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1.
BMC Cancer ; 24(1): 252, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395832

RESUMEN

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).


Asunto(s)
Niacinamida/análogos & derivados , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Irinotecán , Neoplasias Gástricas/patología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Antígeno B7-H1 , Camptotecina , Estudios Retrospectivos , Neoplasias Peritoneales/tratamiento farmacológico , Fluorouracilo , Leucovorina , República de Corea/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
2.
Cancer Res Treat ; 55(4): 1250-1260, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37232070

RESUMEN

PURPOSE: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. MATERIALS AND METHODS: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. RESULTS: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. CONCLUSION: Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.


Asunto(s)
Neoplasias Gástricas , Anciano , Humanos , Capecitabina , Neoplasias Gástricas/patología , Oxaliplatino/efectos adversos , Cisplatino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Fluorouracilo/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Chaperonas Moleculares/uso terapéutico , Proteínas Supresoras de Tumor
3.
Asian J Surg ; 45(1): 448-455, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34364765

RESUMEN

PURPOSE: 45% of colon cancer patients are elderly, yet they are often deviated from standard cancer management. The MOSAIC trial favored FOLFOX over FL with superior oncologic outcomes; however, which regimen is most beneficial in elderly population remains unclear. This study aimed to compare the efficacy of oxaliplatin-added chemotherapy and capecitabine monotherapy in high-risk stage II/stage III elderly colon cancer patients. METHODS: Colon cancer patients ≥70 years of age who received adjuvant chemotherapy at Inje University Busan Paik Hospital between February 2009 to April 2016 were included. Patients were separated into the oxaliplatin-added group and capecitabine monotherapy group. The primary outcomes were CSS and OS. RESULTS: Of 74 patients, 45 received oxaliplatin-added chemotherapy and 29 received capecitabine monotherapy. There was no difference between the two groups in CSS or OS (p = 0.9670 and p = 0.6801, respectively). The N stage was significantly associated with CSS in both uni/multivariate analysis (p = 0.0565 and p = 0.0347, respectively). The oxaliplatin-added group had more stage III patients, so we performed a subgroup analysis of CSS and OS based on stage, which also showed no significant difference. CONCLUSIONS: Capecitabine monotherapy is an oncologically safe regimen compared to oxaliplatin-added regimens in elderly patients with high-risk stage II/stage III colon cancer.


Asunto(s)
Neoplasias del Colon , Fluorouracilo , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Fluorouracilo/uso terapéutico , Humanos , Estadificación de Neoplasias , Oxaliplatino/uso terapéutico
4.
Cancer Res Treat ; 52(1): 277-283, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31319640

RESUMEN

PURPOSE: The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage. MATERIALS AND METHODS: Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. RESULTS: Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. CONCLUSION: Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.


Asunto(s)
Adenocarcinoma de Células Claras/diagnóstico , Neoplasias Ováricas/diagnóstico , Adenocarcinoma de Células Claras/etiología , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/etiología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Pronóstico , República de Corea , Estudios Retrospectivos , Resultado del Tratamiento
5.
J Geriatr Oncol ; 10(5): 733-741, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30765268

RESUMEN

BACKGROUND: Studies of older patients with colorectal cancer(CRC) have found inconsistent results about the correlation of various comorbidities with overall survival(OS) and treatment tolerance. To refine our understanding, we evaluated this correlation using the Cumulative Illness Rating Scale-Geriatric(CIRS-G) and heat maps to identify subgroups with the highest impact. METHODS: We retrospectively reviewed 153 patients aged 65 years and older with stage IV CRC undergoing chemotherapy. We calculated CIRS-G scores, and a Total Risk Score(TRS) derived from a previous heat map study. The association between CIRS-G scores/TRS and OS, unplanned hospitalizations, and chemotoxicity was examined by the Cox proportional hazards model. RESULTS: Median age was 71 years. Median MAX2 score of chemotherapies was 0.134(0.025-0.231). The most common comorbidities were vascular(79.8%), eye/ear/nose/throat(68%), and respiratory disease(52.4%). Median OS was 25.1 months(95% confidence interval: 21.2-27.6). In univariate analysis, ECOG PS ≥ 2(HR 1.86(1.1-3.17), p = 0.019), poorly differentiated histology(HR 2.03(1.27-3.25), p = 0.003), primary site(rectum vs colon)(HR 0.58 (0.34-0.98), p = 0.04), age at diagnosis(HR per 5y 1.20 (1.04-1.39), p = 0.012), and number of CIRS-G grade 4 comorbidities(HR 1.86 (1.1-3.17), p = 0.019) were associated with OS. In multivariate analysis, the number of CIRS-G grade 4 comorbidities lost significance, although it retained it in the subgroup of patients with colon cancer. Conversely, the TRS was associated with OS in patients with rectal cancer. No association of comorbidity with unplanned hospitalization or chemotoxicity was observed. CONCLUSIONS: In older adults with metastatic CRC, the number of CIRS-G grade 4 comorbidities was associated with worse OS but no specific CIRS-G category was independently associated with OS, unplanned hospitalization, or toxicities.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Afecciones Crónicas Múltiples/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Comorbilidad , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/secundario , Masculino , Metástasis de la Neoplasia , Enfermedades Otorrinolaringológicas/epidemiología , Modelos de Riesgos Proporcionales , Enfermedades Respiratorias/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia
6.
Cancer Res Treat ; 51(1): 1-11, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29397659

