Chemoradiotherapy (CRT) followed by consolidation of immune checkpoint inhibitors (ICIs), such as durvalumab or pembrolizumab, for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression <1% remains a topic of controversy. Previous studies from PubMed, Cochrane Library and Embase databases were searched for a meta-analysis. A total of 16 studies were included in part one of the meta-analysis and it was observed that consolidation of ICIs after CRT improved overall survival (OS) [hazard ratio (HR) 1.46; P=0.005] and progression-free survival (PFS) (HR 1.26; P=0.023) for the patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%. Then, 15 studies were included in part two of the meta-analysis and the results indicated that the pooled 1, 2 and 3-year OS were 77% vs. 83% (P=0.07), 55% vs. 59% (P=0.327) and 38% vs. 51% (P=0.006) for CRT alone compared with CRT followed by consolidation of ICIs, respectively. The pooled 1, 2 and 3-year PFS were 51% vs. 53% (P=0.632), 29% vs. 40% (P=0.015) and 20% vs. 28% (P=0.153) for CRT alone compared with CRT followed by consolidation of ICIs, respectively. The findings of the present study highlighted that the benefits of CRT followed by consolidation of ICIs were higher compared with CRT alone in patients with unresectable, locally advanced NSCLC and PD-L1 expression <1%. Consolidation of ICIs after CRT would provide greater benefits for locally advanced NSCLC patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%.
对于肿瘤PD-L1表达为<1%的不可切除的局部晚期非小细胞肺癌（NSCLC）患者，化放疗（CRT）后使用免疫检查点抑制剂（ICIs）（如durvalumab或pembrolizumab）进行巩固治疗仍存在争议。我们检索了PubMed、Cochrane Library和Embase数据库中的既往研究，并进行了荟萃分析。第一部分荟萃分析共纳入了16项研究，结果显示，与PD-L1表达<1%的患者相比，PD-L1表达≥1%的患者在CRT后巩固ICIs可改善总生存期（OS）[危险比（HR）1.46；P=0.005]和无进展生存期（PFS）（HR 1.26；P=0.023）。随后，15 项研究被纳入荟萃分析的第二部分，结果显示，单独 CRT 与 CRT 后合并 ICIs 相比，1、2 和 3 年 OS 的总和分别为 77% vs. 83% (P=0.07)、55% vs. 59% (P=0.327) 和 38% vs. 51% (P=0.006)。单用CRT与CRT后合并ICIs相比，1年、2年和3年的PFS分别为51% vs. 53% (P=0.632)、29% vs. 40% (P=0.015)和20% vs. 28% (P=0.153)。本研究结果表明，对于无法切除、局部晚期NSCLC且PD-L1表达为<1%的患者，CRT后巩固ICIs的获益高于单纯CRT。与PD-L1表达为<1%的患者相比，PD-L1表达≥1%的局部晚期NSCLC患者在CRT后巩固使用ICIs的获益更大。
{"title":"Efficacy of consolidation of immune checkpoint inhibitor after chemoradiation for unresectable, locally advanced PD‑L1 negative non‑small cell lung cancer: A systematic review and meta‑analysis.","authors":"Sunyin Rao, Li Min, Jie Zhao, Juan Su, Lianhua Ye","doi":"10.3892/ol.2024.14375","DOIUrl":"https://doi.org/10.3892/ol.2024.14375","url":null,"abstract":"Chemoradiotherapy (CRT) followed by consolidation of immune checkpoint inhibitors (ICIs), such as durvalumab or pembrolizumab, for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression <1% remains a topic of controversy. Previous studies from PubMed, Cochrane Library and Embase databases were searched for a meta-analysis. A total of 16 studies were included in part one of the meta-analysis and it was observed that consolidation of ICIs after CRT improved overall survival (OS) [hazard ratio (HR) 1.46; P=0.005] and progression-free survival (PFS) (HR 1.26; P=0.023) for the patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%. Then, 15 studies were included in part two of the meta-analysis and the results indicated that the pooled 1, 2 and 3-year OS were 77% vs. 83% (P=0.07), 55% vs. 59% (P=0.327) and 38% vs. 51% (P=0.006) for CRT alone compared with CRT followed by consolidation of ICIs, respectively. The pooled 1, 2 and 3-year PFS were 51% vs. 53% (P=0.632), 29% vs. 40% (P=0.015) and 20% vs. 28% (P=0.153) for CRT alone compared with CRT followed by consolidation of ICIs, respectively. The findings of the present study highlighted that the benefits of CRT followed by consolidation of ICIs were higher compared with CRT alone in patients with unresectable, locally advanced NSCLC and PD-L1 expression <1%. Consolidation of ICIs after CRT would provide greater benefits for locally advanced NSCLC patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578053","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}
[This corrects the article DOI: 10.3892/ol.2018.8364.].
