Translational Oncology最新文献_第2页

Unraveling the mechanisms of RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway 揭示 RECQL4 通过 PI3K/AKT 通路介导宫颈癌进展的机制。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-07 DOI: 10.1016/j.tranon.2024.102146

{"title":"Unraveling the mechanisms of RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway","authors":"","doi":"10.1016/j.tranon.2024.102146","DOIUrl":"10.1016/j.tranon.2024.102146","url":null,"abstract":"<div><h3>Background</h3><div>RECQL4 is a member of the DNA helicase family and is critical for DNA replication, DNA damage repair, and tumor progression. However, its specific role in cervical cancer remains uncertain.</div></div><div><h3>Methods</h3><div>In this study, we aimed to investigate the impact of RECQL4 on cervical cancer prognosis using clinical specimens from The Cancer Genome Atlas. We evaluated the malignant effects of RECQL4 through various experimental assays including cell Cell Counting Kit-8, EdU, colony formation, cell cycle analysis, cell apoptosis, scratch, and Transwell assays. We explored the mechanisms of RECQL4-regulated malignancy using analyses of bioinformatics, RNA sequencing data, polymerase chain reaction (PCR), western blotting, and cell immunofluorescence experiments. Furthermore, we validated the effects of RECQL4 knockdown on tumor growth using subcutaneous tumor models in nude mice.</div></div><div><h3>Results</h3><div>RECQL4 was upregulated in cervical cancer and correlated with prognosis, demonstrating a positive relationship with tumor mutational burden. Knockdown of RECQL4 inhibits cervical cancer cell proliferation, migration, and invasion, suppresses epithelial-mesenchymal transition status, induces cell cycle arrest, and promotes apoptosis. Mechanistically, RECQL4 mediated malignancy through the PI3K/AKT pathway and reduced nuclear β-catenin expression. In vivo studies further confirmed that RECQL4 knockout significantly inhibited tumor growth.</div></div><div><h3>Conclusions</h3><div>Our findings provide novel insights into the mechanism behind RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway. Furthermore, our study suggests potential therapeutic strategies for targeting RECQL4 in cervical cancer treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393559","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}

引用次数: 0

The PIK3CA gene and its pivotal role in tumor tropism of triple-negative breast cancer PIK3CA 基因及其在三阴性乳腺癌肿瘤滋养过程中的关键作用。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-05 DOI: 10.1016/j.tranon.2024.102140

{"title":"The PIK3CA gene and its pivotal role in tumor tropism of triple-negative breast cancer","authors":"","doi":"10.1016/j.tranon.2024.102140","DOIUrl":"10.1016/j.tranon.2024.102140","url":null,"abstract":"<div><div>The <em>PIK3CA</em> gene is a linchpin in the intricate molecular network governing triple-negative breast cancer (TNBC) tumor tropism, serving as a focal point for understanding this aggressive disease. Anchored within the PI3K/AKT/mTOR signaling axis, <em>PIK3CA</em> mutations exert substantial influence, driving cellular processes that highlight the unique biology of TNBC. This review meticulously highlights the association between <em>PIK3CA</em> mutations and distinct TNBC subtypes, elucidating the gene's multifaceted contributions to tumor tropism. Molecular dissection reveals how <em>PIK3CA</em> mutations dynamically modulate chemokine responses, growth factor signaling, and extracellular matrix interactions, orchestrating the complex migratory behaviour characteristic of TNBC cells. A detailed exploration of <em>PIK3CA</em>-targeted strategies in the therapeutic arena is presented, outlining the current landscape of clinical trials and precision medicine approaches. As the scientific narrative converges, this review underscores the critical role of <em>PIK3CA</em> in shaping the molecular intricacies of TNBC tumor tropism and illuminates pathways toward tailored interventions, promising a paradigm shift in the clinical management of TNBC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381707","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}

引用次数: 0

Dronedarone hydrochloride inhibits gastric cancer proliferation in vitro and in vivo by targeting SRC 盐酸决奈达隆通过靶向 SRC 在体外和体内抑制胃癌增殖。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-05 DOI: 10.1016/j.tranon.2024.102136

