The prognosis of advanced lung adenocarcinoma (LUAD) remains unfavorable, with chemotherapy constituting a primary treatment modality. Discerning the efficacy of chemotherapy for advanced LUAD is imperative. Prior investigations have demonstrated the prognostic value of albumin and D-dimer individually for malignancies; however, the predictive capacity of albumin-to-D-dimer ratios (ADR) for advanced LUAD subjected to first-line platinum-based chemotherapy remains unexplored. A cohort of 313 patients with advanced LUAD was retrospectively examined in this study, spanning from January 2017 to January 2021. ADR threshold values were ascertained via receiver operating characteristic analysis, followed by the evaluation of the association between pretreatment ADR and clinicopathological characteristics, disease control rate (DCR), and overall response rate (ORR) pertinent to first-line chemotherapy. Prognostic factors for progression-free survival (PFS) were determined employing Cox univariate and multivariate analyses. Subsequently, survival data were illustrated utilizing the Kaplan-Meier method and scrutinized through the log-rank test across the entire and subgroup populations. ADR demonstrated a superior area under the curve (AUC) value relative to albumin and D-dimer individually and exhibited enhanced prognostic predictive capability compared to albumin-to-fibrinogen ratios (AFR) for advanced LUAD (AUC: 0.805 vs. 0.640, DeLong test: p<0.001). ADR yielded a cut-off value of 16.608. A greater proportion of non-smokers was observed within the high-ADR group (ADR>16.608) compared to the low-ADR group (ADR≤16.608). Patients in the high-ADR group displayed elevated BMI and Na+ levels and reduced neutrophil count, monocyte count, globulin, and alkaline phosphatase (all p<0.05). Notably, the high-ADR group exhibited heightened DCR (96.7% vs. 89.2%, p=0.008) and ORR rates (70.1% vs. 51.0%, p=0.001) relative to the low-ADR group. Multivariate analysis outcomes indicated that high ADR constituted an independent risk factor for PFS (hazard ratio: 0.24, p<0.001). Furthermore, patients in the high-ADR cohort displayed a significantly prolonged median PFS (254 vs. 142 days, p<0.0001) compared to their low-ADR counterparts. In subpopulations exhibiting favorable implications for PFS, as determined by multivariate analysis, high-ADR patients consistently demonstrated extended PFS durations relative to the low-ADR group (all p<0.0001). Collectively, our findings suggest that ADR constitutes a novel and promising prognostic indicator for advanced LUAD patients, surpassing the accuracy of albumin and D-dimer individually and AFR. ADR thus serves as a potent instrument for assessing treatment effects and PFS in advanced LUAD patients undergoing first-line chemotherapy.
{"title":"Albumin-to-D-dimer ratios: A novel prognostic factor for evaluating first-line chemotherapy efficacy in advanced lung adenocarcinoma patients.","authors":"Liqun Zhang, Xing Li, Zhuo Wang, Zhiyan Zhang, Lei Zhang, Zhaoyang Liu, Lisha Zhang, Shuowen Wang, Tatiana Vitalevna Khorobrykh, Mingze He, Jiawen Xiao","doi":"10.4149/neo_2024_230413N205","DOIUrl":"https://doi.org/10.4149/neo_2024_230413N205","url":null,"abstract":"<p><p>The prognosis of advanced lung adenocarcinoma (LUAD) remains unfavorable, with chemotherapy constituting a primary treatment modality. Discerning the efficacy of chemotherapy for advanced LUAD is imperative. Prior investigations have demonstrated the prognostic value of albumin and D-dimer individually for malignancies; however, the predictive capacity of albumin-to-D-dimer ratios (ADR) for advanced LUAD subjected to first-line platinum-based chemotherapy remains unexplored. A cohort of 313 patients with advanced LUAD was retrospectively examined in this study, spanning from January 2017 to January 2021. ADR threshold values were ascertained via receiver operating characteristic analysis, followed by the evaluation of the association between pretreatment ADR and clinicopathological