[This corrects the article DOI: 10.3892/ol.2018.8364.].
{"title":"Erratum: [Corrigendum] miR‑137 suppresses proliferation, migration and invasion of colon cancer cell lines by targeting TCF4.","authors":"Wei-Ping Bi, Min Xia, Xin-Jian Wang","doi":"10.3892/ol.2024.14378","DOIUrl":"https://doi.org/10.3892/ol.2024.14378","url":null,"abstract":"[This corrects the article DOI: 10.3892/ol.2018.8364.].","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"100 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630427","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}
Yeting Qiu, Aijun Qin, Ronghua Zhao, Jun Ding, William Wei-Guo Jia, Manu Singh, Yanal Murad, Qian Tan, Ganessan Kichenadasse
Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×108 PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).
肉瘤源于间质肿瘤，有许多亚型，占所有成人恶性肿瘤的 1%，占儿童恶性肿瘤的 15%。转移性或复发性肉瘤的预后仍然很差。本研究介绍了两例参加实体瘤 I 期剂量递增试验的肉瘤患者，这些患者曾接受过所有标准疗法，但均告失败。这些患者接受了VG161治疗，VG161是一种免疫刺激型单纯疱疹病毒1型溶瘤病毒，含有IL-12、IL-15和IL-15受体α单位有效载荷，以及程序性细胞死亡1（PD-1）/PD-1配体1阻断肽。两个病例的最佳反应都是病情稳定，同时在剂量为2.5×108 PFU/周期时，无进展生存期显著延长（软骨肉瘤为11.8个月，软组织肉瘤为11.9个月）。此外，对外周血和/或肿瘤活检样本进行的细胞因子、淋巴细胞亚群和相关通路分析显示，该疗法还能激活抗癌免疫。这些令人鼓舞的结果表明，VG161 单药疗法有望成为肉瘤的有效治疗方法，值得通过临床试验进一步研究。报道中的两名患者是在澳大利亚进行的 I 期临床试验的一部分，并在澳大利亚新西兰临床试验注册中心进行了注册（注册号 ACTRN12620000244909；注册日期 2020 年 2 月 26 日）。
{"title":"Oncolytic virotherapy stimulates anti‑tumor immune response and demonstrates activity in advanced sarcoma: Report of two cases.","authors":"Yeting Qiu, Aijun Qin, Ronghua Zhao, Jun Ding, William Wei-Guo Jia, Manu Singh, Yanal Murad, Qian Tan, Ganessan Kichenadasse","doi":"10.3892/ol.2024.14377","DOIUrl":"https://doi.org/10.3892/ol.2024.14377","url":null,"abstract":"Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×10<sup>8</sup> PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"2 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627469","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}
Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy. This was changed to daratumumab, bortezomib and dexamethasone when new paraskeletal lesions were identified, resulting in marked tumor shrinkage. After 15 months, an increase in serum monoclonal protein levels, development of a skeletal lesion in the right second rib and extramedullary disease of the right thoracic mediastinal lymph nodes were noted. Treatment with elotuzumab, pomalidomide and dexamethasone (EPd) resulted in expeditious symptomatic improvement and regression of the lesions. Notably, during daratumumab, bortezomib and dexamethasone treatment, lymphocyte counts gradually increased to a level at which elotuzumab was sufficiently effective. EPd might be a promising strategy for the treatment of patients with relapsed extramedullary MM while on daratumumab treatment.
