Pub Date : 2024-09-01DOI: 10.21873/anticanres.17198
Toru Aoyama, Yukio Maezawa, Itaru Hashimoto
Gastric cancer (GC) is the fifth most common cancer and fourth leading cause of cancer-related deaths worldwide. Gastrectomy with lymphadenectomy is the standard treatment for both early and locally advanced GC. Laparoscopic surgery has been widely used for decades for the treatment of benign diseases, such as cholecystectomy and appendectomy. The use of laparoscopy-assisted distal gastrectomy (LADG) for the treatment of gastric cancer was first described by Kitano in 1994. Since then, the number of gastric cancer cases treated with LADG has gradually increased. Recently, robot-assisted gastrectomy (RDG) has also been introduced in the treatment of GC. To date, several randomized control trials (RCT) have been conducted to evaluate the safety, feasibility, and efficacy of LADG and RDG in comparison to open distal gastrectomy (ODG). However, the short- and long-term oncological outcomes of LADG and RDG remain controversial and have not been fully evaluated. To optimize GC treatment, especially gastrectomy with lymphadenectomy, it is necessary to understand the characteristics of each approach before gastric cancer treatment. This review summarizes the background, current status, and future perspectives of LADG and RDG in GC treatment using RCT data.
{"title":"Open, Laparoscopy-assisted, Robotic-assisted Distal Gastrectomy for Gastric Cancer: Evidence from Randomized Clinical Trials.","authors":"Toru Aoyama, Yukio Maezawa, Itaru Hashimoto","doi":"10.21873/anticanres.17198","DOIUrl":"https://doi.org/10.21873/anticanres.17198","url":null,"abstract":"<p><p>Gastric cancer (GC) is the fifth most common cancer and fourth leading cause of cancer-related deaths worldwide. Gastrectomy with lymphadenectomy is the standard treatment for both early and locally advanced GC. Laparoscopic surgery has been widely used for decades for the treatment of benign diseases, such as cholecystectomy and appendectomy. The use of laparoscopy-assisted distal gastrectomy (LADG) for the treatment of gastric cancer was first described by Kitano in 1994. Since then, the number of gastric cancer cases treated with LADG has gradually increased. Recently, robot-assisted gastrectomy (RDG) has also been introduced in the treatment of GC. To date, several randomized control trials (RCT) have been conducted to evaluate the safety, feasibility, and efficacy of LADG and RDG in comparison to open distal gastrectomy (ODG). However, the short- and long-term oncological outcomes of LADG and RDG remain controversial and have not been fully evaluated. To optimize GC treatment, especially gastrectomy with lymphadenectomy, it is necessary to understand the characteristics of each approach before gastric cancer treatment. This review summarizes the background, current status, and future perspectives of LADG and RDG in GC treatment using RCT data.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091646","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 : 2024-09-01DOI: 10.21873/anticanres.17199
Weijie Ma, Zhongze Li, Jiexi Wen, Shaofeng Yan
Background/aim: Over-expression of glucose transporters (GLUTs), membrane proteins that facilitate glucose transport, has been implicated in cutaneous melanomas. Our prior studies have demonstrated increased expression of GLUT1 and GLUT3 in melanomas and their association with poorer prognosis. This study aimed to investigate the expression of GLUT isoforms 4 and 8 in melanocytic lesions, examine the co-expression status of multiple GLUTs, and evaluate their prognostic significance.
Materials and methods: We analyzed 171 melanocytic lesions (97 primary melanomas, 19 metastatic melanomas, and 55 nevi) using a tissue microarray and immunohistochemistry using antibodies against GLUT4 and GLUT8. Membranous expression of GLUTs was scored using a semi-quantitative method. A combined GLUT total score was generated by summing scores from GLUT1, GLUT3, GLUT4, and GLUT8 (including data from previous studies).
Results: A significant up-regulation of GLUT4 and GLUT8 expression was found in melanomas compared to nevi (p<0.0001 for both). Concurrent over-expression of multiple GLUTs was more prevalent in melanomas compared to nevi (p<0.0001), and it was also more frequent in metastatic melanomas compared to primary melanomas (p=0.047). Importantly, high total GLUT expression scores were significantly correlated with negative prognostic factors, such as ulceration and mitoses (p=0.03 and p=0.008 respectively). Additionally, Kaplan-Meier survival curves revealed that patients with elevated GLUT total score in their melanomas had a lower disease-specific survival (p=0.006). Furthermore, analysis of multiple GLUTs improved diagnostic sensitivity.
