Pub Date : 2024-09-01DOI: 10.21873/anticanres.17206
Nitzan Sagie, Elizabeth Romanov, Yarden Kezerle, Amichay Meirovitz, Kim Sheva
Background/aim: Small-cell lung cancer (SCLC) is noted for its high proliferative rate, and while treatable, relapse is common. SCLC is known to potentially express somatostatin receptors (SSTRs). Somatostatin possesses antineoplastic activity through cell-cycle arrest and apoptosis, and angiogenesis inhibition. SSTRs, thus, serve as potential anticancer targets for somatostatin analogue therapies. The aim of the study was to determine the expression rate of SSTR subtypes 1, 2 and 3 in SCLC using immunohistochemistry, and potential predictors of such rates.
Materials and methods: A total of 147 human, SCLC paraffin-embedded tissue microarrays with corresponding patient age, sex, TNM staging, and disease stage were utilized. Immunohistochemical analysis was performed using anti-SSTR 1, 2 and 3 antibodies, each calibrated using healthy human pancreatic islets as positive controls. Array slides were counterstained with hematoxylin and scored based on stain intensity and percentage of stained cells.
Results: No SCLC samples expressed SSTR 1, whereas SSTR 2 and 3 were expressed in 29.4% and 4.35% of cases respectively. While females had higher expression levels of SSTR 2/3, and there was a trend of decreased SSTR 2 expression with increased age, results were not statistically significant. No correlation between disease stage and SSTR expression was found. Co-expression of both SSTR2 and 3 occurred in 5.3% of patients.
Conclusion: Immunohisto-chemistry is an efficient screening tool to reveal optimum SCLC patients for somatostatin analogue therapy. Whilst there currently exist no accepted norm or predictors of SSTR expression levels in SCLC patients, this study contributes insight into the receptors' varied expression.
{"title":"Expression Analysis of SSTR 1, 2 and 3 in Small-cell Lung Cancer Patients as Targets for Future Peptide Receptor Radionuclide Therapy.","authors":"Nitzan Sagie, Elizabeth Romanov, Yarden Kezerle, Amichay Meirovitz, Kim Sheva","doi":"10.21873/anticanres.17206","DOIUrl":"https://doi.org/10.21873/anticanres.17206","url":null,"abstract":"<p><strong>Background/aim: </strong>Small-cell lung cancer (SCLC) is noted for its high proliferative rate, and while treatable, relapse is common. SCLC is known to potentially express somatostatin receptors (SSTRs). Somatostatin possesses antineoplastic activity through cell-cycle arrest and apoptosis, and angiogenesis inhibition. SSTRs, thus, serve as potential anticancer targets for somatostatin analogue therapies. The aim of the study was to determine the expression rate of SSTR subtypes 1, 2 and 3 in SCLC using immunohistochemistry, and potential predictors of such rates.</p><p><strong>Materials and methods: </strong>A total of 147 human, SCLC paraffin-embedded tissue microarrays with corresponding patient age, sex, TNM staging, and disease stage were utilized. Immunohistochemical analysis was performed using anti-SSTR 1, 2 and 3 antibodies, each calibrated using healthy human pancreatic islets as positive controls. Array slides were counterstained with hematoxylin and scored based on stain intensity and percentage of stained cells.</p><p><strong>Results: </strong>No SCLC samples expressed SSTR 1, whereas SSTR 2 and 3 were expressed in 29.4% and 4.35% of cases respectively. While females had higher expression levels of SSTR 2/3, and there was a trend of decreased SSTR 2 expression with increased age, results were not statistically significant. No correlation between disease stage and SSTR expression was found. Co-expression of both SSTR2 and 3 occurred in 5.3% of patients.</p><p><strong>Conclusion: </strong>Immunohisto-chemistry is an efficient screening tool to reveal optimum SCLC patients for somatostatin analogue therapy. Whilst there currently exist no accepted norm or predictors of SSTR expression levels in SCLC patients, this study contributes insight into the receptors' varied expression.</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":"142091633","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: No studies have investigated the advantage of laparoscopic hepatectomy (LH) compared with open hepatectomy (OH) from a nutritional perspective. This study aimed to compare the postoperative nutritional status between LH and OH.