RESUMEN

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Tegafur/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante/efectos adversos , Cisplatino/efectos adversos , Docetaxel/efectos adversos , Docetaxel/uso terapéutico , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , República de Corea , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Tegafur/efectos adversos , Resultado del Tratamiento
7.
Immune Netw ; 18(4): e26, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30181914

RESUMEN

Thapsigargin (TGN) is a potent and selective inhibitor of sarco-endoplasmic Ca2+-ATPase, leading to rapid elevation of cytoplasmic Ca2+ concentration. Previous reports have shown that TGN increases the production of various cytokines from macrophages and dendritic cells. Here, we examine the effects of TGN on murine T cells. Nanomolar concentrations of TGN are a significant inducer of IL-2 production with full activity at 50 nM. Micromolar concentrations of TGN, however, are inhibitory to IL-2 production and T cell proliferation. The IL-2 production-inducing activity of TGN is much more prominent when T cells are primed with concanavalin A or anti-CD3 mAb, and is due to the increase of cytoplasmic Ca2+ concentration. TGN at 50 nM does not affect interferon-gamma or IL-4 production from T cells. Thus, the present study shows that low nanomolar concentrations of TGN could be useful in potentiating IL-2 production from antigen-primed T cells.

8.
Oncoimmunology ; 7(5): e1421890, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29721370

RESUMEN

Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer. The anti-neu antibody inhibited tumor growth and enhanced anti-tumor immunity in HER2/neu+ breast cancer TUBO models, whereas GDC-0941 or A66 alone did not. Anti-neu antibody and PI3K inhibitor synergistically promoted anti-tumor immunity by increasing functional T cell production. In the presence of the anti-neu antibody, A66 was more effective than GDC-0941 at increasing the fraction of CD4+, CD8+, and IFN-γ+CD8+ T cells in the tumor-infiltrating lymphocyte population. Detection of IFN-γ levels by enzyme-linked immunospot assay showed that the numbers of tumor-specific T cells against neu and non-neu tumor antigens were increased by combined PI3K inhibitor plus anti-neu antibody treatment, with A66 exhibiting more potent effects than GDC-0941. In a TUBO (neu+) and TUBO-P2J (neu-) mixed tumor model representing immunohistochemistry 2+ tumors, A66 suppressed tumor growth and prolonged survival to a greater extent than GDC-0941 when combined with anti-neu antibody. These results demonstrate that a PI3K p110α-isoform-selective inhibitor is an effective adjunct to trastuzumab in the treatment of HER2-positive breast cancer.

9.
Gastric Cancer ; 21(5): 819-830, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29427038

RESUMEN

BACKGROUND: Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP). METHODS: Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen. RESULTS: Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS. CONCLUSION: In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Pronóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Resultado del Tratamiento , Ramucirumab
10.
Korean J Intern Med ; 33(2): 383-390, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-27048257

RESUMEN

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.


Asunto(s)
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Vejiga Urinaria , Adenocarcinoma/diagnóstico por imagen , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Cuidados Paliativos , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto Joven
12.
Contemp Clin Trials Commun ; 8: 55-61, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29696197

RESUMEN

INTRODUCTION: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. METHODS: This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. DISCUSSION: We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

13.
Int J Oncol ; 50(1): 185-192, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27922686

RESUMEN

A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent. We observed that the effect of NecroX-5 correlated with a reduction in mitochondrial ROS, but mitochondrial ROS reduction by MitoQ did not inhibit cell migration. NecroX-5 decreased intracellular calcium concentration by blocking Ca2+ influx, which mediated the inhibition of cell migration, AKT downregulation and the reduction of mitochondrial ROS levels. However, the reduction of mitochondrial ROS was not associated with supressed migration and AKT downregulation. Our study demonstrates the potential of NecroX-5 as an inhibitor of breast cancer metastasis.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Proteína Oncogénica v-akt/biosíntesis , Sulfonas/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Calcio/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Metástasis de la Neoplasia , Proteína Oncogénica v-akt/genética , Compuestos Organofosforados/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/administración & dosificación , Ubiquinona/análogos & derivados , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Blood Res ; 51(3): 187-192, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27722130