Conclusion: Similar to GLUT1 and GLUT3, melanoma exhibits up-regulation of GLUT 4 and GLUT8 compared to nevi. Evaluation of multiple GLUT isoforms improves diagnostic and prognostic values.
{"title":"The Expression and Prognostic Value of Multiple Glucose Transporters in Cutaneous Melanoma.","authors":"Weijie Ma, Zhongze Li, Jiexi Wen, Shaofeng Yan","doi":"10.21873/anticanres.17199","DOIUrl":"https://doi.org/10.21873/anticanres.17199","url":null,"abstract":"<p><strong>Background/aim: </strong>Over-expression of glucose transporters (GLUTs), membrane proteins that facilitate glucose transport, has been implicated in cutaneous melanomas. Our prior studies have demonstrated increased expression of GLUT1 and GLUT3 in melanomas and their association with poorer prognosis. This study aimed to investigate the expression of GLUT isoforms 4 and 8 in melanocytic lesions, examine the co-expression status of multiple GLUTs, and evaluate their prognostic significance.</p><p><strong>Materials and methods: </strong>We analyzed 171 melanocytic lesions (97 primary melanomas, 19 metastatic melanomas, and 55 nevi) using a tissue microarray and immunohistochemistry using antibodies against GLUT4 and GLUT8. Membranous expression of GLUTs was scored using a semi-quantitative method. A combined GLUT total score was generated by summing scores from GLUT1, GLUT3, GLUT4, and GLUT8 (including data from previous studies).</p><p><strong>Results: </strong>A significant up-regulation of GLUT4 and GLUT8 expression was found in melanomas compared to nevi (p<0.0001 for both). Concurrent over-expression of multiple GLUTs was more prevalent in melanomas compared to nevi (p<0.0001), and it was also more frequent in metastatic melanomas compared to primary melanomas (p=0.047). Importantly, high total GLUT expression scores were significantly correlated with negative prognostic factors, such as ulceration and mitoses (p=0.03 and p=0.008 respectively). Additionally, Kaplan-Meier survival curves revealed that patients with elevated GLUT total score in their melanomas had a lower disease-specific survival (p=0.006). Furthermore, analysis of multiple GLUTs improved diagnostic sensitivity.</p><p><strong>Conclusion: </strong>Similar to GLUT1 and GLUT3, melanoma exhibits up-regulation of GLUT 4 and GLUT8 compared to nevi. Evaluation of multiple GLUT isoforms improves diagnostic and prognostic values.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091698","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}
Background/aim: Various biomarkers are utilized in the field of breast cancer. Human lymphocyte antigen (HLA) class I molecules have a critical role in cancer immune surveillance. Therefore, this study aimed to assess the HLA class I expression and analyze the correlation with clinicopathologic factors in breast cancer.
Patients and methods: We investigated the clinical pathology archives of 150 consecutive patients with breast cancer who underwent a curative operation at the Sapporo Medical University, Japan, from January 2012 to December 2014. Immunohistochemical staining was used to evaluate HLA class I expression and CD8-positive T cell infiltration. The Pearson χ2 test was used to assess HLA class I expression level and clinicopathological parameters. The Kaplan-Meier method was used to evaluate survival and the log-rank test to analyze the differences between survival curves.
Results: Patients with dull/negative HLA class I had significantly poor disease-free survival (DFS) compared with those with positive HLA class I (p=0.0073). Univariate analyses revealed that pT, pN, positive lymphatic invasion, and dull/negative HLA class I were significantly associated with DFS. Multivariate analyses revealed dull/negative HLA class I as an independent poor prognostic factor (hazard ratio=2.75, 95% confidence interval=1.30-5.80, p=0.008).
Conclusion: HLA class I expression level may have a very sensitive prognostic effect on patients with breast cancer.