Patients and methods: A total of 186 patients who underwent partial hepatic resection for liver tumors were analyzed retrospectively. We compared perioperative variables between LH and OH. The nutritional status was assessed using serum albumin (Alb) and rapid turnover protein concentrations. We investigated risk factors for postoperative malnutrition using univariate and multivariate analyses.
Results: The LH group, compared with the OH group, had a significantly shorter operative time (239 vs. 344 min, p<0.03), less intraoperative blood loss (100 vs. 343 g, p<0.01), and a shorter length of postoperative stay (8 vs. 11 days, p<0.01). Postoperative serum Alb and prealbumin concentrations in the LH group were significantly higher than those in the OH group (3.4 vs. 3.2 g/dl, p<0.01; 15.0 vs. 12.0 mg/dl, p=0.02, respectively). The multivariate analysis showed that OH (p=0.02) and hepatocellular carcinoma (p<0.01) were significant and independent risk factors for postoperative malnutrition.
Conclusion: LH may be superior to OH in terms of the postoperative nutritional status, intraoperative blood loss, and length of postoperative stay.
{"title":"Postoperative Nutritional Assessment of Laparoscopic <i>Versus</i> Open Partial Hepatectomy.","authors":"Kenei Furukawa, Masashi Tsunematsu, Koichiro Haruki, Shinji Onda, Tomohiko Taniai, Kyohei Abe, Yoshihiro Shirai, Yuta Yamada, Toru Ikegami","doi":"10.21873/anticanres.17221","DOIUrl":"https://doi.org/10.21873/anticanres.17221","url":null,"abstract":"<p><strong>Background/aim: </strong>No studies have investigated the advantage of laparoscopic hepatectomy (LH) compared with open hepatectomy (OH) from a nutritional perspective. This study aimed to compare the postoperative nutritional status between LH and OH.</p><p><strong>Patients and methods: </strong>A total of 186 patients who underwent partial hepatic resection for liver tumors were analyzed retrospectively. We compared perioperative variables between LH and OH. The nutritional status was assessed using serum albumin (Alb) and rapid turnover protein concentrations. We investigated risk factors for postoperative malnutrition using univariate and multivariate analyses.</p><p><strong>Results: </strong>The LH group, compared with the OH group, had a significantly shorter operative time (239 vs. 344 min, p<0.03), less intraoperative blood loss (100 vs. 343 g, p<0.01), and a shorter length of postoperative stay (8 vs. 11 days, p<0.01). Postoperative serum Alb and prealbumin concentrations in the LH group were significantly higher than those in the OH group (3.4 vs. 3.2 g/dl, p<0.01; 15.0 vs. 12.0 mg/dl, p=0.02, respectively). The multivariate analysis showed that OH (p=0.02) and hepatocellular carcinoma (p<0.01) were significant and independent risk factors for postoperative malnutrition.</p><p><strong>Conclusion: </strong>LH may be superior to OH in terms of the postoperative nutritional status, intraoperative blood loss, and length of postoperative stay.</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":"142091651","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 study aimed to investigate the efficacy of radiotherapy or chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer.
Patients and methods: Twenty-eight patients who had isolated locoregional recurrence after pancreatectomy for pancreatic cancer between 2007 and 2021 were retrospectively analyzed. We investigated the effect of the treatment method [radiotherapy or chemoradiotherapy (radiotherapy with concurrent chemotherapy)] on progression-free survival (PFS) and post-recurrence survival (PRS).
