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1.
Ann Surg Oncol ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225857

RESUMEN

BACKGROUND: There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers. METHODS: This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases. RESULTS: CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b. CONCLUSIONS: The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS.

2.
Oncology ; : 1-17, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39265540

RESUMEN

INTRODUCTION: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors. METHODS: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index (PNI), and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment. RESULTS: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease (SD)/progressive disease (PD) group significantly increased (p=0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased. CONCLUSION: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy.

3.
Int J Clin Oncol ; 28(9): 1166-1175, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37368093

RESUMEN

BACKGROUND: Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years. METHODS: Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival. RESULTS: The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death. CONCLUSIONS: NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.


Asunto(s)
Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Anciano , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Oxaliplatino , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/cirugía , Quimioterapia Adyuvante , Gastrectomía
4.
Surg Today ; 53(5): 545-553, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35576018

RESUMEN

The "bystander effect" is a transmission phenomenon mediating communication from target to non-target cells, as well as cell-to-cell interactions between neighboring and distantly located cells. In this narrative review, we describe the fundamental and clinical significance of the bystander effect with respect to cell-to-cell interactions in carcinogenesis, therapeutic response, and tissue regeneration. In carcinogenesis, the bystander effect mediates communications between tumor microenvironments and non-malignant epithelial cells and has been suggested to impact heterogeneous tumorigenic cells in tumors and cancerized fields. In therapeutic response, the bystander effect mediates communications between drug-sensitive and drug-resistant cells and may transmit both drug efficacy and resistance. Therefore, control of therapeutic response transmission via the bystander effect might offer a promising future cancer treatment. Finally, in tissue regeneration, circulating cells and stromal cells may differentiate into various cells for the purpose of tissue regeneration under direction of the bystander effect arising from surrounding cells in a defective space. We hope that the findings we present will promote the development of innovative cancer therapies and tissue regeneration methodologies from the viewpoint of cell-to-cell interactions through the bystander effect.


Asunto(s)
Efecto Espectador , Neoplasias , Humanos , Neoplasias/terapia , Comunicación Celular , Carcinogénesis , Microambiente Tumoral
5.
Esophagus ; 20(1): 99-108, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35881278

RESUMEN

BACKGROUND: Previously, the association between tooth loss and prognosis after esophagectomy was reported; however, the presence of periodontal disease has not been assessed. This study investigated the association between the degree of oral hygiene, as evaluated by tooth loss and periodontal disease, and the prognosis of patients with esophageal cancer. METHODS: A total of 163 esophageal cancer patients who underwent surgery with perioperative oral care and examination were enrolled. We assessed the periodontal pocket depth for the presence of periodontal disease and established a periodontal pocket index, defined as the sum of the periodontal pocket depth of the remaining tooth divided by the total count of the remaining teeth. Patients were divided into three groups: Group A (tooth loss < 13 and periodontal pocket index < 3.67); Group B (tooth loss < 13 and periodontal pocket index ≥ 3.67); and Group C (tooth loss ≥ 13). Overall survival and cancer-specific survival were analyzed, and a multivariate analysis was performed. RESULTS: There was a significant difference in the 5-year overall survival rates between the groups (A:B:C = 74.8%:62.8%:50.5%; p = 0.0098), but not in the 5-year cancer-specific survival rates (A:B:C = 80.2%:64.2%:62.2%; p = 0.0849). In multivariate analysis, oral hygiene (tooth loss < 13 and periodontal pocket index ≥ 3.67 + tooth loss ≥ 13; p = 0.041) was a significant independent poor prognostic factor for overall survival. CONCLUSIONS: Oral evaluation, focusing on tooth loss and periodontal disease, is meaningful in predicting the long-term prognosis of postoperative esophageal cancer patients.


Asunto(s)
Neoplasias Esofágicas , Enfermedades Periodontales , Pérdida de Diente , Humanos , Bolsa Periodontal , Higiene Bucal , Estudios Retrospectivos , Neoplasias Esofágicas/cirugía
6.
Ann Surg Oncol ; 29(12): 7400-7406, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35857197

RESUMEN

BACKGROUND: Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS: We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS: Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS: GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.