背景/目的:乳腺癌领域使用了多种生物标记物。人类淋巴细胞抗原(HLA)I类分子在癌症免疫监视中起着至关重要的作用。因此,本研究旨在评估 HLA I 类分子的表达,并分析其与乳腺癌临床病理因素的相关性:我们调查了 2012 年 1 月至 2014 年 12 月期间在日本札幌医科大学接受治愈性手术的 150 名连续乳腺癌患者的临床病理档案。免疫组化染色用于评估 HLA I 类表达和 CD8 阳性 T 细胞浸润。皮尔逊χ2检验用于评估HLA I类表达水平和临床病理参数。采用Kaplan-Meier法评估生存率,并用log-rank检验分析生存曲线之间的差异:结果:与HLA I级阳性患者相比,HLA I级阴性患者的无病生存率(DFS)明显较低(P=0.0073)。单变量分析显示,pT、pN、淋巴侵袭阳性和HLA I级阴性与无病生存期显著相关。多变量分析显示,HLA I级阴性/迟钝是一个独立的不良预后因素(危险比=2.75,95%置信区间=1.30-5.80,P=0.008):结论:HLA I类表达水平可能对乳腺癌患者的预后有非常敏感的影响。
{"title":"Prognostic Impact of Human Lymphocyte Antigen (HLA) Class I Expression in Patients With Breast Cancer.","authors":"Motonobu Uchiyama, Hiroaki Shima, Goro Kutomi, Daisuke Kyuno, Asaka Wada, Yoko Kuga, Yasuaki Tamura, Yoshihiko Hirohashi, Toshihiko Torigoe, Ichiro Takemasa","doi":"10.21873/anticanres.17233","DOIUrl":"https://doi.org/10.21873/anticanres.17233","url":null,"abstract":"<p><strong>Background/aim: </strong>Various biomarkers are utilized in the field of breast cancer. Human lymphocyte antigen (HLA) class I molecules have a critical role in cancer immune surveillance. Therefore, this study aimed to assess the HLA class I expression and analyze the correlation with clinicopathologic factors in breast cancer.</p><p><strong>Patients and methods: </strong>We investigated the clinical pathology archives of 150 consecutive patients with breast cancer who underwent a curative operation at the Sapporo Medical University, Japan, from January 2012 to December 2014. Immunohistochemical staining was used to evaluate HLA class I expression and CD8-positive T cell infiltration. The Pearson χ<sup>2</sup> test was used to assess HLA class I expression level and clinicopathological parameters. The Kaplan-Meier method was used to evaluate survival and the log-rank test to analyze the differences between survival curves.</p><p><strong>Results: </strong>Patients with dull/negative HLA class I had significantly poor disease-free survival (DFS) compared with those with positive HLA class I (p=0.0073). Univariate analyses revealed that pT, pN, positive lymphatic invasion, and dull/negative HLA class I were significantly associated with DFS. Multivariate analyses revealed dull/negative HLA class I as an independent poor prognostic factor (hazard ratio=2.75, 95% confidence interval=1.30-5.80, p=0.008).</p><p><strong>Conclusion: </strong>HLA class I expression level may have a very sensitive prognostic effect on patients with breast cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091668","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}
Background/aim: The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear.
Patients and methods: In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m2) and low- (<25 kg/m2) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated.
Results: Patients with a high BMI had lower skeletal mass index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) compared to those in the low-BMI cohort. The baseline Child-Pugh scores and Barcelona Clinic Liver Cancer stages were comparable between the two cohorts. The overall survival (OS) was better in the high BMI group compared to the low BMI group (median, 913 vs. 484 days; p=0.008). SMI had a strong influence on OS. Additionally, low BMI, VATI, SATI, and visceral-to-subcutaneous fat ratio (VSR) in the LEN treatment group were associated with shorter progression-free survival (PFS).
Conclusion: Following systemic treatment for uHCC, patients with low BMI have a poor prognosis. Among anthropometric factors, low SMI is associated with poor OS. In the LEN treatment group, low VATI may impact PFS negatively.