Results: The median disease-free survival was 16.1 months (range=4.7-47.1 months). Five patients received radiotherapy and 21 patients received chemoradiotherapy [radiotherapy concurrent with gemcitabine (GEM) or S-1] for locoregional recurrence. All patients except one patient with interstitial pneumonia were treated with salvage chemotherapy after irradiation. The median PFS rates of the radiotherapy group and the chemoradiotherapy group were 2.8 months (range=1.5-5.4 months) and 16.8 months (range=2.7-42.8 months), respectively. The median PRS rates were 23.7 months (range=8.1-26.4 months) for the radiotherapy group and 26.2 months (range=6.0-64.7 months) for the chemoradiotherapy group. Multivariate analysis identified radiotherapy [hazard ratio (HR)=12.2, 95% confidence interval (CI)=3.29-45.6, p<0.001] and serum DUPAN-2 >150 U/ml (HR=2.90, 95%CI=1.22-6.93, p=0.02) as independent predictors of PFS, and UICC TNM Stage ≥III (HR=3.23, 95%CI=1.17-8.96, p=0.02) and modified Glasgow prognostic score before the treatment for the recurrence 1 or 2 (HR=3.05, 95%CI=1.15-8.08, p=0.03) as independent predictors of PRS.
Conclusion: Chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer could suppress re-recurrence more effectively than radiotherapy.
{"title":"Effect of Chemoradiotherapy on Locoregional Recurrence After Pancreatectomy for Pancreatic Cancer.","authors":"Michinori Matsumoto, Kenei Furukawa, Tadashi Uwagawa, Yoshihiro Shirai, Masashi Tsunematsu, Shinji Onda, Takeshi Gocho, Yuta Yamada, Koichiro Haruki, Toru Ikegami","doi":"10.21873/anticanres.17229","DOIUrl":"https://doi.org/10.21873/anticanres.17229","url":null,"abstract":"<p><strong>Background/aim: </strong>The study aimed to investigate the efficacy of radiotherapy or chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer.</p><p><strong>Patients and methods: </strong>Twenty-eight patients who had isolated locoregional recurrence after pancreatectomy for pancreatic cancer between 2007 and 2021 were retrospectively analyzed. We investigated the effect of the treatment method [radiotherapy or chemoradiotherapy (radiotherapy with concurrent chemotherapy)] on progression-free survival (PFS) and post-recurrence survival (PRS).</p><p><strong>Results: </strong>The median disease-free survival was 16.1 months (range=4.7-47.1 months). Five patients received radiotherapy and 21 patients received chemoradiotherapy [radiotherapy concurrent with gemcitabine (GEM) or S-1] for locoregional recurrence. All patients except one patient with interstitial pneumonia were treated with salvage chemotherapy after irradiation. The median PFS rates of the radiotherapy group and the chemoradiotherapy group were 2.8 months (range=1.5-5.4 months) and 16.8 months (range=2.7-42.8 months), respectively. The median PRS rates were 23.7 months (range=8.1-26.4 months) for the radiotherapy group and 26.2 months (range=6.0-64.7 months) for the chemoradiotherapy group. Multivariate analysis identified radiotherapy [hazard ratio (HR)=12.2, 95% confidence interval (CI)=3.29-45.6, p<0.001] and serum DUPAN-2 >150 U/ml (HR=2.90, 95%CI=1.22-6.93, p=0.02) as independent predictors of PFS, and UICC TNM Stage ≥III (HR=3.23, 95%CI=1.17-8.96, p=0.02) and modified Glasgow prognostic score before the treatment for the recurrence 1 or 2 (HR=3.05, 95%CI=1.15-8.08, p=0.03) as independent predictors of PRS.</p><p><strong>Conclusion: </strong>Chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer could suppress re-recurrence more effectively than radiotherapy.</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":"142091537","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: We herein examined T cell immunity in esophageal cancer patients with and without Helicobacter pylori infection to establish a foundation for immunotherapeutic strategies targeting esophageal cancer in the presence of H. pylori infection.
Materials and methods: Twenty-six patients with esophageal squamous cell carcinoma between 2015 and 2017 were enrolled in the present study. Serum antibodies against H. pylori were measured. Fresh tumor tissues were obtained by endoscopic biopsy or from surgical resection. A cell suspension of these tissues was subjected to a flow cytometric analysis.