characteristics, disease control rate (DCR), and overall response rate (ORR) pertinent to first-line chemotherapy. Prognostic factors for progression-free survival (PFS) were determined employing Cox univariate and multivariate analyses. Subsequently, survival data were illustrated utilizing the Kaplan-Meier method and scrutinized through the log-rank test across the entire and subgroup populations. ADR demonstrated a superior area under the curve (AUC) value relative to albumin and D-dimer individually and exhibited enhanced prognostic predictive capability compared to albumin-to-fibrinogen ratios (AFR) for advanced LUAD (AUC: 0.805 vs. 0.640, DeLong test: p<0.001). ADR yielded a cut-off value of 16.608. A greater proportion of non-smokers was observed within the high-ADR group (ADR>16.608) compared to the low-ADR group (ADR≤16.608). Patients in the high-ADR group displayed elevated BMI and Na+ levels and reduced neutrophil count, monocyte count, globulin, and alkaline phosphatase (all p<0.05). Notably, the high-ADR group exhibited heightened DCR (96.7% vs. 89.2%, p=0.008) and ORR rates (70.1% vs. 51.0%, p=0.001) relative to the low-ADR group. Multivariate analysis outcomes indicated that high ADR constituted an independent risk factor for PFS (hazard ratio: 0.24, p<0.001). Furthermore, patients in the high-ADR cohort displayed a significantly prolonged median PFS (254 vs. 142 days, p<0.0001) compared to their low-ADR counterparts. In subpopulations exhibiting favorable implications for PFS, as determined by multivariate analysis, high-ADR patients consistently demonstrated extended PFS durations relative to the low-ADR group (all p<0.0001). Collectively, our findings suggest that ADR constitutes a novel and promising prognostic indicator for advanced LUAD patients, surpassing the accuracy of albumin and D-dimer individually and AFR. ADR thus serves as a potent instrument for assessing treatment effects and PFS in advanced LUAD patients undergoing first-line chemotherapy.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 1","pages":"77-87"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this research, polyethylenimine-functionalized gold nanoclusters (PEI-AuNCs) were synthesized for the delivery of plasmid CMTM5 (pCMTM5) to prostate cancer (PCa) cells, with the objective of elucidating the mechanism underlying its anticancer efficacy. The PEI-AuNCs loaded with pCMTM5 (PEI-AuNCs@pCMTM5) tumor-targeting drug delivery system was established. Subsequently, both the obtained PEI-AuNCs and PEI-AuNCs@pCMTM5 underwent characterization through a transmission electron microscope (TEM) and dynamic light scattering (DLS). Employing RT-qPCR, western blot, flow cytometry, immunofluorescence, and co-immunoprecipitation (co-IP) assays, the consequences of CMTM5 overexpression on the expression of EGFR were investigated. Moreover, the influence of PEI-AuNCs@pCMTM5 on PC-3 cells was assessed through CCK-8, wound healing assay, and Transwell experiments. As a result, the PEI-AuNCs and PEI-AuNCs@pCMTM5 were presented as uniformly dispersed spherical with stable particle sizes and positive charges, showcasing favorable dispersion within the solution. In comparison to Lip2000, the PEI-AuNCs demonstrated superior transfection efficiency and lower cellular toxicity. Following the overexpression of CMTM5, the proliferative capacity of PC-3 cells was markedly suppressed, while both migratory and invasive abilities exhibited noteworthy reduction, with the efficacy of PEI-AuNCs@pCMTM5 consistently outperforming that of free pCMTM5. Subsequent mechanistic investigations unveiled that CMTM5 does not directly inhibit the synthesis of EGFR or facilitate its degradation, but rather influences the endocytic process of EGFR. In conclusion, the PEI-AuNCs nano-delivery system exhibits good biocompatibility and efficaciously conveys pCMTM5 to PCa cells. Crucially, pCMTM5 does not directly interact with EGFR, and CMTM5 governs the malignant progression of PC3 cells by promoting EGFR endocytosis.