{"title":"Dronedarone hydrochloride inhibits gastric cancer proliferation in vitro and in vivo by targeting SRC","authors":"","doi":"10.1016/j.tranon.2024.102136","DOIUrl":"10.1016/j.tranon.2024.102136","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is a significant global concern, ranking as the fifth most prevalent cancer. Unfortunately, the five-year survival rate is less than 30 %. Additionally, approximately 50 % of patients experience a recurrence or metastasis. As a result, finding new drugs to prevent relapse is of utmost importance.</div></div><div><h3>Methods</h3><div>The inhibitory effect of Dronedarone hydrochloride (DH) on gastric cancer cells was examined using proliferation assays and anchorage-dependent assays. The binding of DH with SRC was detected by molecular docking, pull-down assays, and cellular thermal shift assays (CETSA). DH's inhibition of Src kinase activity was confirmed through <em>in vitro</em> kinase assays. The SRC knockout cells, established using the CRISPR-Cas9 system, were used to verify Src's role in GC cell proliferation. Patient-derived xenograft (PDX) models were employed to elucidate that DH suppressed tumor growth <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Our research discovered DH inhibited GC cell proliferation <em>in vitro</em> and <em>in vivo</em>. DH bound to the SRC protein to inhibit the SRC/AKT1 signaling pathway in gastric cancer. Additionally, we observed a decrease in the sensitivity of gastric cancer cells to DH upon down-regulation of SRC. Notably, we demonstrated DH's anti-tumor effects were similar to those of Dasatinib, a well-known SRC inhibitor, in GC patient-derived xenograft models.</div></div><div><h3>Conclusion</h3><div>Our research has revealed that Dronedarone hydrochloride, an FDA-approved drug, is an SRC inhibitor that can suppress the growth of GC cells by blocking the SRC/AKT1 signaling pathway. It provides a scientific basis for use in the clinical treatment of GC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381706","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}

引用次数: 0

Spatial heterogeneity of infiltrating immune cells in the tumor microenvironment of non-small cell lung cancer 非小细胞肺癌肿瘤微环境中浸润免疫细胞的空间异质性。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-03 DOI: 10.1016/j.tranon.2024.102143

{"title":"Spatial heterogeneity of infiltrating immune cells in the tumor microenvironment of non-small cell lung cancer","authors":"","doi":"10.1016/j.tranon.2024.102143","DOIUrl":"10.1016/j.tranon.2024.102143","url":null,"abstract":"<div><div>Tumor-infiltrating lymphocytes (TILs) are essential components of the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Still, it is difficult to describe due to their heterogeneity. In this study, five cell markers from NSCLC patients were analyzed. We segmented tumor cells (TCs) and TILs using Efficientnet-B3 and explored their quantitative information and spatial distribution. After that, we simulated multiplex immunohistochemistry (mIHC) by overlapping continuous single chromogenic IHCs slices. As a result, the proportion and the density of programmed cell death-ligand 1 (PD-L1)-positive TCs were the highest in the core. CD8+ T cells were the closest to the tumor (median distance: 41.71 μm), while PD-1+T cells were the most distant (median distance: 62.2μm), and our study found that most lymphocytes clustered together within the peritumoral range of 10-30 μm where cross-talk with TCs could be achieved. We also found that the classification of TME could be achieved using CD8+ T-cell density, which is correlated with the prognosis of patients. In addition, we achieved single chromogenic IHC slices overlap based on CD4-stained IHC slices. We explored the number and spatial distribution of cells in heterogeneous TME of NSCLC patients and achieved TME classification. We also found a way to show the co-expression of multiple molecules economically.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376088","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}

引用次数: 0

Near-infrared photoimmunotherapy for osteosarcoma targeting epidermal growth factor receptor 针对表皮生长因子受体的骨肉瘤近红外光免疫疗法

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-01 DOI: 10.1016/j.tranon.2024.102132