Results: Among the 26 patients analyzed, 10 (38.5%) were seropositive for H. pylori. The flow cytometric analysis of tumor-infiltrating lymphocytes revealed that the percentage of CD103+CD4+ T cells in esophageal tumors was significantly lower in H. pylori-positive patients than in H. pylori-negative patients (p=0.0105). Conversely, the percentage of CD45RA-CD25hi effector Treg cells in esophageal tumors was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (p=0.0022), indicating an immunosuppressive tumor microenvironment in the former. Following neoadjuvant chemotherapy, the number of CD45RA-CD25hi effector Treg cells decreased (p=0.0248).
Conclusion: The tumor immune microenvironment of esophageal cancer patients with H. pylori infection exhibited an immunosuppressive phenotype. The targeting of Treg cells has potential in immunotherapy for this patient population.
背景/目的:我们在此研究了幽门螺杆菌感染和未感染幽门螺杆菌的食管癌患者的T细胞免疫,为幽门螺杆菌感染情况下针对食管癌的免疫治疗策略奠定基础:本研究共纳入了26例2015年至2017年间的食管鳞状细胞癌患者。测定了血清中的幽门螺杆菌抗体。通过内镜活检或手术切除获得新鲜肿瘤组织。对这些组织的细胞悬液进行流式细胞分析:在分析的 26 名患者中,10 人(38.5%)幽门螺杆菌血清反应呈阳性。肿瘤浸润淋巴细胞的流式细胞分析显示,幽门螺杆菌阳性患者食管肿瘤中 CD103+CD4+ T 细胞的比例明显低于幽门螺杆菌阴性患者(P=0.0105)。相反,幽门螺杆菌阳性患者食管肿瘤中CD45RA-CD25hi效应Treg细胞的比例明显高于幽门螺杆菌阴性患者(p=0.0022),表明前者存在免疫抑制性肿瘤微环境。新辅助化疗后,CD45RA-CD25hi效应Treg细胞数量减少(p=0.0248):结论:幽门螺杆菌感染的食管癌患者的肿瘤免疫微环境表现出免疫抑制表型。以Treg细胞为靶点的免疫疗法在这类患者中具有潜力。
{"title":"<i>Helicobacter pylori</i> Infection Affects the Tumor Immune Microenvironment of Esophageal Cancer Patients.","authors":"Hiroki Matsuda, Kota Iwahori, Tomohira Takeoka, Ryo Kato, Shinya Urakawa, Takuro Saito, Tomoki Makino, Hidetoshi Eguchi, Yuichiro Doki, Hisashi Wada","doi":"10.21873/anticanres.17205","DOIUrl":"https://doi.org/10.21873/anticanres.17205","url":null,"abstract":"<p><strong>Background/aim: </strong>We herein examined T cell immunity in esophageal cancer patients with and without Helicobacter pylori infection to establish a foundation for immunotherapeutic strategies targeting esophageal cancer in the presence of H. pylori infection.</p><p><strong>Materials and methods: </strong>Twenty-six patients with esophageal squamous cell carcinoma between 2015 and 2017 were enrolled in the present study. Serum antibodies against H. pylori were measured. Fresh tumor tissues were obtained by endoscopic biopsy or from surgical resection. A cell suspension of these tissues was subjected to a flow cytometric analysis.</p><p><strong>Results: </strong>Among the 26 patients analyzed, 10 (38.5%) were seropositive for H. pylori. The flow cytometric analysis of tumor-infiltrating lymphocytes revealed that the percentage of CD103<sup>+</sup>CD4<sup>+</sup> T cells in esophageal tumors was significantly lower in H. pylori-positive patients than in H. pylori-negative patients (p=0.0105). Conversely, the percentage of CD45RA-CD25hi effector Treg cells in esophageal tumors was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (p=0.0022), indicating an immunosuppressive tumor microenvironment in the former. Following neoadjuvant chemotherapy, the number of CD45RA-CD25hi effector Treg cells decreased (p=0.0248).</p><p><strong>Conclusion: </strong>The tumor immune microenvironment of esophageal cancer patients with H. pylori infection exhibited an immunosuppressive phenotype. The targeting of Treg cells has potential in immunotherapy for this patient population.</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":"142091631","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 predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear.
Patients and methods: We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders.
Results: In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response.