{"title":"The role of polyethylenimine-functionalized gold nanoclusters carrying plasmid CMTM5 in impeding the malignant progression of prostate cancer cells by promoting EGFR endocytosis.","authors":"Linjin Li, Chengpeng Li, Feilong Miao, Wu Chen, Xianghui Kong, Ruxian Ye, Rui Feng","doi":"10.4149/neo_2024_231018N544","DOIUrl":"10.4149/neo_2024_231018N544","url":null,"abstract":"<p><p>In this research, polyethylenimine-functionalized gold nanoclusters (PEI-AuNCs) were synthesized for the delivery of plasmid CMTM5 (pCMTM5) to prostate cancer (PCa) cells, with the objective of elucidating the mechanism underlying its anticancer efficacy. The PEI-AuNCs loaded with pCMTM5 (PEI-AuNCs@pCMTM5) tumor-targeting drug delivery system was established. Subsequently, both the obtained PEI-AuNCs and PEI-AuNCs@pCMTM5 underwent characterization through a transmission electron microscope (TEM) and dynamic light scattering (DLS). Employing RT-qPCR, western blot, flow cytometry, immunofluorescence, and co-immunoprecipitation (co-IP) assays, the consequences of CMTM5 overexpression on the expression of EGFR were investigated. Moreover, the influence of PEI-AuNCs@pCMTM5 on PC-3 cells was assessed through CCK-8, wound healing assay, and Transwell experiments. As a result, the PEI-AuNCs and PEI-AuNCs@pCMTM5 were presented as uniformly dispersed spherical with stable particle sizes and positive charges, showcasing favorable dispersion within the solution. In comparison to Lip2000, the PEI-AuNCs demonstrated superior transfection efficiency and lower cellular toxicity. Following the overexpression of CMTM5, the proliferative capacity of PC-3 cells was markedly suppressed, while both migratory and invasive abilities exhibited noteworthy reduction, with the efficacy of PEI-AuNCs@pCMTM5 consistently outperforming that of free pCMTM5. Subsequent mechanistic investigations unveiled that CMTM5 does not directly inhibit the synthesis of EGFR or facilitate its degradation, but rather influences the endocytic process of EGFR. In conclusion, the PEI-AuNCs nano-delivery system exhibits good biocompatibility and efficaciously conveys pCMTM5 to PCa cells. Crucially, pCMTM5 does not directly interact with EGFR, and CMTM5 governs the malignant progression of PC3 cells by promoting EGFR endocytosis.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"48-59"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In various malignant tumors (including bladder cancer) poor prognosis is associated with hypoxia and therapeutic resistance. Evidence indicates that in bladder cancer, microRNAs (miRNAs) have vital functions in acquired drug resistance. However, the involvement of miRNAs in hypoxia-mediated bladder cancer doxorubicin (Dox) resistance is unknown. Herein, we showed that hypoxia and Dox treatment downregulated miR-15a-5p expression. Using UM-UC-3 and J82 bladder cancer cell lines and in vivo mouse models of bladder cancer, we confirmed that miR-15a-5p arrests tumor cell growth and Dox resistance in vitro and in vivo. Furthermore, we determined the interaction between miR-15a-5p and eukaryotic translation initiation factor 5A-2 (eIF5A2) using dual luciferase reporters and quantitative real-time reverse transcription polymerase chain reaction assays. We also showed that a miR-15a-5p agomir repressed EIF5A2 expression in bladder cancer cells, thereby inhibiting the epithelial-mesenchymal transition (EMT) induced by Dox or hypoxia. Moreover, ectopic expression of miR-15a-5p abrogated eIF5A2-mediated Dox resistance in bladder cancer cells. Collectively, these data indicated that hypoxia promotes tumor growth and chemoresistance through the HIF-1α/miR-15a-5p/eIFTA2/EMT pathway. This new finding not only has implications for improving our understanding of the Dox resistance process during bladder cancer progression but also indicates that the miR-15a-5p agomir is a promising tool to prevent Dox resistance in patients with bladder cancer.