尽管出现了单克隆抗体，但伴有髓外疾病的多发性骨髓瘤（MM）患者的预后仍然很差。本报告描述了一例罕见的达拉曲单抗难治性多发性骨髓瘤病例，该病例成功接受了艾洛珠单抗、泊马度胺和地塞米松治疗。一名66岁的男性患者被诊断为MM，接受了硼替佐米、来那度胺和地塞米松治疗，随后进行了大剂量化疗和自体干细胞移植。此后，患者接受来那度胺和地塞米松作为维持治疗。在发现新的寄生虫病变后，改为达拉单抗、硼替佐米和地塞米松治疗，结果肿瘤明显缩小。15个月后，发现血清单克隆蛋白水平升高，右侧第二根肋骨出现骨骼病变，右胸纵隔淋巴结出现髓外病变。使用艾洛妥珠单抗、泊马度胺和地塞米松（EPd）治疗后，患者症状迅速改善，病变消退。值得注意的是，在达拉单抗、硼替佐米和地塞米松治疗期间，淋巴细胞计数逐渐增加到艾洛妥珠单抗足够有效的水平。对于正在接受达拉土单抗治疗的髓外复发 MM 患者来说，EPd 可能是一种很有前景的治疗策略。
{"title":"Daratumumab‑resistant multiple myeloma with extramedullary disease successfully treated with combination elotuzumab, pomalidomide and dexamethasone: A case report.","authors":"Masataka Sakashita, Naohi Sahara, Jun Aoki, Takashi Matsunaga, Seiichiro Kobayashi, Shinsuke Kitahara, Tomoki Fujii, Nobuhiro Ohno","doi":"10.3892/ol.2024.14381","DOIUrl":"https://doi.org/10.3892/ol.2024.14381","url":null,"abstract":"Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy. This was changed to daratumumab, bortezomib and dexamethasone when new paraskeletal lesions were identified, resulting in marked tumor shrinkage. After 15 months, an increase in serum monoclonal protein levels, development of a skeletal lesion in the right second rib and extramedullary disease of the right thoracic mediastinal lymph nodes were noted. Treatment with elotuzumab, pomalidomide and dexamethasone (EPd) resulted in expeditious symptomatic improvement and regression of the lesions. Notably, during daratumumab, bortezomib and dexamethasone treatment, lymphocyte counts gradually increased to a level at which elotuzumab was sufficiently effective. EPd might be a promising strategy for the treatment of patients with relapsed extramedullary MM while on daratumumab treatment.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"24 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627584","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}
Colon cancer is a common gastrointestinal malignant tumor. In addition to conventional treatment, thoughtful and comprehensive aftercare should be given to patients. The present study aimed to explore the effects of explain-simulate-practice-communication-support (ESPCS) model nursing on the surgical tolerance, gastrointestinal recovery and self-management efficacy of patients with colon cancer. The clinical data of 136 patients with colon cancer diagnosed and treated at the Second Affiliated Hospital of Harbin Medical University (Harbin, China) from June 2020 to April 2022 were retrospectively analyzed and a total of 84 patients met the inclusion criteria. A total of 42 patients who underwent conventional nursing were included in the conventional nursing group and 42 patients who underwent ESPCS model nursing were included in the ESPCS model nursing group. Surgical tolerance, gastrointestinal recovery, self-management efficacy (Cancer Self-Management Efficacy Scale), quality of life (Comprehensive Quality of Life Inventory-74) and nursing satisfaction were analyzed. Slightly higher proportions of excellent and good surgical tolerance were found in the ESPCS model nursing group (97.62%) compared with those in the conventional nursing group (85.71%); however, no significant difference was shown (P>0.05). Compared with the conventional nursing group, the time needed for gastric tube removal, bowel sound recovery, anal exhaust, first defecation, general food intake and the time until getting out of bed was significantly shorter in the ESPS model nursing group (all P<0.05). Before the intervention, no statistically significant difference was found between the indicators in the Cancer Self-Management Efficacy Scale of the two groups (all P>0.05). After the intervention, the ESPCS model nursing group had significantly higher scores for positive attitude, stress relief and self-determination than the conventional nursing group (all P<0.05). Before intervention, there was no statistically significant difference in the indicators of CQOLI-74 between the two groups (P>0.05). After the intervention, the ESPCS model nursing group also had significantly higher scores for social function, psychological function, life state and somatic function compared with the conventional nursing group (all P<0.05). Higher satisfaction of patients was found in the ESPCS mode group (95.24%) compared with that in the conventional nursing group (78.57%) (P<0.05). Overall, ESPCS mode nursing could effectively elevate the surgical tolerance of patients with colon cancer, promote the recovery of gastrointestinal function, increase self-management efficacy, and improve the quality of life and nursing satisfaction, which is certainly worthy of clinical promotion.