Conclusion: Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab.
{"title":"Role of Hematological Markers in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Treated With Pembrolizumab.","authors":"Kohei Hagiwara, Takashi Matsuki, Takuro Okada, Chihiro Fushimi, Takahito Kondo, Hideaki Takahashi, Isaku Okamoto, Kunihiko Tokashiki, Kenji Hanyu, Takuma Kishida, Tatsuya Ito, Gai Yamashita, Kiyoaki Tsukahara, Tatsuo Masubuchi, Yuichiro Tada, Kaho Momiyama, Ryohei Yaguchi, Nobuhiko Oridate, G O Omura, Taku Yamashita","doi":"10.21873/anticanres.17235","DOIUrl":"https://doi.org/10.21873/anticanres.17235","url":null,"abstract":"<p><strong>Background/aim: </strong>The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear.</p><p><strong>Patients and methods: </strong>We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders.</p><p><strong>Results: </strong>In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response.</p><p><strong>Conclusion: </strong>Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab.</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":"142091674","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.17220
Kunihide Mohri, Hidenari Nagai, Takahisa Matsuda, Yoshinori Igarashi, Koji Higai
Background/aim: Atezolizumab plus beva-cizumab (AteBev) are an integral part of first-line therapy for unresectable hepatocellular carcinoma (uHCC), whereas no second-line regimen has been developed for these patients. This study evaluated the efficacy of second-line therapy for uHCC following AteBev treatment.
Patients and methods: Sixty uHCC patients who were administered AteBev therapy were included in the study. Dynamic computed tomography was conducted after 6, 9, and 12 weeks, and blood tests were performed at baseline and after three weeks.
Results: After six weeks of AteBev therapy, 19 patients experienced partial response (PR), 12 had stable disease (SD), and 29 exhibited progressive disease (PD), with an overall response rate (ORR) of 31.7%. Of the 21 patients treated with lenvatinib as second-line treatment, one dropped out, nine experienced a compete response (CR) or PR, and 11 had SD or PD, resulting in an ORR of 45.0%. Serum levels of fibroblast growth factors (FGF)-19 increased substantially following lenvatinib therapy in the CR+PR group, although the levels decreased significantly in the SD+PD group. Soluble FGF-R4 levels did not differ significantly between the CR+PR group and the SD+PD group when assessed before and after lenvatinib treatment.
Conclusion: Lenvatinib is useful as second-line treatment after Ate/Bev for uHCC patients who do not response to Ate/Bev treatment. Changes in serum FGF-19 levels after three weeks of AteBev therapy may serve as a biomarker for selecting lenvatinib as second-line therapy.
{"title":"Second-line Treatment Strategy in Unresectable Hepatocellular Carcinoma After First-line Atezolizumab Plus Bevacizumab.","authors":"Kunihide Mohri, Hidenari Nagai, Takahisa Matsuda, Yoshinori Igarashi, Koji Higai","doi":"10.21873/anticanres.17220","DOIUrl":"https://doi.org/10.21873/anticanres.17220","url":null,"abstract":"<p><strong>Background/aim: </strong>Atezolizumab plus beva-cizumab (AteBev) are an integral part of first-line therapy for unresectable hepatocellular carcinoma (uHCC), whereas no second-line regimen has been developed for these patients. This study evaluated the efficacy of second-line therapy for uHCC following AteBev treatment.</p><p><strong>Patients and methods: </strong>Sixty uHCC patients who were administered AteBev therapy were included in the study. Dynamic computed tomography was conducted after 6, 9, and 12 weeks, and blood tests were performed at baseline and after three weeks.</p><p><strong>Results: </strong>After six weeks of AteBev therapy, 19 patients experienced partial response (PR), 12 had stable disease (SD), and 29 exhibited progressive disease (PD), with an overall response rate (ORR) of 31.7%. Of the 21 patients treated with lenvatinib as second-line treatment, one dropped out, nine experienced a compete response (CR) or PR, and 11 had SD or PD, resulting in an ORR of 45.0%. Serum levels of fibroblast growth factors (FGF)-19 increased substantially following lenvatinib therapy in the CR+PR group, although the levels decreased significantly in the SD+PD group. Soluble FGF-R4 levels did not differ significantly between the CR+PR group and the SD+PD group when assessed before and after lenvatinib treatment.</p><p><strong>Conclusion: </strong>Lenvatinib is useful as second-line treatment after Ate/Bev for uHCC patients who do not response to Ate/Bev treatment. Changes in serum FGF-19 levels after three weeks of AteBev therapy may serve as a biomarker for selecting lenvatinib as second-line therapy.</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":"142091690","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.17210
Y U Gao, Sophia Wendt, Saskia Krohn, Moosheer Alammar, Christian Junghanss, Ingo Nolte, Hugo Murua Escobar
Background/aim: Uveal melanoma (UM) represents a prevailing primary intraocular malignancy, with a limited median overall survival among metastatic patients, and most tumors lack RAF/RAS mutations. The pan-RAF inhibitor LY3009120 has demonstrated valuable anti-tumor effects in a wide range of RAF/RASmut and wild-type (WT) tumor models. This study aimed to evaluate the antitumor effect of LY3009120 on 92-1 UM cell line.