{"title":"microRNA-15a-5p suppresses hypoxia-induced tumor growth and chemoresistance in bladder cancer by binding to eIF5A2.","authors":"Jinsong Yang, Haoyi Xiang, Mengjing Cheng, Xue Jiang, Ying Chen, Lingyan Zheng, Senxiang Yan, Shufen Zhang, Cheng Zhang, Wei Chen, Dajin Chen","doi":"10.4149/neo_2024_230915N489","DOIUrl":"https://doi.org/10.4149/neo_2024_230915N489","url":null,"abstract":"<p><p>In various malignant tumors (including bladder cancer) poor prognosis is associated with hypoxia and therapeutic resistance. Evidence indicates that in bladder cancer, microRNAs (miRNAs) have vital functions in acquired drug resistance. However, the involvement of miRNAs in hypoxia-mediated bladder cancer doxorubicin (Dox) resistance is unknown. Herein, we showed that hypoxia and Dox treatment downregulated miR-15a-5p expression. Using UM-UC-3 and J82 bladder cancer cell lines and in vivo mouse models of bladder cancer, we confirmed that miR-15a-5p arrests tumor cell growth and Dox resistance in vitro and in vivo. Furthermore, we determined the interaction between miR-15a-5p and eukaryotic translation initiation factor 5A-2 (eIF5A2) using dual luciferase reporters and quantitative real-time reverse transcription polymerase chain reaction assays. We also showed that a miR-15a-5p agomir repressed EIF5A2 expression in bladder cancer cells, thereby inhibiting the epithelial-mesenchymal transition (EMT) induced by Dox or hypoxia. Moreover, ectopic expression of miR-15a-5p abrogated eIF5A2-mediated Dox resistance in bladder cancer cells. Collectively, these data indicated that hypoxia promotes tumor growth and chemoresistance through the HIF-1α/miR-15a-5p/eIFTA2/EMT pathway. This new finding not only has implications for improving our understanding of the Dox resistance process during bladder cancer progression but also indicates that the miR-15a-5p agomir is a promising tool to prevent Dox resistance in patients with bladder cancer.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 1","pages":"60-69"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.4149/neo_2024_230517N262
Wenhao Ji, Youhua Jiang, Yuetong Li, Weimin Mao, Lisong Teng
Neoadjuvant chemoimmunotherapy plays a crucial role in resectable non-small cell lung cancer (NSCLC). Neoadjuvant chemotherapy before sleeve lobectomy was safe and feasible, but the impact of neoadjuvant chemoimmunotherapy before sleeve lobectomy was unclear. In our retrospective study, patients diagnosed as stage IIB to IIIB resectable NSCLC between December 1, 2018 and December 1, 2020 in the Department of Thoracic Surgery, Zhejiang Cancer Hospital were collected. We analyzed the efficacy and safety of neoadjuvant chemoimmunotherapy for resectable NSCLC patients and analyzed the impact of different types of surgery on postoperative complications, surgical difficulty, and long-term survival. In total, 56 patients were included in this retrospective study. With a median follow-up of 35 months, 1-year EFS, 2-year EFS, and 3-year EFS were 87.5%, 80.4%, and 76.7%, respectively. 1-year OS, 2-year OS, and 3-year OS were 96.4%, 91.1%, and 85.6%. respectively. Both median EFS and OS were not reached. The percentage of patients with pCR was 51.8%. 48 (85.7%) patients had nodal downstaging and primary tumor downstaging. In 40 (61.4%) patients occurred neoadjuvant chemoimmunotherapy-related adverse events (AEs), most of them of Grade 1 and 2. Postoperative complications occurred in 19 (33.9%) patients. Subgroup analysis showed that sleeve lobectomy was related to better survival and had no impact on operation duration, hospital stay, intraoperative blood loss, and postoperative complications. Neoadjuvant chemoimmunotherapy led to a high pCR rate, favorable 3-year survival rate, and acceptable AEs. Sleeve lobectomy was safe and related to better survival.
{"title":"Three years follow-up of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer.","authors":"Wenhao Ji, Youhua Jiang, Yuetong Li, Weimin Mao, Lisong Teng","doi":"10.4149/neo_2024_230517N262","DOIUrl":"https://doi.org/10.4149/neo_2024_230517N262","url":null,"abstract":"<p><p>Neoadjuvant chemoimmunotherapy plays a crucial role in resectable non-small cell lung cancer (NSCLC). Neoadjuvant chemotherapy before sleeve lobectomy was safe and feasible, but the impact of neoadjuvant chemoimmunotherapy before sleeve lobectomy was unclear. In our retrospective study, patients diagnosed as stage IIB to IIIB resectable NSCLC between December 1, 2018 and December 1, 2020 in the Department of Thoracic Surgery, Zhejiang Cancer Hospital were collected. We analyzed the efficacy and safety of neoadjuvant chemoimmunotherapy for resectable NSCLC patients and analyzed the impact of different types of surgery on postoperative complications, surgical difficulty, and long-term survival. In total, 56 patients were included in this retrospective study. With a median follow-up of 35 months, 1-year EFS, 2-year EFS, and 3-year EFS were 87.5%, 80.4%, and 76.7%, respectively. 1-year OS, 2-year OS, and 3-year OS were 96.4%, 91.1%, and 85.6%. respectively. Both median EFS and OS were not reached. The percentage of patients with pCR was 51.8%. 48 (85.7%) patients had nodal downstaging and primary tumor downstaging. In 40 (61.4%) patients occurred neoadjuvant chemoimmunotherapy-related adverse events (AEs), most of them of Grade 1 and 2. Postoperative complications occurred in 19 (33.9%) patients. Subgroup analysis showed that sleeve lobectomy was related to better survival and had no impact on operation duration, hospital stay, intraoperative blood loss, and postoperative complications. Neoadjuvant chemoimmunotherapy led to a high pCR rate, favorable 3-year survival rate, and acceptable AEs. Sleeve lobectomy was safe and related to better survival.