RESUMEN

BACKGROUND: This study aimed to assess the treatment outcomes of ifosphamide, mesna, etoposide, and prednisolone (IMEP) combination regimen as a front-line chemotherapy in patients with peripheral T-cell lymphomas (PTCLs). METHODS: Clinical data of 38 newly diagnosed PTCLs patients who underwent IMEP at Busan Paik Hospital from January 2002 to December 2013 were retrospectively analyzed. RESULTS: The overall response rate was 68.5%, with 21 (55.3%) complete response/complete response unconfirmed and 6 (15.8%) partial response (PR). The median follow-up duration was 25.5 months (range, 0.2-87.3). The median overall survival was not reached and 2-year survival rate was 67%. The median progression free survival was 23 months. The most frequently reported adverse effects higher than grade 3 were hematologic toxicities including neutropenia (68.4%), thrombocytopenia (42.1%). There was no treatment-related mortality. CONCLUSION: IMEP regimen is effective and safe as a front-line chemotherapy in patients with PTCLs.

15.
J Cancer ; 7(9): 1174-80, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27326262

RESUMEN

PURPOSE: We performed this study to analyze the clinical features and prognosis of Korean patients with liposarcoma. PATIENTS & METHODS: Between October 1986 and April 2013, 231 patients who were diagnosed with liposarcoma by histologic examination were enrolled in this study. RESULTS: The distribution of histologic subtypes was well-differentiated (n = 97, 42%), myxoid (n = 74, 32%), dedifferentiated (n = 32, 13.9%), pleomorphic (n = 15, 6.5%), and round-cell liposarcoma (n = 13, 5.6%). The majority of liposarcomas were located in the lower extremities (35.5%) and retroperitoneum (34.2%). Prognosis was worse for the trunk group compared with the extremity group (median disease-free survival [DFS] 3.3 vs. 9.9 years, respectively, P <0.001). Median DFS was significantly worse in patients with high grade histology compared to those with low grade histology (16.9% vs. 65.7%, P <0.001). The independent prognostic factors associated with survival were histology (hazard ratio [HR] 3.01; 95% confidence interval [CI], 1.82-4.97; P <0.001) and primary site (HR 1.80; 95% CI, 1.12-2.89; P = 0.015). Three risk groups with different survival outcomes were identified: group 1 (n = 98), no risk factors; group 2 (n = 92), one risk factor; and group 3 (n = 41), two risk factors. CONCLUSIONS: Histologic subtype and primary site were independent prognostic factors for curatively resected liposarcoma. A prognostic model for patients with liposarcoma clarified distinct groups of patients with good prognostic discrimination.

16.
Oncotarget ; 7(17): 24549-58, 2016 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-27016421

RESUMEN

BACKGROUND: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. PATIENTS AND METHODS: A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). RESULTS: Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. CONCLUSIONS: We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Amplificación de Genes , Liposarcoma/genética , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Liposarcoma/diagnóstico , Liposarcoma/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Adulto Joven
18.
Cancer Res Treat ; 48(4): 1286-1292, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26875195

RESUMEN

PURPOSE: We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. MATERIALS AND METHODS: Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment. RESULTS: Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m2. The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. CONCLUSION: Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Everolimus/efectos adversos , Insuficiencia Renal/tratamiento farmacológico , Sirolimus/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Insuficiencia Renal/complicaciones , Insuficiencia Renal/patología , Sirolimus/efectos adversos , Sirolimus/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Resultado del Tratamiento
19.
Case Rep Oncol ; 8(3): 456-60, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26600779

RESUMEN

A subphrenic mass was noted on a surveillance computed tomography (CT) scan of a 65-year-old man who had achieved complete remission of oropharyngeal cancer after concurrent chemoradiotherapy. The mass was 3.2 cm in size and showed a multilobular enhancing pattern along the peritoneal lining. The patient was negative for hepatitis B surface antigen and anti-hepatitis C virus antibody. His carcinoembryonic antigen level was within the normal range. Contrast-enhanced CT revealed no mass in the liver. He underwent surgery, and a pale yellowish soft tumor measuring 3.8 × 3.2 × 1.2 cm was resected. Histologically, the tumor was confirmed to be a hepatocellular carcinoma. Currently, he is doing well, and has been followed up without any signs of recurrence.

20.
Case Rep Oncol ; 8(2): 246-50, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26120309

RESUMEN

Primary peritoneal carcinoma (PPC) is a rare cancer arising from the extraovarian peritoneum and is of müllerian origin. PPC and epithelial ovarian carcinoma share similar clinical, histopathological, and immunohistochemical features. Clinical symptoms and findings include abdominal distension and ascites. We experienced 2 cases of PPC which initially presented with cervical lymphadenopathy. Here, we report the 2 cases and review the literature.

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