{"title":"Impact of BMI and Body Composition on First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma.","authors":"Takafumi Yamamoto, Takanori Ito, Kazuyuki Mizuno, Shinya Yokoyama, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Hiroki Kawashima","doi":"10.21873/anticanres.17239","DOIUrl":"https://doi.org/10.21873/anticanres.17239","url":null,"abstract":"<p><strong>Background/aim: </strong>The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear.</p><p><strong>Patients and methods: </strong>In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m<sup>2</sup>) and low- (<25 kg/m<sup>2</sup>) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated.</p><p><strong>Results: </strong>Patients with a high BMI had lower skeletal mass index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) compared to those in the low-BMI cohort. The baseline Child-Pugh scores and Barcelona Clinic Liver Cancer stages were comparable between the two cohorts. The overall survival (OS) was better in the high BMI group compared to the low BMI group (median, 913 vs. 484 days; p=0.008). SMI had a strong influence on OS. Additionally, low BMI, VATI, SATI, and visceral-to-subcutaneous fat ratio (VSR) in the LEN treatment group were associated with shorter progression-free survival (PFS).</p><p><strong>Conclusion: </strong>Following systemic treatment for uHCC, patients with low BMI have a poor prognosis. Among anthropometric factors, low SMI is associated with poor OS. In the LEN treatment group, low VATI may impact PFS negatively.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091638","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}
Background/aim: Radiotherapy-induced malfunction of pacemakers and cardiac defibrillators has been reported, and corresponding guidelines have been developed in various countries. Although several studies have reported the effects of radiotherapy in patients with implantable left ventricular assist device (LVAD), its safety remains unclear. Herein, we report three cases of stereotactic ablative radiotherapy (SABR) using CyberKnife for early-stage lung cancer in patients with implantable LVAD.
Case report: Three patients in their 50s or 60s, including two women and one man, who had LVADs due to dilated or ischemic cardiomyopathy and performance status of 0 or 1, were diagnosed with stage IA2 lung cancer (cT1bN0M0) by imaging only. All three patients were deemed inoperable due to cardiac comorbidity and underwent SABR at the Osaka University Hospital. The total radiation dose was 42-52 Gy, administered in four fractions. All treatment plans were designed to keep the LVAD dose below 2 Gy. In all patients, SABR was completed without acute adverse events or LVAD malfunction. During the follow-up period of 3-29 months, no disease progression or chronic adverse events were observed in any of the patients.
Conclusion: This case series indicated that SABR using CyberKnife is a safe treatment option for early-stage lung cancer in patients with LVAD by reducing the dose to the LVAD.
{"title":"Stereotactic Ablative Radiotherapy for Early-stage Lung Cancer in Patients With Left Ventricular Assist Device: A Case Series.","authors":"Kazuhiko Hayashi, Hiroshi Ishikawa, Kei Fujiwara, Masataka Nakai, Hitoshi Ono, Yasutoshi Fumimoto, Nobuyuki Tamaki, Shotaro Tatekawa, Takero Hirata, Toru Kimura, Haruhiko Hirata, Keisuke Tamari, Yoshito Takeda, Shinichi Shimizu, Yasushi Shintani, Kazuhiko Ogawa","doi":"10.21873/anticanres.17240","DOIUrl":"https://doi.org/10.21873/anticanres.17240","url":null,"abstract":"<p><strong>Background/aim: </strong>Radiotherapy-induced malfunction of pacemakers and cardiac defibrillators has been reported, and corresponding guidelines have been developed in various countries. Although several studies have reported the effects of radiotherapy in patients with implantable left ventricular assist device (LVAD), its safety remains unclear. Herein, we report three cases of stereotactic ablative radiotherapy (SABR) using CyberKnife for early-stage lung cancer in patients with implantable LVAD.</p><p><strong>Case report: </strong>Three patients in their 50s or 60s, including two women and one man, who had LVADs due to dilated or ischemic cardiomyopathy and performance status of 0 or 1, were diagnosed with stage IA2 lung cancer (cT1bN0M0) by imaging only. All three patients were deemed inoperable due to cardiac comorbidity and underwent SABR at the Osaka University Hospital. The total radiation dose was 42-52 Gy, administered in four fractions. All treatment plans were designed to keep the LVAD dose below 2 Gy. In all patients, SABR was completed without acute adverse events or LVAD malfunction. During the follow-up period of 3-29 months, no disease progression or chronic adverse events were observed in any of the patients.</p><p><strong>Conclusion: </strong>This case series indicated that SABR using CyberKnife is a safe treatment option for early-stage lung cancer in patients with LVAD by reducing the dose to the LVAD.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091694","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}
Background/aim: Nitric oxide (NO) has various physiological activities. In this study, diclofenac (DF) which has a high affinity for human serum albumin (HSA) was nitrosylated to a novel NO donor (NDF). The cytotoxic effects and the mechanism of NDF were investigated.
Materials and methods: Binding experiments of NDF to HSA were performed by the ultrafiltration method. NO was measured by the Griess method. The number of dead cells were measured using annexin V. Apoptosis and endoplasmic reticulum stress were evaluated by western blotting.