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 1","pages":"88-97"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Semaphorins are originally described as regulators of nervous system development. Besides, members of the semaphorin family play important roles in the growth, metastasis, and angiogenesis of solid tumors. In contrast to the other semaphorin subclasses, semaphorin class 4 has both membrane-bound and active soluble forms. Soluble class 4 semaphorins in body fluids (blood and saliva) may serve as potential biomarkers for early diagnosis and prognosis prediction of specific cancers. The class 4 semaphorins also transduce signal in cancer cells in a cell membrane-bound form, thereby regulating cancer progression. In solid tumors, class 4 semaphorins can act as ligands in active soluble forms, regulating cancer progression via autocrine and paracrine to activate signal transduction in cancer cells or endothelial cells in the tumor microenvironment. Targeting class 4 semaphorins may be a novel strategy for specific cancer therapy. However, the expression of class 4 semaphorins in solid tumors and the responsive pathogenesis are still controversial. Therefore, this review summarizes the specific expression regulation of class 4 semaphorin members in different types of solid tumors and the mechanisms involved in cancer progression.
{"title":"Expression patterns and pathogenesis of Semaphorin class 4 subfamily proteins in solid tumors.","authors":"Dongjun Jiang, Xiaoli Chen, Xiuting Li, Jian Qiu, Peng Xu, Xuezhi Li","doi":"10.4149/neo_2024_230907N475","DOIUrl":"10.4149/neo_2024_230907N475","url":null,"abstract":"<p><p>Semaphorins are originally described as regulators of nervous system development. Besides, members of the semaphorin family play important roles in the growth, metastasis, and angiogenesis of solid tumors. In contrast to the other semaphorin subclasses, semaphorin class 4 has both membrane-bound and active soluble forms. Soluble class 4 semaphorins in body fluids (blood and saliva) may serve as potential biomarkers for early diagnosis and prognosis prediction of specific cancers. The class 4 semaphorins also transduce signal in cancer cells in a cell membrane-bound form, thereby regulating cancer progression. In solid tumors, class 4 semaphorins can act as ligands in active soluble forms, regulating cancer progression via autocrine and paracrine to activate signal transduction in cancer cells or endothelial cells in the tumor microenvironment. Targeting class 4 semaphorins may be a novel strategy for specific cancer therapy. However, the expression of class 4 semaphorins in solid tumors and the responsive pathogenesis are still controversial. Therefore, this review summarizes the specific expression regulation of class 4 semaphorin members in different types of solid tumors and the mechanisms involved in cancer progression.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"1-12"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.
{"title":"The impact of neo/adjuvant treatment choices on prognosis for surgically treated small-cell neuroendocrine carcinoma of the cervix.","authors":"Deying Zhao, Shaoxing Sun, Zhiyong Yang, Ping Wang, Hui Qiu","doi":"10.4149/neo_2023_230802N404","DOIUrl":"10.4149/neo_2023_230802N404","url":null,"abstract":"<p><p>Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"70-76"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.4149/neo_2023_230721N380
Blanka Rosova, Jan Proks, Alzbeta Filipova, Dimitar Hadzi Nikolov, Renata Chloupkova, Igor Richter, Arpad Szabo, Aneta Rozsypalova, Radoslav Matej, Bohuslav Melichar, Tomas Buchler, Josef Dvorak
The aim of this study was to investigate the prognostic significance of membranous β-catenin and cytoplasmic β-catenin expression in pancreatic cancer patients (pts). One hundred pts with histologically verified exocrine pancreatic ductal adenocarcinoma were retrospectively studied. The membranous β-catenin, cytoplasmic β-catenin, and cell nucleus β-catenin expression were immunohistochemically evaluated. The expression of membranous β-catenin was <5% in none of the pts, 5-25% in one patient, 26-50% in 2 pts, 51-75% in 14 pts, and >75% in 81 pts. The expression of cytoplasmic β-catenin was <5% in 34 pts, 5-25% in 42 pts, 26-50% in 18 pts, 51-75% in 3 pts, and >75% in one patient. The expression of β-catenin in the cell nucleus was negative in all pts. At the time of the last follow-up, 21 pts were alive and 79 pts had died. Median OS was 1.3 (0.4-2.3) years in pts with membranous β-catenin expression ≤75% and 1.7 (1.3-2.1) years in pts with membranous β-catenin expression >75% (p=0.045). Median OS was (1.3-2.0) 1.6 years in pts with cytoplasmic β-catenin expression ≤25% and 0.9 (0.5-1.2) years in pts with cytoplasmic β-catenin expression >25% (p=0.040). In the univariate Cox proportional hazard models HR (95% CI) was 0.556 (0.311-0.995) in pts with membranous β-catenin expression >75% (p=0.048) and 2.200 (1.216-3.980) in pts with cytoplasmic β-catenin expression >25% (p=0.009). The present results indicate a favorable prognostic significance of membranous β-catenin expression in pancreatic cancer.