Materials and methods: The effect of the pan-RAF inhibitor LY3009120 on cell proliferation, metabolic activity, biomass, early and late apoptosis/necrosis, and morphology was characterized in vitro (0.1-5 μM for 48 h/72 h). Furthermore, targeted panel sequencing was used to characterize the mutational landscape of the human 92-1 UM cell line.
Results: LY3009120 showed a significant concentration-dependent anti-proliferative effect on 92-1 cells. Cell proliferation and viability were significantly reduced at the lowest effective concentration of 0.5 μM (at 48 and 72 h, p<0.001). Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in 92-1 cells at 5 μM. Except for TP53, NGS showed that all 49 additional analysed genes (Oncomine myeloid panel) of 92-1 were wild-type, including BRAF, NRAS, and KRAS.
Conclusion: The pan-RAF inhibitor LY3009120 demonstrated a significant anti-tumor effect on human UM cell line 92-1 independent of the molecular BRAF and RAS mutational status.
背景/目的:葡萄膜黑色素瘤(UM)是一种常见的原发性眼内恶性肿瘤,转移患者的中位总生存期有限,而且大多数肿瘤缺乏RAF/RAS突变。泛RAF抑制剂LY3009120已在多种RAF/RAS突变和野生型(WT)肿瘤模型中显示出宝贵的抗肿瘤作用。本研究旨在评估 LY3009120 对 92-1 UM 细胞系的抗肿瘤作用:体外研究了泛RAF抑制剂LY3009120对细胞增殖、代谢活性、生物量、早期和晚期细胞凋亡/坏死以及形态学的影响(0.1-5 μM,48小时/72小时)。此外,还使用了靶向面板测序来描述人 92-1 UM 细胞系的突变情况:结果:LY3009120对92-1细胞具有显著的浓度依赖性抗增殖作用。在最低有效浓度 0.5 μM 时,细胞增殖和存活率显著降低(48 小时和 72 小时,pCG):泛 RAF 抑制剂 LY3009120 对人 UM 细胞株 92-1 有明显的抗肿瘤作用,不受 BRAF 和 RAS 分子突变状态的影响。
{"title":"Evaluation of Pan-RAF Inhibitor LY3009120 on Human Uveal Melanoma Cell Line 92-1.","authors":"Y U Gao, Sophia Wendt, Saskia Krohn, Moosheer Alammar, Christian Junghanss, Ingo Nolte, Hugo Murua Escobar","doi":"10.21873/anticanres.17210","DOIUrl":"https://doi.org/10.21873/anticanres.17210","url":null,"abstract":"<p><strong>Background/aim: </strong>Uveal melanoma (UM) represents a prevailing primary intraocular malignancy, with a limited median overall survival among metastatic patients, and most tumors lack RAF/RAS mutations. The pan-RAF inhibitor LY3009120 has demonstrated valuable anti-tumor effects in a wide range of RAF/RASmut and wild-type (WT) tumor models. This study aimed to evaluate the antitumor effect of LY3009120 on 92-1 UM cell line.</p><p><strong>Materials and methods: </strong>The effect of the pan-RAF inhibitor LY3009120 on cell proliferation, metabolic activity, biomass, early and late apoptosis/necrosis, and morphology was characterized in vitro (0.1-5 μM for 48 h/72 h). Furthermore, targeted panel sequencing was used to characterize the mutational landscape of the human 92-1 UM cell line.</p><p><strong>Results: </strong>LY3009120 showed a significant concentration-dependent anti-proliferative effect on 92-1 cells. Cell proliferation and viability were significantly reduced at the lowest effective concentration of 0.5 μM (at 48 and 72 h, p<0.001). Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in 92-1 cells at 5 μM. Except for TP53, NGS showed that all 49 additional analysed genes (Oncomine myeloid panel) of 92-1 were wild-type, including BRAF, NRAS, and KRAS.</p><p><strong>Conclusion: </strong>The pan-RAF inhibitor LY3009120 demonstrated a significant anti-tumor effect on human UM cell line 92-1 independent of the molecular BRAF and RAS mutational status.</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":"142091540","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.17216
Motokazu Sato, Toshihiko Sato, Chihiro Hozumi, Qinghong Han, Kohei Mizuta, Sei Morinaga, Byung Mo Kang, Noritoshi Kobayashi, Yasushi Ichikawa, Atsushi Nakajima, Robert M Hoffman