Results: NDF competitively inhibits the binding of DF to HSA, suggesting that NDF and DF have equivalent binding characteristics. NDF rapidly released NOx after being dissolved. At 200 μM, NDF induced cell death in human pancreatic cancer cells. Western blotting showed that NDF promoted the cleavage of PARP, caspase-3, and caspase-7. Inhibitors of caspase-1 and caspase-9 significantly suppressed NDF-induced cell death, as did a non-specific caspase inhibitor (Z-VAD). In addition, NDF significantly increased the expression of the endoplasmic reticulum stress marker, CHOP.
Conclusion: NDF induces apoptotic cell death by causing endoplasmic reticulum stress. The findings of this study suggest that NDF may become a promising compound for the treatment of pancreatic cancer.
{"title":"Novel Diclofenac-NO Donor With High Affinity for Human Serum Albumin Induces Endoplasmic Reticulum Stress-mediated Cell Death in Human Pancreatic Cancer Cells.","authors":"Koji Nishi, Ryo Kanda, Kaho Takasaki, Ayano Tamori, Yoshifumi Arimura, Shuhei Imoto, Hirotaka Murase, Kenji Tsukigawa, Masaki Otagiri, Keishi Yamasaki","doi":"10.21873/anticanres.17204","DOIUrl":"https://doi.org/10.21873/anticanres.17204","url":null,"abstract":"<p><strong>Background/aim: </strong>Nitric oxide (NO) has various physiological activities. In this study, diclofenac (DF) which has a high affinity for human serum albumin (HSA) was nitrosylated to a novel NO donor (NDF). The cytotoxic effects and the mechanism of NDF were investigated.</p><p><strong>Materials and methods: </strong>Binding experiments of NDF to HSA were performed by the ultrafiltration method. NO was measured by the Griess method. The number of dead cells were measured using annexin V. Apoptosis and endoplasmic reticulum stress were evaluated by western blotting.</p><p><strong>Results: </strong>NDF competitively inhibits the binding of DF to HSA, suggesting that NDF and DF have equivalent binding characteristics. NDF rapidly released NOx after being dissolved. At 200 μM, NDF induced cell death in human pancreatic cancer cells. Western blotting showed that NDF promoted the cleavage of PARP, caspase-3, and caspase-7. Inhibitors of caspase-1 and caspase-9 significantly suppressed NDF-induced cell death, as did a non-specific caspase inhibitor (Z-VAD). In addition, NDF significantly increased the expression of the endoplasmic reticulum stress marker, CHOP.</p><p><strong>Conclusion: </strong>NDF induces apoptotic cell death by causing endoplasmic reticulum stress. The findings of this study suggest that NDF may become a promising compound for the treatment of pancreatic cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091644","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 : 2024-09-01DOI: 10.21873/anticanres.17212
Jihye Seo, Minseo Park, Sayeon Cho
Background/aim: Hepatocellular carcinoma (HCC) is a main type of liver cancer with high metastatic potential, and its incidence is steadily increasing worldwide. However, the development of new drugs for the treatment of HCC is still insufficient. This study aimed to determine the anticancer effect of NSC-38270, a natural product, on HCC.
Materials and methods: After treating HCC Huh7 cells with NSC-38270, cell growth, wound healing, migration, and invasion assays were conducted. We investigated the effects of NSC-38270 on Twist1, a crucial epithelial-mesenchymal transition (EMT)-related transcription factor. In addition, apoptosis, histone H2A.X activation, and cell morphology assays were performed in Huh7 and immortalized normal liver cells following treatment with NSC-38270.
Results: NSC-38270 reduced the migration and invasion ability of Huh7 cells, accompanied by a decrease in Twist1. Furthermore, NSC-38270 induced apoptosis in Huh7 cells, whereas apoptosis was not observed in immortalized normal liver cells (THLE-2 cells and Chang liver cells).
Conclusion: NSC-38270 exhibited significant inhibitory effects on the migration and invasion of Huh7 cells by repressing Twist1. Importantly, it induced cancer cell-specific apoptotic effects. These findings suggest that NSC-38270 holds promising potential as a therapeutic candidate for cancer treatment.