Asunto(s)
Antineoplásicos Inmunológicos , Neoplasias Gástricas , Antineoplásicos Inmunológicos/farmacología , Biomarcadores , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Multicéntricos como Asunto , Nivolumab/farmacología , Nivolumab/uso terapéutico , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico
7.
Ann Surg Oncol ; 2022 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-35441306

RESUMEN

PAST: The true impact of co-occurring muscle mass reduction and fat accumulation on patients with surgically resected esophageal cancer (EC) remains controversial. PRESENT: The current study defined reduction in muscle mass and excess body adiposity as the ratio of the visceral fat area (VFA) to the psoas muscle area (V/P ratio) on the same axial computed tomography slice at the third lumbar vertebra (L3). A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), larger VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis showed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) of EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio still was significant for EC patients with a BMI lower than 25 kg/m2. FUTURE: A high V/P ratio was an independent prognostic factor for OS of EC patients who underwent surgery, even BMI-defined non-obese EC patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value for EC patients regardless of body composition differences.

8.
Ann Surg Oncol ; 2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35258768

RESUMEN

BACKGROUND: The synergic effects of muscle mass reduction with excess body adiposity in surgically resected esophageal cancer (EC) patients remains controversial, especially in non-obese patients. METHODS: One hundred and six patients with EC who underwent surgery between 2006 and 2014 were included in this study. Reduction in muscle mass and excess body adiposity were defined as the ratio of visceral fat area (VFA) to psoas muscle area (PMA) (V/P ratio) on the same axial computed tomography (CT) slice at the third lumbar vertebra (L3). RESULTS: A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), higher VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis revealed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) in EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio was still significant in EC patients with a BMI < 25. CONCLUSIONS: A high V/P ratio was associated with poor survival in surgically resected EC patients, even in non-obese patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value in EC patients regardless of body composition differences.

9.
BMC Cancer ; 22(1): 22, 2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-34980017

RESUMEN

BACKGROUND: Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. METHODS: Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. RESULTS: The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. CONCLUSION: The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Monitoreo de Drogas/métodos , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
10.
Digestion ; 103(6): 397-403, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35724642

RESUMEN

INTRODUCTION: We evaluated the risk factors for patients with gastric cancer (GC) undergoing total gastrectomy (TG) that predict postoperative complications, including anastomotic leakage, postoperative pneumonia, and heart disease. METHODS: We collected 106 patients who received TG for GC between May 2009 and May 2017 at Gunma University Graduate School of Medicine, including clinicopathologic, surgical, postoperative complication, laboratory test, and physiologic test data. RESULTS: Of 106 patients, 92 (86.8%) had no complications, and 14 (13.2%) had complications. Univariate analyses revealed that a high American Society of Anaesthesiologists physical status (ASA-PS) and neutrophil-lymphocyte ratio (NLR) of ≥3.5 significantly correlated with postoperative complications. Multivariate analyses showed that high ASA-PS was an independent prognostic factor of postoperative complications. The cancer recurrence rate was 34.8% in the noncomplication group and 71.4% in the complication group. CONCLUSION: Patients with postoperative complications are prone to recurrence and poor prognosis. For patients with high-risk GC with poor ASA-PS and high NLR, more thorough perioperative management is essential.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias Gástricas , Humanos , Pronóstico , Estudios Retrospectivos , Recurrencia Local de Neoplasia/etiología , Gastrectomía/efectos adversos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo
11.
Oncology ; 99(1): 15-22, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33113541

RESUMEN

INTRODUCTION: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. OBJECTIVE: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. METHODS: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8+ lymphocytes expressing PD-1 and CD163+ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. RESULTS: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. CONCLUSIONS: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.