{"title":"Favorable prognostic significance of membranous β-catenin expression and negative prognostic significance of cytoplasmic β-catenin expression in pancreatic cancer.","authors":"Blanka Rosova, Jan Proks, Alzbeta Filipova, Dimitar Hadzi Nikolov, Renata Chloupkova, Igor Richter, Arpad Szabo, Aneta Rozsypalova, Radoslav Matej, Bohuslav Melichar, Tomas Buchler, Josef Dvorak","doi":"10.4149/neo_2023_230721N380","DOIUrl":"10.4149/neo_2023_230721N380","url":null,"abstract":"<p><p>The aim of this study was to investigate the prognostic significance of membranous β-catenin and cytoplasmic β-catenin expression in pancreatic cancer patients (pts). One hundred pts with histologically verified exocrine pancreatic ductal adenocarcinoma were retrospectively studied. The membranous β-catenin, cytoplasmic β-catenin, and cell nucleus β-catenin expression were immunohistochemically evaluated. The expression of membranous β-catenin was <5% in none of the pts, 5-25% in one patient, 26-50% in 2 pts, 51-75% in 14 pts, and >75% in 81 pts. The expression of cytoplasmic β-catenin was <5% in 34 pts, 5-25% in 42 pts, 26-50% in 18 pts, 51-75% in 3 pts, and >75% in one patient. The expression of β-catenin in the cell nucleus was negative in all pts. At the time of the last follow-up, 21 pts were alive and 79 pts had died. Median OS was 1.3 (0.4-2.3) years in pts with membranous β-catenin expression ≤75% and 1.7 (1.3-2.1) years in pts with membranous β-catenin expression >75% (p=0.045). Median OS was (1.3-2.0) 1.6 years in pts with cytoplasmic β-catenin expression ≤25% and 0.9 (0.5-1.2) years in pts with cytoplasmic β-catenin expression >25% (p=0.040). In the univariate Cox proportional hazard models HR (95% CI) was 0.556 (0.311-0.995) in pts with membranous β-catenin expression >75% (p=0.048) and 2.200 (1.216-3.980) in pts with cytoplasmic β-catenin expression >25% (p=0.009). The present results indicate a favorable prognostic significance of membranous β-catenin expression in pancreatic cancer.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 6","pages":"796-803"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We assessed the efficacy and safety of sintilimab [an anti-programmed death (PD-1)] plus bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC). The patients received sintilimab (200 mg) plus IBI305 (7.5 mg/kg) and HAIC (FOLFOX for 23 h) and were treated every 3 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC) per mRECIST v1.1. Twenty-nine patients were enrolled in our clinical trial (1 patient voluntarily withdrew due to adverse events after the initial treatment). Objective response was reached in 17/29 (58.6%) patients per mRECIST. A total of 19/29 (65.5%) patients became eligible for further treatment; 14 of them completed surgical resection; 1 (5.3%) achieved pathological complete response (pCR); and 5 (26.3%) reached major partial response (mPR). The 1-year OS rate was better in the PR or pCR+mPR+PR group than in the PD+SD group by either mRECIST or pathological assessment (p=0.039 and 0.006). The 1-year EFS rate was better in the PR group than in the PD+SD group by pathological assessment (p=0.007). The most common treatment-related adverse events (TEAEs) in 30 HCC patients included thrombocytopenia (40.0%), hypertension (23.3%), and leukopenia (23.3%). The grade 3-5 TEAEs that were observed were hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients.