{"title":"Effects of ESPCS mode nursing on the surgical tolerance, gastrointestinal tract recovery and self‑management efficacy of patients with colon cancer.","authors":"Rui Yu, Meiling Sun, Shuli Xia, Li Zhang","doi":"10.3892/ol.2024.14380","DOIUrl":"https://doi.org/10.3892/ol.2024.14380","url":null,"abstract":"Colon cancer is a common gastrointestinal malignant tumor. In addition to conventional treatment, thoughtful and comprehensive aftercare should be given to patients. The present study aimed to explore the effects of explain-simulate-practice-communication-support (ESPCS) model nursing on the surgical tolerance, gastrointestinal recovery and self-management efficacy of patients with colon cancer. The clinical data of 136 patients with colon cancer diagnosed and treated at the Second Affiliated Hospital of Harbin Medical University (Harbin, China) from June 2020 to April 2022 were retrospectively analyzed and a total of 84 patients met the inclusion criteria. A total of 42 patients who underwent conventional nursing were included in the conventional nursing group and 42 patients who underwent ESPCS model nursing were included in the ESPCS model nursing group. Surgical tolerance, gastrointestinal recovery, self-management efficacy (Cancer Self-Management Efficacy Scale), quality of life (Comprehensive Quality of Life Inventory-74) and nursing satisfaction were analyzed. Slightly higher proportions of excellent and good surgical tolerance were found in the ESPCS model nursing group (97.62%) compared with those in the conventional nursing group (85.71%); however, no significant difference was shown (P>0.05). Compared with the conventional nursing group, the time needed for gastric tube removal, bowel sound recovery, anal exhaust, first defecation, general food intake and the time until getting out of bed was significantly shorter in the ESPS model nursing group (all P<0.05). Before the intervention, no statistically significant difference was found between the indicators in the Cancer Self-Management Efficacy Scale of the two groups (all P>0.05). After the intervention, the ESPCS model nursing group had significantly higher scores for positive attitude, stress relief and self-determination than the conventional nursing group (all P<0.05). Before intervention, there was no statistically significant difference in the indicators of CQOLI-74 between the two groups (P>0.05). After the intervention, the ESPCS model nursing group also had significantly higher scores for social function, psychological function, life state and somatic function compared with the conventional nursing group (all P<0.05). Higher satisfaction of patients was found in the ESPCS mode group (95.24%) compared with that in the conventional nursing group (78.57%) (P<0.05). Overall, ESPCS mode nursing could effectively elevate the surgical tolerance of patients with colon cancer, promote the recovery of gastrointestinal function, increase self-management efficacy, and improve the quality of life and nursing satisfaction, which is certainly worthy of clinical promotion.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"50 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630448","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}
Connective tissue growth factor (CTGF) is a target gene of the Hippo signaling pathway. Its differential role in the histological types of gastric cancer (GC) remains unknown; therefore, the present study aimed to confirm the clinical significance of CTGF expression in cancer and stromal cells in patients with GC depending on the histological type. The present study enrolled 589 patients with GC. Immunohistochemistry was used to analyze CTGF expression in cancer and stromal cells. CTGF mRNA expression data and the corresponding clinical information of GC samples were collected from The Cancer Genome Atlas (TCGA) database. Subsequently, the associations between CTGF expression and several clinicopathological factors were investigated. In the present study, CTGF expression was mainly observed in the cytoplasm of cancer and stromal cells. CTGF expression in stromal cells was significantly associated with CTGF expression in cancer cells (P<0.001). CTGF positivity in stromal cells was also significantly associated with intestinal type, non-scirrhous type, tumor depth (T1-2), lymph node metastasis (negative), lymphatic invasion (negative) and tumor size (<5 cm). Low CTGF expression in stromal cells was independently associated with worse overall survival (OS). Furthermore, the OS of patients with low CTGF expression in stromal cells, especially in patients with diffuse-type GC, was significantly worse than patients with high CTGF expression (P=0.022). This trend was similar to that revealed by TCGA data analysis. In conclusion, low CTGF expression was associated with a significantly worse OS in patients with diffuse-type GC. These data indicated that CTGF, and its control by the Hippo pathway, may be considered potential treatment targets in diffuse-type GC.