Asunto(s)
Antígeno B7-H1/genética , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Gástricas/genética , Plexo Submucoso/metabolismo , Anciano , Antígenos CD/genética , Antígenos de Diferenciación Mielomonocítica/genética , Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de Superficie Celular/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Plexo Submucoso/patología
12.
Oncology ; 99(11): 732-739, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34392246

RESUMEN

INTRODUCTION: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. METHODS: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. RESULTS: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). CONCLUSION: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Resistencia a Antineoplásicos , Fluorouracilo/uso terapéutico , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Tegafur/uso terapéutico , Anciano , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Proteína-1 Reguladora de Fusión/metabolismo , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Fosforilación , Pronóstico , Estudios Prospectivos , Neoplasias Gástricas/cirugía , Serina-Treonina Quinasas TOR/metabolismo
13.
Digestion ; 102(4): 607-614, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33032290

RESUMEN

BACKGROUND: Endoscopic submucosal dissection (ESD) of early esophageal cancer (EC) is becoming more widespread. Post-ESD coagulation syndrome (CS) has been proposed as temporary inflammatory signs that occur during the post-ESD period caused by transmural thermal injury by electrocoagulation. This retrospective study aimed to evaluate the association between chest pain and abnormal levels of inflammatory markers during the post-esophageal ESD period. We also investigate the clinical importance of chest pain to define the post-esophageal ESD CS. METHODS: We examined 42 patients with thoracic EC who underwent ESD. RESULTS: The incidence of chest pain after esophageal ESD is 35.7% and associated with elevation of WBC count on postoperative day 1 (WBC day 1) (p = 0.022). Multivariate logistic regression analysis using the procedure-related factors revealed that WBC day 1 was an independent predictive factor for chest pain (p = 0.034). The elevation of WBC count is associated with the resected esophageal circumference (p for trend = 0.018), specimen size (p = 0.031), and procedural time (p = 0.004). The incidence of post-esophageal ESD CS was estimated ranging from 11.9 to 54.8% using previously reported criteria. CONCLUSIONS: The incidence of chest pain after ESD was only associated with postoperative elevation of WBC day 1. In considering the elevation of WBC count associated with procedure-related factors, chest pain possibly reflected transmural thermal injury by electrocoagulation during ESD. Post-esophageal ESD chest pain is a simple and clinically useful surrogate marker for transmural thermal injury and is a vital sign of post-esophageal ESD CS.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Biomarcadores , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/epidemiología , Dolor en el Pecho/etiología , Electrocoagulación/efectos adversos , Resección Endoscópica de la Mucosa/efectos adversos , Neoplasias Esofágicas/cirugía , Humanos , Estudios Retrospectivos , Factores de Riesgo
14.
Ann Surg Oncol ; 27(11): 4360-4368, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32356270

RESUMEN

BACKGROUND: RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. METHODS: Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RESULTS: RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. CONCLUSIONS: RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.


Asunto(s)
Proteínas de Unión al ADN , Neoplasias Gástricas , Ubiquitina-Proteína Ligasas , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Progresión de la Enfermedad , Humanos , Invasividad Neoplásica , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Ubiquitina-Proteína Ligasas/biosíntesis , Ubiquitina-Proteína Ligasas/genética
15.
Ann Surg Oncol ; 27(3): 933-942, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31571056