{"title":"Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial.","authors":"Dongming Liu, Han Mu, Changfu Liu, Weihao Zhang, Yunlong Cui, Qiang Wu, Xiaolin Zhu, Feng Fang, Wei Zhang, Wenge Xing, Qiang Li, Tianqiang Song, Wei Lu, Huikai Li","doi":"10.4149/neo_2023_230806N413","DOIUrl":"10.4149/neo_2023_230806N413","url":null,"abstract":"<p><p>We assessed the efficacy and safety of sintilimab [an anti-programmed death (PD-1)] plus bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC). The patients received sintilimab (200 mg) plus IBI305 (7.5 mg/kg) and HAIC (FOLFOX for 23 h) and were treated every 3 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC) per mRECIST v1.1. Twenty-nine patients were enrolled in our clinical trial (1 patient voluntarily withdrew due to adverse events after the initial treatment). Objective response was reached in 17/29 (58.6%) patients per mRECIST. A total of 19/29 (65.5%) patients became eligible for further treatment; 14 of them completed surgical resection; 1 (5.3%) achieved pathological complete response (pCR); and 5 (26.3%) reached major partial response (mPR). The 1-year OS rate was better in the PR or pCR+mPR+PR group than in the PD+SD group by either mRECIST or pathological assessment (p=0.039 and 0.006). The 1-year EFS rate was better in the PR group than in the PD+SD group by pathological assessment (p=0.007). The most common treatment-related adverse events (TEAEs) in 30 HCC patients included thrombocytopenia (40.0%), hypertension (23.3%), and leukopenia (23.3%). The grade 3-5 TEAEs that were observed were hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 6","pages":"811-818"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.4149/neo_2023_230103N4
Xinlin Yang, Miao Zhang, Wei Xia, Zhongchao Mai, Ying Ye, Bin Zhao, Yanan Song
ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) is involved in intracellular glutathione depletion, ferroptosis, and tumorigenesis. The functional role of CHAC1 expression in thyroid carcinoma has not yet been established. The present study aimed to investigate the impact and mechanisms of CHAC1 on ferroptosis and radiation sensitivity in thyroid carcinoma. CHAC1 expression was examined in tumor tissue specimens and microarrays and thyroid carcinoma cell lines. CHAC1 was silenced or overexpressed by lentivirus transfection in thyroid carcinoma cells. Cell viability and lipid ROS levels were evaluated by Cell Counting Kit-8 and flow cytometry, respectively. The effect of CHAC1 on tumor growth in vivo was also measured. Ferroptosis-related proteins were measured by western blotting. CHAC1 expression was decreased in patients with thyroid carcinoma, and overexpression of CHAC1 suppressed cell viability of BCPAP cells and tumor growth in xenografted nude mice. Exposure to Ferrostatin-1, a ferroptosis inhibitor, significantly attenuated the inhibitory effects of CHAC1 overexpression on cell viability. In CHAC1-overexpressing BCPAP cells, ferroptosis was induced as indicated by increased lipid ROS production and PTGS2 expression. Knocking down of CHAC1 in K1 cells significantly induced cell viability, reduced lipid ROS production and PTGS2 expression, and enhanced GPX4 expression. Such effects were attenuated by RSL3, a ferroptosis inducer. Furthermore, we showed that CHAC1 overexpression enhanced radiation sensitivity in BCPAP cells as indicated by decreased cell viability, while CHAC1 knockdown had reversed effects in K1 cells as indicated by increased cell viability. Taken together, CHAC1 overexpression promoted ferroptosis and enhanced radiation sensitivity in thyroid carcinoma.