Background/aim: Positron emission tomography (PET) is an important imaging modality, especially in oncology. [18F]fluorodeoxyglucose PET (FDG-PET) is the most used cancer PET imaging. However, since the elevated glucose use by cancers, termed the Warburg effect, is usually only moderate, FDG often does not provide a strong or well-delineated signal. Malignancies have a stronger addiction to methionine, known as the Hoffman effect, and thus [11C]methionine PET (MET-PET) has demonstrated superiority over FDG-PET in gliomas and other brain tumors. Our team is pioneering the use of MET-PET for tumors of the trunk for both better detection of cancer and to determine candidates for methionine-restriction therapy. The present study provides examples of cancers of organs in the trunk in which MET-PET outperforms FDG-PET in detecting and delineating primary and metastatic cancer.
Patients and methods: In all cases, MET-PET and FDG-PET were performed simultaneously. An evaluation of the images was conducted by a nuclear medicine physician.
Results: Four cases, including prostate, bladder, esophageal, and breast cancer demonstrated the superiority of MET-PET compared to FDG-PET.
Conclusion: MET-PET can out-perform FDG PET for accurate detection of primary and metastatic cancer in the trunk and can determine the extent of methionine addiction of cancer, thereby indicating whether cancer patients can benefit from methionine-restriction therapy.
{"title":"[<sup>11</sup>C]Methionine PET <i>vs</i>. [<sup>18</sup>F]Fluorodeoxyglucose PET Whole-body Imaging to Determine the Extent of Methionine-addiction Compared to Glucose-addiction of Primary and Metastatic Cancer of the Trunk in Patients.","authors":"Motokazu Sato, Toshihiko Sato, Chihiro Hozumi, Qinghong Han, Kohei Mizuta, Sei Morinaga, Byung Mo Kang, Noritoshi Kobayashi, Yasushi Ichikawa, Atsushi Nakajima, Robert M Hoffman","doi":"10.21873/anticanres.17216","DOIUrl":"https://doi.org/10.21873/anticanres.17216","url":null,"abstract":"<p><strong>Background/aim: </strong>Positron emission tomography (PET) is an important imaging modality, especially in oncology. [<sup>18</sup>F]fluorodeoxyglucose PET (FDG-PET) is the most used cancer PET imaging. However, since the elevated glucose use by cancers, termed the Warburg effect, is usually only moderate, FDG often does not provide a strong or well-delineated signal. Malignancies have a stronger addiction to methionine, known as the Hoffman effect, and thus [<sup>11</sup>C]methionine PET (MET-PET) has demonstrated superiority over FDG-PET in gliomas and other brain tumors. Our team is pioneering the use of MET-PET for tumors of the trunk for both better detection of cancer and to determine candidates for methionine-restriction therapy. The present study provides examples of cancers of organs in the trunk in which MET-PET outperforms FDG-PET in detecting and delineating primary and metastatic cancer.</p><p><strong>Patients and methods: </strong>In all cases, MET-PET and FDG-PET were performed simultaneously. An evaluation of the images was conducted by a nuclear medicine physician.</p><p><strong>Results: </strong>Four cases, including prostate, bladder, esophageal, and breast cancer demonstrated the superiority of MET-PET compared to FDG-PET.</p><p><strong>Conclusion: </strong>MET-PET can out-perform FDG PET for accurate detection of primary and metastatic cancer in the trunk and can determine the extent of methionine addiction of cancer, thereby indicating whether cancer patients can benefit from methionine-restriction therapy.</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":"142091630","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.17214