{"title":"NSC-38270 Exhibits Anti-invasive and Pro-apoptotic Effects on Hepatocellular Carcinoma Huh7 Cells.","authors":"Jihye Seo, Minseo Park, Sayeon Cho","doi":"10.21873/anticanres.17212","DOIUrl":"https://doi.org/10.21873/anticanres.17212","url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) is a main type of liver cancer with high metastatic potential, and its incidence is steadily increasing worldwide. However, the development of new drugs for the treatment of HCC is still insufficient. This study aimed to determine the anticancer effect of NSC-38270, a natural product, on HCC.</p><p><strong>Materials and methods: </strong>After treating HCC Huh7 cells with NSC-38270, cell growth, wound healing, migration, and invasion assays were conducted. We investigated the effects of NSC-38270 on Twist1, a crucial epithelial-mesenchymal transition (EMT)-related transcription factor. In addition, apoptosis, histone H2A.X activation, and cell morphology assays were performed in Huh7 and immortalized normal liver cells following treatment with NSC-38270.</p><p><strong>Results: </strong>NSC-38270 reduced the migration and invasion ability of Huh7 cells, accompanied by a decrease in Twist1. Furthermore, NSC-38270 induced apoptosis in Huh7 cells, whereas apoptosis was not observed in immortalized normal liver cells (THLE-2 cells and Chang liver cells).</p><p><strong>Conclusion: </strong>NSC-38270 exhibited significant inhibitory effects on the migration and invasion of Huh7 cells by repressing Twist1. Importantly, it induced cancer cell-specific apoptotic effects. These findings suggest that NSC-38270 holds promising potential as a therapeutic candidate for cancer treatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091645","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}
Background/aim: Carbon-ion radiotherapy (CiRT) has been used for the treatment of locally advanced pancreatic cancer (LAPC) with uniform dose plan. The aim of the present study is to investigate the effectiveness of a simultaneous integrated boost (SIB) technique with scanned CiRT against LAPC.
Materials and methods: Data of 21 patients with LAPC were used to compare two treatment planning approaches: a conventional uniform dose approach and a SIB approach. A relative biological effectiveness (RBE)-weighted dose (DRBE) of 55.2 Gy (RBE) in 12 fractions was prescribed to the planning target volume (PTV) in the conventional approach. In the SIB approach, DRBE of 67.2 Gy (RBE) and 43.2 Gy (RBE) in 12 fractions were prescribed to a high-risk PTV (HR-PTV) and low-risk PTV (LR-PTV), respectively. The DRBE and dose-averaged linear energy transfer (LETd) of targets and gastrointestinal tracts as organs at risk (OARs) were evaluated.
Results: The HR-PTV D90% and LR-PTV D90% were 64.4±0.6 and 42.5±0.1 Gy (RBE) in SIB approach compared to the PTV D90% of 54.1±0.4 Gy (RBE) in the conventional approach. All SIB plans achieved the D2cc lower than 46 Gy (RBE) and V30 lower than 4 cm3 within OARs. The SIB approach increased the minimum LETd within the GTV to 44 keV/μm or higher for 20 out of 21 patients as compared to 16 out of 21 patients in the conventional approach.
Conclusion: The SIB approach effectively increased the RBE-weighted dose and LETd within the HR-PTV and GTV by accumulating the high-LET stopping carbon-ions into the HR-PTV in addition to the decreased RBE-weighted dose to OARs.
{"title":"<i>In Silico</i> Study of Simultaneous Integrated Boost Carbon-Ion Radiotherapy for Locally Advanced Pancreatic Cancer.","authors":"Taku Nakaji, Makoto Shinoto, Shigeru Yamada, Taku Inaniwa","doi":"10.21873/anticanres.17208","DOIUrl":"https://doi.org/10.21873/anticanres.17208","url":null,"abstract":"<p><strong>Background/aim: </strong>Carbon-ion radiotherapy (CiRT) has been used for the treatment of locally advanced pancreatic cancer (LAPC) with uniform dose plan. The aim of the present study is to investigate the effectiveness of a simultaneous integrated boost (SIB) technique with scanned CiRT against LAPC.</p><p><strong>Materials and methods: </strong>Data of 21 patients with LAPC were used to compare two treatment planning approaches: a conventional uniform dose approach and a SIB approach. A relative biological effectiveness (RBE)-weighted dose (D<sub>RBE</sub>) of 55.2 Gy (RBE) in 12 fractions was prescribed to the planning target volume (PTV) in the conventional approach. In the SIB approach, D<sub>RBE</sub> of 67.2 Gy (RBE) and 43.2 Gy (RBE) in 12 fractions were prescribed to a high-risk PTV (HR-PTV) and low-risk PTV (LR-PTV), respectively. The D<sub>RBE</sub> and dose-averaged linear energy transfer (LET<sub>d</sub>) of targets and gastrointestinal tracts as organs at risk (OARs) were evaluated.</p><p><strong>Results: </strong>The HR-PTV D<sub>90%</sub> and LR-PTV D<sub>90%</sub> were 64.4±0.6 and 42.5±0.1 Gy (RBE) in SIB approach compared to the PTV D<sub>90%</sub> of 54.1±0.4 Gy (RBE) in the conventional approach. All SIB plans achieved the D<sub>2cc</sub> lower than 46 Gy (RBE) and V<sub>30</sub> lower than 4 cm<sup>3</sup> within OARs. The SIB approach increased the minimum LET<sub>d</sub> within the GTV to 44 keV/μm or higher for 20 out of 21 patients as compared to 16 out of 21 patients in the conventional approach.</p><p><strong>Conclusion: </strong>The SIB approach effectively increased the RBE-weighted dose and LET<sub>d</sub> within the HR-PTV and GTV by accumulating the high-LET stopping carbon-ions into the HR-PTV in addition to the decreased RBE-weighted dose to OARs.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091632","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}
Background/aim: Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment modality that selectively kills cancer cells and may induce a therapeutic host immune response. The aim of this study was to determine the feasibility of combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy for unresectable recurrent head and neck cancer.