{"title":"CHAC1 promotes cell ferroptosis and enhances radiation sensitivity in thyroid carcinoma.","authors":"Xinlin Yang, Miao Zhang, Wei Xia, Zhongchao Mai, Ying Ye, Bin Zhao, Yanan Song","doi":"10.4149/neo_2023_230103N4","DOIUrl":"10.4149/neo_2023_230103N4","url":null,"abstract":"<p><p>ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) is involved in intracellular glutathione depletion, ferroptosis, and tumorigenesis. The functional role of CHAC1 expression in thyroid carcinoma has not yet been established. The present study aimed to investigate the impact and mechanisms of CHAC1 on ferroptosis and radiation sensitivity in thyroid carcinoma. CHAC1 expression was examined in tumor tissue specimens and microarrays and thyroid carcinoma cell lines. CHAC1 was silenced or overexpressed by lentivirus transfection in thyroid carcinoma cells. Cell viability and lipid ROS levels were evaluated by Cell Counting Kit-8 and flow cytometry, respectively. The effect of CHAC1 on tumor growth in vivo was also measured. Ferroptosis-related proteins were measured by western blotting. CHAC1 expression was decreased in patients with thyroid carcinoma, and overexpression of CHAC1 suppressed cell viability of BCPAP cells and tumor growth in xenografted nude mice. Exposure to Ferrostatin-1, a ferroptosis inhibitor, significantly attenuated the inhibitory effects of CHAC1 overexpression on cell viability. In CHAC1-overexpressing BCPAP cells, ferroptosis was induced as indicated by increased lipid ROS production and PTGS2 expression. Knocking down of CHAC1 in K1 cells significantly induced cell viability, reduced lipid ROS production and PTGS2 expression, and enhanced GPX4 expression. Such effects were attenuated by RSL3, a ferroptosis inducer. Furthermore, we showed that CHAC1 overexpression enhanced radiation sensitivity in BCPAP cells as indicated by decreased cell viability, while CHAC1 knockdown had reversed effects in K1 cells as indicated by increased cell viability. Taken together, CHAC1 overexpression promoted ferroptosis and enhanced radiation sensitivity in thyroid carcinoma.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 6","pages":"777-786"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaccines composed of autophagosomes derived from tumor cells called DRibbles (DRiPs-containing blebs) are involved in the cross-presentation of tumor antigens, thus inducing cross-reactive T-cell responses against the tumor. Compared with traditional tumor lysate vaccines, autophagosome vaccines were found to be better sources of multiple tumor-associated antigens (TAAs) that activate antigen-specific T-cells. However, the involvement of tumor neoantigens in the immune responses of autophagosome vaccines remains unclear. The present study showed that exogenous autophagosome vaccines (DRibbles) combined with immune adjuvants (anti-OX40 antibody and ATP) can effectively activate functional T cells in vitro. Importantly, the combination of exogenous tumor-derived autophagosome vaccines and immune adjuvants was found to induce tumor regression in B16F10 and 4T1 tumor-bearing mice. The combination of autophagosome-enriched DRibbles with anti-OX40 antibody and ATP also exhibited optimal immune stimulation and antitumor efficiency in vivo. The effectiveness of exogenous DRibble vaccines was mainly due to their enhancement of tumor immunogenicity by increasing the presentation and release of tumor neoantigens. These findings suggest that this immunotherapeutic method may be effective in the treatment of cancer.
{"title":"Tumor-derived autophagosome vaccines combined with immune adjuvants mediate antitumor immune responses via the neoantigen pathway.","authors":"Jia Yuan, Yue Chang, Yalan Dai, Yutong Chen, Rongbin Yue, Linjuan Zeng","doi":"10.4149/neo_2023_230125N41","DOIUrl":"10.4149/neo_2023_230125N41","url":null,"abstract":"<p><p>Vaccines composed of autophagosomes derived from tumor cells called DRibbles (DRiPs-containing blebs) are involved in the cross-presentation of tumor antigens, thus inducing cross-reactive T-cell responses against the tumor. Compared with traditional tumor lysate vaccines, autophagosome vaccines were found to be better sources of multiple tumor-associated antigens (TAAs) that activate antigen-specific T-cells. However, the involvement of tumor neoantigens in the immune responses of autophagosome vaccines remains unclear. The present study showed that exogenous autophagosome vaccines (DRibbles) combined with immune adjuvants (anti-OX40 antibody and ATP) can effectively activate functional T cells in vitro. Importantly, the combination of exogenous tumor-derived autophagosome vaccines and immune adjuvants was found to induce tumor regression in B16F10 and 4T1 tumor-bearing mice. The combination of autophagosome-enriched DRibbles with anti-OX40 antibody and ATP also exhibited optimal immune stimulation and antitumor efficiency in vivo. The effectiveness of exogenous DRibble vaccines was mainly due to their enhancement of tumor immunogenicity by increasing the presentation and release of tumor neoantigens. These findings suggest that this immunotherapeutic method may be effective in the treatment of cancer.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"747-760"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}