Shuhei Suzuki, Chifumi Kitanaka, Masashi Okada
Background/aim: Glioblastoma is the most aggressive form of brain tumor and has a dismal prognosis; therefore, novel therapeutic approaches based on the mechanisms underlying its aggressive nature are urgently required. A growing body of evidence suggests that neurotransmitters play a key role in modulating the biology of glioblastoma; however, the role of melanocortins remains unclear.
Materials and methods: The effects of bremelanotide, a melanocortin receptor agonist, alone or in combination with chemotherapeutic agents, on survivin expression and cell viability were investigated in human glioblastoma cell lines.
Results: Bremelanotide reduced survivin expression and induced cell death in glioblastoma cells at concentrations that were not toxic to normal human cells, and both of these effects were canceled in the presence of an antagonist of melanocortin receptors 3 and 4. Bremelanotide-induced cell death was prevented by the forced over-expression of survivin in glioblastoma cells, suggesting that bremelanotide induces glioblastoma cell death by inhibiting the expression of survivin. Bremelanotide also promoted cell death induced by chemotherapeutic agents, such as temozolomide and osimertinib.
Conclusion: The present results identified melanocortin receptors 3 and 4 as novel and viable therapeutic targets for glioblastoma. Activation of these receptors by bremelanotide may inhibit the expression of survivin, thereby sensitizing glioblastoma cells to cell death.
{"title":"Melanocortin Receptor Agonist Bremelanotide Induces Cell Death and Growth Inhibition in Glioblastoma Cells <i>via</i> Suppression of Survivin Expression.","authors":"Shuhei Suzuki, Chifumi Kitanaka, Masashi Okada","doi":"10.21873/anticanres.17214","DOIUrl":"https://doi.org/10.21873/anticanres.17214","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastoma is the most aggressive form of brain tumor and has a dismal prognosis; therefore, novel therapeutic approaches based on the mechanisms underlying its aggressive nature are urgently required. A growing body of evidence suggests that neurotransmitters play a key role in modulating the biology of glioblastoma; however, the role of melanocortins remains unclear.</p><p><strong>Materials and methods: </strong>The effects of bremelanotide, a melanocortin receptor agonist, alone or in combination with chemotherapeutic agents, on survivin expression and cell viability were investigated in human glioblastoma cell lines.</p><p><strong>Results: </strong>Bremelanotide reduced survivin expression and induced cell death in glioblastoma cells at concentrations that were not toxic to normal human cells, and both of these effects were canceled in the presence of an antagonist of melanocortin receptors 3 and 4. Bremelanotide-induced cell death was prevented by the forced over-expression of survivin in glioblastoma cells, suggesting that bremelanotide induces glioblastoma cell death by inhibiting the expression of survivin. Bremelanotide also promoted cell death induced by chemotherapeutic agents, such as temozolomide and osimertinib.</p><p><strong>Conclusion: </strong>The present results identified melanocortin receptors 3 and 4 as novel and viable therapeutic targets for glioblastoma. Activation of these receptors by bremelanotide may inhibit the expression of survivin, thereby sensitizing glioblastoma cells to cell death.</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":"142091643","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}