{"title":"Near-infrared photoimmunotherapy for osteosarcoma targeting epidermal growth factor receptor","authors":"","doi":"10.1016/j.tranon.2024.102132","DOIUrl":"10.1016/j.tranon.2024.102132","url":null,"abstract":"<div><div>Osteosarcoma is the most common bone tumor, and it possesses high metastatic propensity. Although systemic chemotherapy has improved its prognosis, improvements in survival rates have stalled in recent years. Moreover, the prognosis of patients with metastatic osteosarcoma remains poor. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer therapy that induces immunogenic cell death (ICD), and the therapeutic effects spread to distant metastatic sites. Therefore, NIR-PIT could be useful in both primary and metastatic osteosarcoma treatment. In this study, we investigated the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) in osteosarcoma. The cytotoxic effects of NIR-PIT in osteosarcoma cell lines with different EGFR expression levels (MG63; high, Saos-2; low) were evaluated. NIR-PIT–induced cell death was dependent on the EGFR expression level. After NIR-PIT, swelling and bleb formation, the characteristic morphological changes induced by NIR-PIT associated with necrosis caused by the influx of extracellular fluid, were observed. In addition, the release of the ICD markers lactate dehydrogenase and ATP was detected after NIT-PIT. NIR-PIT significantly suppressed tumor growth in tumor-bearing mice. This study revealed that NIR-PIT targeting EGFR has therapeutic effects and induces ICD in osteosarcoma; thus, it is potentially a novel therapeutic strategy for primary and metastatic osteosarcoma.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366578","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}

引用次数: 0

Highlighting function of Wnt signalling in urological cancers: Molecular interactions, therapeutic strategies, and (nano)strategies 强调 Wnt 信号在泌尿系统癌症中的功能：分子相互作用、治疗策略和（纳米）策略

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-01 DOI: 10.1016/j.tranon.2024.102145

{"title":"Highlighting function of Wnt signalling in urological cancers: Molecular interactions, therapeutic strategies, and (nano)strategies","authors":"","doi":"10.1016/j.tranon.2024.102145","DOIUrl":"10.1016/j.tranon.2024.102145","url":null,"abstract":"<div><div>Cancer is a complex, multistep process characterized by abnormal cell growth and metastasis as well as the capacity of the tumor cells in therapy resistance development. The urological system is particularly susceptible to a group of malignancies known as urological cancers, where an accumulation of genetic alterations drives carcinogenesis. In various human cancers, Wnt singalling is dysregulated; following nuclear transfer of β-catenin, it promotes tumor progression and affects genes expression. Elevated levels of Wnt have been documented in urological cancers, where its overexpression enhances growth and metastasis. Additionally, increased Wnt singalling contributes to chemoresistance in urological cancers, leading to reduced sensitivity to chemotherapy agents like cisplatin, doxorubicin, and paclitaxel. Wnt upregulation can change radiotherapy response of urological cancers. The regulation of Wnt involves various molecular pathways, including Akt, miRNAs, lncRNAs, and circRNAs, all of which play roles in carcinogenesis. Targeting and silencing Wnt or its associated pathways can mitigate tumorigenesis in urological cancers. Anti-cancer compounds such as curcumin and thymoquinone have shown efficacy in suppressing tumorigenesis through the downregulation of Wnt singalling. Notably, nanoparticles have proven effective in treating urological cancers, with several studies in prostate cancer (PCa) using nanoparticles to downregulate Wnt and suppress tumor growth. Future research should focus on developing small molecules that inhibit Wnt singalling to further suppress tumorigenesis and advance the treatment of urological cancers. Moreover, Wnt can be used as reliable biomarker for the diagnosis and prognosis of urological cancers.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359655","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}

引用次数: 0

Transient-resting culture after activation enhances the generation of CD8+ stem cell-like memory T cells from peripheral blood mononuclear cells 活化后的瞬时静止培养可促进外周血单核细胞产生 CD8+ 干细胞样记忆 T 细胞

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-01 DOI: 10.1016/j.tranon.2024.102138

{"title":"Transient-resting culture after activation enhances the generation of CD8+ stem cell-like memory T cells from peripheral blood mononuclear cells","authors":"","doi":"10.1016/j.tranon.2024.102138","DOIUrl":"10.1016/j.tranon.2024.102138","url":null,"abstract":"<div><div>Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (T<sub>SCM</sub>) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. T<sub>SCM</sub> cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8<sup>+</sup> T<sub>SCM</sub> cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion <em>in vitro</em> with interlukien-2. We report that this transient-resting culture after activation preserves CD8<sup>+</sup> T cells in a stem memory phenotype (CD95<sup>+</sup> CD45RA<sup>+</sup> CCR7<sup>+</sup>) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8<sup>+</sup> T<sub>SCM</sub> cells <em>ex vivo</em>. This approach streamlines the optimization of cancer immunotherapy using ACT.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359650","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}

