reaction, with validation of accuracy through pyrophosphate sequencing. Finally, from the Gene Set Cancer Analysis (GSCA) and Tumor-Immune System Interaction Database (TISIDB) databases, we obtained the association between TWIST1 transcript expression and DNA methylation and cancer immune infiltration and immunolabelling.</p><p><strong>Results: </strong>Our study demonstrated that TWIST1 expression was down-regulated in BLCA, which was negatively correlated with DNA methylation. The association between TWIST1 promoter hypermethylation and the progression, staging, grading, and recurrence of BLCA is highly significant. Furthermore, we revealed that hypermethylation of both the preoperative and postoperative TWIST1 promoters is useful as a biomarker for monitoring BLCA recurrence, particularly when considering the methylation status of specific CpG sites. Additionally, we observed that TWIST1 expression, promoter methylation, and immune infiltration immunoreactive markers correlated significantly in BLCA.</p><p><strong>Conclusions: </strong>We propose that TWIST1 holds great promise as a diagnostic and therapeutic target for BLCA, with the potential to influence tumor progression and patient prognosis through the regulation of immune cell infiltration. We hope these findings contribute valuable insights to the field of BLCA research.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6070-6086"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging functions of FMNL1 in myeloid neoplasms: insights from bioinformatics to biological and pharmacological landscapes.","authors":"João Agostinho Machado-Neto, Hugo Passos Vicari, Jean Carlos Lipreri da Silva, Maria Fernanda Lopes Carvalho, Keli Lima","doi":"10.21037/tcr-24-1091","DOIUrl":"10.21037/tcr-24-1091","url":null,"abstract":"<p><strong>Background: </strong>Myeloid neoplasms encompass disorders characterized by abnormal myeloid cell proliferation and differentiation, including myelodysplastic syndromes (MDS), myeloproliferative neoplasms, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Formin-like protein 1 (FMNL1) is involved in the regulation of the actin cytoskeleton and is predominantly expressed in hematopoietic cells. Given its role in leukemia cell proliferation, survival, migration, and invasion, this study investigates FMNL1 expression in normal hematopoiesis and myeloid neoplasms and explores associations with clinical-laboratory characteristics, mutational status, and survival outcomes in AML.</p><p><strong>Methods: </strong>Transcript levels of <i>FMNL1</i> from several blood-forming cell populations and myeloid neoplasms were extracted from publicly available databases. Myeloid neoplasm cell lines were used for gene/protein expression and cell differentiation studies. Functional genomics analysis was performed using RNA-seq data from The Cancer Genome Atlas (TCGA) AML study, and drug sensitivity predictions were investigated using Beat AML and Genomics of Drug Sensitivity in Cancer (GDSC) datasets. Statistical analyses assessed the impact of <i>FMNL1</i> expression on clinical outcomes.</p><p><strong>Results: </strong>FMNL1 was highly expressed in metamyelocytes, neutrophils, and monocytes compared to hematopoietic stem cells, and its expression increased with granulocytic differentiation. FMNL1 expression was elevated in AML and CML patients compared to healthy donors. <i>FMNL1</i> expression was not significantly associated with clinical-laboratory characteristics or survival outcomes but showed a higher frequency of WT1 transcription factor (WT1) mutations with low <i>FMNL1</i> expression in AML patients. High FMNL1 expression in AML correlated with immune response and inflammatory activity pathways. <i>FMNL1</i> mRNA levels influenced drug sensitivity in AML models, with correlations observed for specific antineoplastic agents.</p><p><strong>Conclusions: </strong>FMNL1 plays a potential role in granulocyte differentiation and function, and its differential expression is linked to critical signaling pathways in leukemogenesis and inflammation. These findings highlight FMNL1's potential therapeutic implications in myeloid neoplasia, warranting further investigation.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6105-6116"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting C797S mutations and beyond in non-small cell lung cancer-a mini-review.","authors":"Wolfram C M Dempke, Klaus Fenchel","doi":"10.21037/tcr-24-690","DOIUrl":"10.21037/tcr-24-690","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer cases and has a high mortality worldwide, however, targeting common epidermal growth-factor receptor (EGFR) alterations (i.e., del19, L858R) has provided a paradigm shift in the treatment of NSCLC. Uncommon EGFR mutations, however, show variable efficacy to EGFR-targeted drugs depending on the molecular alterations within exons 18-21 which underlying biological mechanism are far from being clear. The substitution mutations of G719X in exon 18, L861Q in exon 21, S768I in exon 20, and exon 20 insertions are the most frequent mutations among the uncommon mutations. The development of fourth-generation EGFR-tyrosine kinase inhibitor (TKIs) has gained increased interest as these drugs are able to inhibit resistance mutations (e.g., C797S) often detected in NSCLC patients' resistance to third-generation EGFR TKIs. BDTX-1535 is an orally bioavailable, brain-penetrating, mutation-selective, irreversible EGFR inhibitor with significant antitumour activity in NSCLCs and glioblastomas (phase I/II trials ongoing). It is a fourth-generation EGFR inhibitor that was found to overcome resistance to osimertinib in preclinical models and has shown promising activity in NSCLC patients harbouring C797S mutations. In experimental models BDTX-1535 was found to inhibit all common EGFR mutations and more than 50 of uncommon mutations including T790M, C797S, L718X, E709X, S784F, V834L and A289V, however, exon 20 insertions are inhibited to a much lesser extent. In addition, mutations in the extracellular domain of the EGF receptor (e.g., EGFRvII, III, IV) can be blocked as well. It should be noted that in up to 50% of all NSCLC patients who progress following osimertinib or other EGFR TKI therapy no underlying resistance mechanism can be identified suggesting that non-mutational signal transduction pathways may also be operative, and intratumoural heterogeneity has been found to be a major contributor to resistance and it consists of three main mechanisms: (I) drug-tolerant persister (DTP) cells, (II) chromosomal instability, and (III) extrachromosomal extracellular DNA (ecDNA) (seen in over 50% of NSCLCs) suggesting that novel EGFR TKIs will include many challenges in sufficiently targeting on-target resistance mechanisms. The development of novel drugs that can overcome TKI resistance in NSCLC patients harbouring the C797S mutation and beyond is, therefore, eagerly warranted.