Patients and methods: Five patients underwent NIR-PIT at Ryukyu University Hospital between January 2022 and April 2024. These patients had unresectable recurrent head and neck squamous cell carcinoma. Among these five patients, four received a combination NIR-PIT and pembrolizumab administration.
Results: A total of seven lesions in the oropharynx and oral cavity were targeted. One patient was treated for three different target lesions. The best observed response (BOR) rate was 100%, with three complete responses and four partial responses. The most common treatment-related adverse event was Grade 1 or 2 local pain lasting one to two days postoperatively, which occurred in all patients. Grade 3 adverse events occurred in three cases (42.9%), including pneumonia, pharynx-cutaneous fistula, and trismus. Three patients received ICI therapy following NIR-PIT, achieving a 60% BOR rate. No immune-related adverse events were noted, and the aforementioned Grade 3 adverse events did not worsen during ICI therapy. At a median follow-up of 376 days (range=157-845 days), four target lesions showed no recurrence, while three had recurred. All five patients were alive, including three with no evidence of disease.
Conclusion: The combination of NIR-PIT and ICI therapy for unresectable recurrent head and neck cancer was feasible.
{"title":"Feasibility of Near-infrared Photoimmunotherapy Combined With Immune Checkpoint Inhibitor Therapy in Unresectable Head and Neck Cancer.","authors":"Hitoshi Hirakawa, Taro Ikegami, Hidetoshi Kinjyo, Yoshikazu Hayashi, Shinya Agena, Teruyuki Higa, Shunsuke Kondo, Masatomo Toyama, Hiroyuki Maeda, Mikio Suzuki","doi":"10.21873/anticanres.17218","DOIUrl":"https://doi.org/10.21873/anticanres.17218","url":null,"abstract":"<p><strong>Background/aim: </strong>Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment modality that selectively kills cancer cells and may induce a therapeutic host immune response. The aim of this study was to determine the feasibility of combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy for unresectable recurrent head and neck cancer.</p><p><strong>Patients and methods: </strong>Five patients underwent NIR-PIT at Ryukyu University Hospital between January 2022 and April 2024. These patients had unresectable recurrent head and neck squamous cell carcinoma. Among these five patients, four received a combination NIR-PIT and pembrolizumab administration.</p><p><strong>Results: </strong>A total of seven lesions in the oropharynx and oral cavity were targeted. One patient was treated for three different target lesions. The best observed response (BOR) rate was 100%, with three complete responses and four partial responses. The most common treatment-related adverse event was Grade 1 or 2 local pain lasting one to two days postoperatively, which occurred in all patients. Grade 3 adverse events occurred in three cases (42.9%), including pneumonia, pharynx-cutaneous fistula, and trismus. Three patients received ICI therapy following NIR-PIT, achieving a 60% BOR rate. No immune-related adverse events were noted, and the aforementioned Grade 3 adverse events did not worsen during ICI therapy. At a median follow-up of 376 days (range=157-845 days), four target lesions showed no recurrence, while three had recurred. All five patients were alive, including three with no evidence of disease.</p><p><strong>Conclusion: </strong>The combination of NIR-PIT and ICI therapy for unresectable recurrent head and neck cancer was feasible.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091634","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}
Background/aim: Upregulation of matrix metallo-proteinase-8 (MMP-8) serves as a protein-based indicator for predicting nasopharyngeal carcinoma (NPC) metastasis. Nevertheless, the role of MMP-8 genotypes in NPC has never been investigated. This study aimed to explore the involvement of MMP-8 genotypes in NPC development.