RESUMEN

BACKGROUND: We investigated whether the expression of transforming growth factor-beta-induced protein (TGFBI) and intratumoral immune cells including CD8- and Forkhead box protein P3 (Foxp3)-positive T cells in clinical lung cancer patients could predict the therapeutic response to nivolumab. METHODS: Thirty-three patients who were treated with nivolumab were enrolled in this study. Immunohistochemical analyses of TGFBI, PD-L1, CD8, Foxp3, and vimentin expression were conducted. Serum concentrations of TGFBI and transforming growth factor-beta1 (TGF-ß1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cancer TGFBI was not associated with prognosis and therapeutic response to nivolumab, but cancer stromal TGFBI and intratumoral CD8-positive T cells were associated with them. Therefore, we evaluated cancer stromal TGFBI and intratumoral CD8-positive T cells. The high-TGFBI-expression group had poorer clinical responses than did the low-TGFBI-expression group (p < 0.0001). The number of times nivolumab was administered in the high-CD8-expression group was significantly higher than that in the low-CD8-expression group (p = 0.0046). The high-CD8-expression group had better clinical responses than did the low-CD8-expression group (p = 0.0013). Interestingly, all patients in the high-TGFBI/low-CD8-expression group had progressive disease (PD). In contrast, all patients in the low-TGFBI/high-CD8-expression group had PR + SD (partial response + stable disease) by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CONCLUSIONS: The dual evaluation of stromal TGFBI and intratumoral CD8-positive T cells could be a useful predictive marker for nivolumab.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Antineoplásicos Inmunológicos/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Células del Estroma/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/metabolismo , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Masculino , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Factor de Crecimiento Transformador beta1/genética
17.
BMC Cancer ; 18(1): 597, 2018 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-29801468

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC. METHODS: The expression of FOXC2 and EMT-related markers was evaluated by immunohistochemistry in 84 cases of hepatocellular carcinoma. RESULTS: A high expression of FOXC2 was observed in 26 of 84 cases, and expression was significantly correlated with background liver cirrhosis, poor tumor differentiation, high serum AFP, and elevated cell proliferation markers. In addition, this high expression was related to the induction of the Cadherin switch and vimentin expression and was an independent predictor for poor prognosis. CONCLUSION: The high expression of FOXC2 in HCC is correlated with tumor malignancy and poor prognosis, suggesting that FOXC2 may be an important prognostic factor for HCC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Factores de Transcripción Forkhead/metabolismo , Neoplasias Hepáticas/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Diferenciación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Hígado/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Regulación hacia Arriba
18.
Digestion ; 97(1): 20-25, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29393163

RESUMEN

BACKGROUND: Only limited data are available concerning the long-term outcomes of imatinib treatment among Japanese or Asian patients with advanced or recurrent gastrointestinal stromal tumors (GIST). Our multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent GIST. SUMMARY: The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001 to 2011 were retrospectively reviewed (GREAT study). Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3, 74.9, and 53.8% respectively. In univariate and multivariate analyses, imatinib continuation with dose reduction and achieving a complete or partial response were found to be associated with increased OS. The results of 2 large-scale, long-term trials demonstrate that the risk of tumor progression decreases with increased treatment duration. Furthermore, the interruption of imatinib treatment in responsive and controlled patients results in a high risk of disease progression. Key Messages: Long-term imatinib treatment is recommended for patients with nonprogressive disease. If patients experience significant toxicities, temporary dose reduction and treatment continuation might be useful.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/terapia , Mesilato de Imatinib/uso terapéutico , Recurrencia Local de Neoplasia/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/sangre , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Gastrectomía , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/sangre , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib/sangre , Japón/epidemiología , Cuidados a Largo Plazo/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Inhibidores de Proteínas Quinasas/sangre , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
20.
Surg Case Rep ; 9(1): 9, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36689043

RESUMEN

BACKGROUND: Ischemic colitis affects the left colon in elderly individuals and localization on the right side, especially in the cecum, is rare. We report a case of gangrenous ischemic colitis localized in the cecum of a patient undergoing hemodialysis. CASE PRESENTATION: A 73-year-old man had been undergoing hemodialysis for chronic renal failure caused by diabetic nephropathy. He experienced frequent vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography revealed thickening of the cecal wall, poor enhancement, dilation of the cecum, and intrahepatic portal emphysema. No obvious abnormal findings were observed in the appendix. The patient was diagnosed with cecal necrosis and ileocecal resection was performed. Histopathological examination revealed gangrenous ischemic colitis of the cecum. He was discharged 12 days after surgery without postoperative complications. CONCLUSION: It is important to consider the possibility of ischemic colitis of the right colon in the event of renal failure requiring dialysis, to ensure that opportunities for surgical intervention are not missed.

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