引用次数: 0

GDF15 and LCN2 for early detection and prognosis of pancreatic cancer 用于胰腺癌早期检测和预后判断的 GDF15 和 LCN2

IF 5 2区医学

Translational Oncology Pub Date : 2024-09-30 DOI: 10.1016/j.tranon.2024.102129

{"title":"GDF15 and LCN2 for early detection and prognosis of pancreatic cancer","authors":"","doi":"10.1016/j.tranon.2024.102129","DOIUrl":"10.1016/j.tranon.2024.102129","url":null,"abstract":"<div><h3>Background</h3><div>The prognosis of pancreatic ductal adenocarcinomas (PDAC) remains very poor, emphasizing the critical importance of early detection, where biomarkers offer unique potential. Although growth differentiation factor 15 (GDF15) and Lipocalin 2 (LCN2) have been linked to PDAC, their precise roles as biomarkers are uncertain.</div></div><div><h3>Methods</h3><div>Circulating levels of GDF15 and LCN2 were examined in human PDAC patients, heathy controls, and individuals with benign pancreatic diseases. Circulating levels of IL-6, CA19-9, and neutrophil-to-lymphocyte ratio (NLR) were measured for comparisons. Correlations between PDAC progression and overall survival were assessed. A mouse PDAC model was employed for comprehensive analyses, complementing the human studies by exploring associations with various metabolic and inflammatory parameters. Sensitivity and specificity of the biomarkers were evaluated.</div></div><div><h3>Findings</h3><div>Our results demonstrated elevated levels of circulating GDF15 and LCN2 in PDAC patients compared to both healthy controls and individuals with benign pancreatic diseases, with higher GDF15 levels associated with disease progression and increased mortality. In PDAC mice, circulating GDF15 and LCN2 progressively increased, correlating with tumor growth, behavioral manifestations, tissue and molecular pathology, and cachexia development. GDF15 exhibited highly sensitive and specific for PDAC patients compared to CA19-9, IL-6, or NLR, while LCN2 showed even greater sensitivity and specificity in PDAC mice. Combining GDF15 and LCN2, or GDF15 and CA19-9, enhanced sensitivity and specificity.</div></div><div><h3>Interpretation</h3><div>Our findings indicate that GDF15 holds promise as a biomarker for early detection and prognosis of PDAC, while LCN2 could strengthen diagnostic panels.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359654","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}

引用次数: 0

Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor 支气管冲洗液测序有助于诊断伴有坏死肿瘤的肺癌

IF 5 2区医学

Translational Oncology Pub Date : 2024-09-30 DOI: 10.1016/j.tranon.2024.102134

{"title":"Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor","authors":"","doi":"10.1016/j.tranon.2024.102134","DOIUrl":"10.1016/j.tranon.2024.102134","url":null,"abstract":"<div><h3>Background</h3><div>Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach.</div></div><div><h3>Methods</h3><div>From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified.</div></div><div><h3>Results</h3><div>Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %.</div></div><div><h3>Conclusions</h3><div>BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359656","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}

引用次数: 0

Surgery, chemoradiotherapy, or chemoradiation plus immunotherapy: Treatment strategies for nonmetastatic anal squamous cell carcinoma 手术、化放疗或化放疗加免疫疗法：非转移性肛门鳞状细胞癌的治疗策略

IF 5 2区医学

Translational Oncology Pub Date : 2024-09-30 DOI: 10.1016/j.tranon.2024.102133

{"title":"Surgery, chemoradiotherapy, or chemoradiation plus immunotherapy: Treatment strategies for nonmetastatic anal squamous cell carcinoma","authors":"","doi":"10.1016/j.tranon.2024.102133","DOIUrl":"10.1016/j.tranon.2024.102133","url":null,"abstract":"<div><div>The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, <em>P</em> < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, <em>P</em> = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, <em>P</em> < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ <em>T</em> cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359652","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}

引用次数: 0