{"title":"Prognostic significance of connective tissue growth factor expression in stromal cells in patients with diffuse‑type gastric cancer.","authors":"Yuichiro Miki, Mami Yoshii, Ryoko Miyauchi, Hiroaki Kasashima, Tatsunari Fukuoka, Tatsuro Tamura, Masatsune Shibutani, Takahiro Toyokawa, Shigeru Lee, Masakazu Yashiro, Kiyoshi Maeda","doi":"10.3892/ol.2024.14374","DOIUrl":"https://doi.org/10.3892/ol.2024.14374","url":null,"abstract":"Connective tissue growth factor (CTGF) is a target gene of the Hippo signaling pathway. Its differential role in the histological types of gastric cancer (GC) remains unknown; therefore, the present study aimed to confirm the clinical significance of CTGF expression in cancer and stromal cells in patients with GC depending on the histological type. The present study enrolled 589 patients with GC. Immunohistochemistry was used to analyze CTGF expression in cancer and stromal cells. CTGF mRNA expression data and the corresponding clinical information of GC samples were collected from The Cancer Genome Atlas (TCGA) database. Subsequently, the associations between CTGF expression and several clinicopathological factors were investigated. In the present study, CTGF expression was mainly observed in the cytoplasm of cancer and stromal cells. CTGF expression in stromal cells was significantly associated with CTGF expression in cancer cells (P<0.001). CTGF positivity in stromal cells was also significantly associated with intestinal type, non-scirrhous type, tumor depth (T1-2), lymph node metastasis (negative), lymphatic invasion (negative) and tumor size (<5 cm). Low CTGF expression in stromal cells was independently associated with worse overall survival (OS). Furthermore, the OS of patients with low CTGF expression in stromal cells, especially in patients with diffuse-type GC, was significantly worse than patients with high CTGF expression (P=0.022). This trend was similar to that revealed by TCGA data analysis. In conclusion, low CTGF expression was associated with a significantly worse OS in patients with diffuse-type GC. These data indicated that CTGF, and its control by the Hippo pathway, may be considered potential treatment targets in diffuse-type GC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"15 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578143","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}
Tae Jeong Oh, Seunghyun Jang, Su Ji Kim, Min A Woo, Ji Woong Son, In Beom Jeong, Min Hyeok Lee, Sungwhan An
Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (Drosophila), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (PCDHGA12) and paired related homeobox 1 (PRRX1)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). PCDHGA12 and PRRX1 methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of PCDHGA12 and PRRX1 are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.
{"title":"Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample.","authors":"Tae Jeong Oh, Seunghyun Jang, Su Ji Kim, Min A Woo, Ji Woong Son, In Beom Jeong, Min Hyeok Lee, Sungwhan An","doi":"10.3892/ol.2024.14379","DOIUrl":"https://doi.org/10.3892/ol.2024.14379","url":null,"abstract":"Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (<i>Drosophila</i>), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (<i>PCDHGA12</i>) and paired related homeobox 1 (<i>PRRX1</i>)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). <i>PCDHGA12</i> and <i>PRRX1</i> methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of <i>PCDHGA12</i> and <i>PRRX1</i> are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627807","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}
Longxun Zhou, Yuqun Shan, Jun Li, Min Li, Zhen Meng, Na Guo
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.
{"title":"Early growth response 1 regulates dual‑specificity protein phosphatase 1 and inhibits cell migration and invasion of tongue squamous cell carcinoma.","authors":"Longxun Zhou, Yuqun Shan, Jun Li, Min Li, Zhen Meng, Na Guo","doi":"10.3892/ol.2024.14373","DOIUrl":"https://doi.org/10.3892/ol.2024.14373","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"71 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617607","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}
Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.
{"title":"A fully validated LC‑MS/MS method for quantifying bevacizumab in plasma samples from patients with NSCLC and its implications in therapeutic drug monitoring.","authors":"Bo Li, Meng Yang, Xiaoxue Wang, Wenqian Chen, Hongkai Lu, Guan Wang, Liang Sun, Xiaoyang Liu, Xianbo Zuo, Pengmei Li, Lihong Liu, Xianglin Zhang","doi":"10.3892/ol.2024.14356","DOIUrl":"https://doi.org/10.3892/ol.2024.14356","url":null,"abstract":"Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"44 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578457","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}
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