Materials and methods: We employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to analyze MMP-8 genotypes, specifically C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072), in a Taiwanese cohort comprising 208 NPC cases and 416 healthy controls.
Results: Individuals with either heterozygous or homozygous variant genotypes of MMP-8 rs11225395 showed no significant change in NPC risk compared to those with the wild-type genotype [odds ratio (OR)=0.97 and 0.79, 95% confidence intervals (95%CI)=0.68-1.38 and 0.46-1.36; p=0.9304 and 0.4736, respectively]. Similarly, there was no significant association between the heterozygous genotypes of MMP-8 rs34009635 and NPC risk (OR=0.66, 95%CI=0.24-1.84; p=0.5738). For MMP-8 rs35866072, all individuals in the study were of the TT genotype. Furthermore, the presence of variant alleles at MMP-8 rs11225395 or rs34009635 did not result in altered NPC risk (OR=0.91 and 0.66, 95%CI=0.71-1.16 and 0.24-1.84, p=0.4876 and 0.5769, respectively). Additionally, no significant association was observed between MMP-8 rs11225395 variant genotypes and NPC risk among individuals regardless of smoking, alcohol consumption, or betel quid chewing habits (all p>0.05).
Conclusion: There was no association between the MMP-8 genotypes rs11225395, rs34009635, or rs35866072 and NPC risk among Taiwanese individuals. Moreover, no combined effects of MMP-8 genotype with smoking, alcohol consumption, or betel quid chewing habits on NPC risk were observed.
{"title":"Impact of Matrix Metalloproteinase-8 Polymorphisms on Nasopharyngeal Carcinoma Risk.","authors":"Chao-Hsuan Chen, Yu-Ting Chin, Shih-Wei Hsu, Liang-Chun Shih, Hui-Chi Tien, Chia-Wen Tsai, Yun-Chi Wang, Yen-Fang Liu, DA-Tian Bau, Wen-Shin Chang","doi":"10.21873/anticanres.17207","DOIUrl":"https://doi.org/10.21873/anticanres.17207","url":null,"abstract":"<p><strong>Background/aim: </strong>Upregulation of matrix metallo-proteinase-8 (MMP-8) serves as a protein-based indicator for predicting nasopharyngeal carcinoma (NPC) metastasis. Nevertheless, the role of MMP-8 genotypes in NPC has never been investigated. This study aimed to explore the involvement of MMP-8 genotypes in NPC development.</p><p><strong>Materials and methods: </strong>We employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to analyze MMP-8 genotypes, specifically C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072), in a Taiwanese cohort comprising 208 NPC cases and 416 healthy controls.</p><p><strong>Results: </strong>Individuals with either heterozygous or homozygous variant genotypes of MMP-8 rs11225395 showed no significant change in NPC risk compared to those with the wild-type genotype [odds ratio (OR)=0.97 and 0.79, 95% confidence intervals (95%CI)=0.68-1.38 and 0.46-1.36; p=0.9304 and 0.4736, respectively]. Similarly, there was no significant association between the heterozygous genotypes of MMP-8 rs34009635 and NPC risk (OR=0.66, 95%CI=0.24-1.84; p=0.5738). For MMP-8 rs35866072, all individuals in the study were of the TT genotype. Furthermore, the presence of variant alleles at MMP-8 rs11225395 or rs34009635 did not result in altered NPC risk (OR=0.91 and 0.66, 95%CI=0.71-1.16 and 0.24-1.84, p=0.4876 and 0.5769, respectively). Additionally, no significant association was observed between MMP-8 rs11225395 variant genotypes and NPC risk among individuals regardless of smoking, alcohol consumption, or betel quid chewing habits (all p>0.05).</p><p><strong>Conclusion: </strong>There was no association between the MMP-8 genotypes rs11225395, rs34009635, or rs35866072 and NPC risk among Taiwanese individuals. Moreover, no combined effects of MMP-8 genotype with smoking, alcohol consumption, or betel quid chewing habits on NPC risk were observed.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091639","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}