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6540-6549"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant phyllodes tumor of the breast with bilateral ductal carcinoma in situ and postoperative distant metastasis: a case report.","authors":"Hongyu Liu, Bin Wang, Yuxingzi Chen","doi":"10.21037/tcr-24-497","DOIUrl":"10.21037/tcr-24-497","url":null,"abstract":"<p><strong>Background: </strong>Phyllodes tumors (PTs) are breast neoplasms with varying degrees of malignancy, posing challenges in diagnosis and management. This case report focuses on a rare case of malignant phyllodes tumor of the breast (MPTB) in a 35-year-old woman.</p><p><strong>Case description: </strong>This case report presents a complex scenario of a patient with extensive breast abnormalities, including a malignant PT in the left breast, ductal carcinoma <i>in situ</i> in both breasts, with axillary lymph node involvement. Radiological examinations revealed multiple masses with varying characteristics, leading to a challenging diagnosis. Considering a huge malignant breast tumor, surgery was suggested immediately without biopsy. Surgical intervention, including modified radical mastectomy, was performed, and pathological findings diagnosed of malignant PT with intraductal carcinoma. The patient experienced disease progression shortly after surgery, with metastases detected in the left axillary lymph node and both lungs at the third month after discharge. Despite further treatment is suggested, the patient refused the treatment options. The patient's condition rapidly deteriorated, leading to her unfortunate demise four months after surgery.</p><p><strong>Conclusions: </strong>This case accentuates the complex nature of MPTB, highlighting the urgent need for seeking medical attention promptly, sufficient preoperative assessment, improved diagnostic techniques, interdisciplinary collaboration, and advanced treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6576-6583"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant therapy in renal cell carcinoma (RCC): progress, at last.","authors":"Andrew N Bueno, Mark N Stein, Karie Runcie","doi":"10.21037/tcr-23-2247","DOIUrl":"10.21037/tcr-23-2247","url":null,"abstract":"<p><p>In the United States, there is expected to be about 82,000 cases of renal cell carcinoma (RCC) in 2024. At diagnosis, approximately 65% of patients with RCC will have disease localized to the kidney. For decades, the standard of care for patients with localized RCC has been surgery, which is often curative, followed by radiographic surveillance. However, after nephrectomy, patients may have up to 50% risk of recurrence. Thus, there has been a longstanding effort to reduce the recurrence of kidney cancer in the adjuvant setting after nephrectomy and/or metastasectomy. Over the past 30 years, a number of different therapeutic agents have been tested in the adjuvant setting including cytokines, autologous tumor cell vaccines, vascular endothelial growth factor (VEGF) pathway inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and most recently immune checkpoint inhibitors (ICIs). The vast majority of these adjuvant trials in RCC have shown no significant clinical benefit for patients. In 2021, the KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab improved progression-free survival and more recently showed an overall survival benefit for patients with high risk of recurrence of clear cell RCC (ccRCC). These findings have ushered in a new standard of care for patients with ccRCC at high risk of recurrence after nephrectomy. Here, we provide an overview of the major adjuvant trials in RCC, with a focus on ccRCC, and provide a framework for the management of patients with high risk localized ccRCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6448-6462"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic analysis of SYTL4 in acute myeloid leukemia.","authors":"Kun-Ying Xie, Jin Wei","doi":"10.21037/tcr-24-758","DOIUrl":"10.21037/tcr-24-758","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. The key problem lies in the complexity of the genome, so that drug resistance and relapse have become the main problems. Recent studies have found an association between synaptotagmin-like 4 (SYTL4) and drug resistance in triple-negative breast cancer and its high expression is correlated with poor prognosis; however, it is unclear whether this gene is associated with the prognosis of AML. This study aimed to investigate the role and action mechanism of SYTL4 in AML.</p><p><strong>Methods: </strong>We downloaded gene expression profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA) public database and conducted differential and survival analyses using the Limma and survival packages in R. The receiver operating characteristic (ROC) curve, univariate COX, and multivariate COX were used for gene prediction analysis. Co-expression analysis of SYTL4 was performed using Limma, and enrichment analysis of differentially expressed genes in the SYTL4 high- and low-expression groups was conducted. We performed immune cell infiltration using the CIBERSORTx algorithm.</p><p><strong>Results: </strong>The expression level of SYTL4 was highest in the poor prognosis group, and lowest in the good prognosis group. Survival was better in the SYTL4 low expression group than that in the high expression group. The areas under the ROC curve for TCGA-Acute Myeloid Leukemia (TCGA-LAML) at 1, 3, and 5 years were 0.725, 0.683, and 0.787, respectively. Sushi repeat protein X-linked 2 (SRPX2), caveolae associated protein 2 (CAVIN2), and other genes were identified as positive regulators of SYTL4 expression, whereas lactoperoxidase (LPO), diacylglycerol lipase beta (DAGLB), and other genes were identified as negative regulators. Differentially expressed genes in the SYTL4 high- and low-expression groups were enriched in pathways such as the embryonic skeletal system and platelet alpha granules. Differences were observed in follicular helper T cells, Tregs, monocytes, and M2 macrophages between SYTL4 high- and low-expression groups.</p><p><strong>Conclusions: </strong>SYTL4 expression negatively correlates with AML prognosis and may be associated with exosome secretion in AML.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"5995-6003"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}