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1.
Anticancer Res ; 39(10): 5581-5588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570453

RESUMO

BACKGROUND/AIM: The utility of peripheral blood neutrophil-to-lymphocyte ratios (NLRs) and platelet-to-lymphocyte ratios (PLRs) as prognostic predictors of surgery and chemotherapy in breast cancer has been reported. In this study, NLRs and PLRs were calculated before treatment and during cancer progression in primary hormone receptor-positive breast cancer (HRBC) patients who chose endocrine therapy (ET) as the primary treatment, and prognostic prediction and factor analysis were performed. PATIENTS AND METHODS: A total of 55 patients diagnosed with stage IIIB, IIIC, or IV HRBC who received ET as the primary treatment were included. RESULTS: Increased NLRs were found to significantly contribute to a shorter overall survival from cancer progression (OS-CP) (p=0.040, log-rank). Increased PLRs were similarly associated with a shorter OS-CP (p=0.036, log-rank). In multivariate analysis, an increased NLR was an independent prognostic factor (p=0.035, hazard ratio(HR)=5.221). CONCLUSION: Changes in NLRs and PLRs become prognostic indicators when the therapeutic effect of ET is limited.


Assuntos
Plaquetas/patologia , Neoplasias da Mama/patologia , Células Endócrinas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Prognóstico , Estudos Retrospectivos
2.
Anticancer Res ; 39(9): 5039-5045, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519612

RESUMO

BACKGROUND/AIM: Although complete resection of liver metastases colorectal cancer (CLM) is the only potentially curative treatment, surgery alone is not enough, as the recurrence rate after resection is high. Therefore, in clinical practice, adjuvant chemotherapy is performed after resection of CLM. However, the evidence supporting the efficacy of such adjuvant chemotherapy is not sufficient. Previous reports have noted that adjuvant chemotherapy after resection of CLM is effective only in patients with a high risk of recurrence. The purpose of this study was to classify the risk of recurrence using systemic inflammatory markers reportedly associated with clinical outcomes in patients with various types of malignancies, and evaluate the efficacy of adjuvant chemotherapy according to the risk of recurrence. PATIENTS AND METHODS: The medical records of 119 patients with CLM who underwent potentially curative surgery between 1996 and 2017 were retrospectively reviewed. Preoperative blood samples were obtained within 2 weeks before resection of CLM. was calculated from the blood samples Dividing the serum C-reactive protein level by the serum albumin level derived the C-reactive protein-to-albumin ratio (CAR), reflecting the risk of recurrence. The optimal cut-off value of the CAR was determined according to receiver operating characteristic curve analysis, and then the patients were classified into the high-CAR (high recurrence risk) or low-CAR (low recurrence risk) group. The relationship between the CAR and relapse-free survival after resection of CLM was examined and the efficacy of adjuvant chemotherapy according to the risk of recurrence was evaluated. RESULTS: The cut-off value of the CAR was set at 0.0471. The relapse-free survival rate was significantly better in the low-CAR group than in the high-CAR group. Efficacy of adjuvant chemotherapy after resection of CLM was not recognized in the low-CAR group, whereas the relapse-free survival rates were significantly better for patients who were treated with adjuvant chemotherapy after resection of CLM in the high-CAR group. CONCLUSION: The preoperative CAR, as a systemic inflammatory marker, was found to be useful as a prognostic marker in patients with CLM who were treated with potentially curative resection. Furthermore, it was suggested that adjuvant chemotherapy after resection of CLM may be effective for preventing recurrence in patients with high levels of inflammatory markers who have a high risk of recurrence.


Assuntos
Biomarcadores , Neoplasias Colorretais/patologia , Mediadores da Inflamação/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Recidiva , Estudos Retrospectivos , Adulto Jovem
3.
Anticancer Res ; 39(9): 5157-5163, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519628

RESUMO

BACKGROUND/AIM: Neoadjuvant therapy is often administered to patients with locally advanced rectal cancer (LARC). The aim of this study was to investigate the correlation between the change in the psoas muscle index (PMI) during neoadjuvant therapy and the prognosis of LARC patients. PATIENTS AND METHODS: Forty-seven patients who underwent potentially curative surgery for LARC with neoadjuvant therapy were enrolled in this study. We evaluated the relationship between the prognosis and clinicopathological factors, including the prognostic value of a change in the PMI. RESULTS: A >10% decrease in the PMI value was observed in 15 of the 47 patients. A >10% decrease in the PMI value was associated with shorter OS and RFS compared to patients who did not show a >10% decrease in their PMI. The decrease in PMI after neoadjuvant therapy was an independent negative prognostic factor for patients undergoing neoadjuvant therapy for LARC. CONCLUSION: A decrease in PMI after neoadjuvant therapy might predict a poor prognosis in LARC patients undergoing neoadjuvant therapy.


Assuntos
Músculos Psoas/patologia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tamanho do Órgão , Prognóstico , Curva ROC , Neoplasias Retais/terapia , Resultado do Tratamento , Adulto Jovem
4.
Anticancer Res ; 39(8): 4031-4041, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366485

RESUMO

BACKGROUND/AIM: Eribulin is currently used to treat advanced and metastatic breast cancer in the clinical setting; however, its efficacy is inhibited by resistance acquisition in many cases. Thus, the present study established two eribulin-resistant breast-cancer cell lines, and used these to investigate the mechanisms that underly eribulin-resistance acquisition. MATERIALS AND METHODS: Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin. RESULTS: The eribulin-resistant cells acquired resistance to eribulin, as well as several other anticancer drugs. After eribulin treatment, the eribulin-resistant cell lines showed no morphological change, no increased expression of epithelial-cadherin, nor any significant alteration in cell-cycle distribution. In contrast, the expression levels of programmed death-ligand 1 were increased in the MCF-7/eribulin-resistant compared to MCF-7 cells. CONCLUSION: The herein developed eribulin-resistant cell lines acquired cross-resistance to various anticancer agents, and displayed resistance to eribulin-induced effects on microtubule function and epithelial-mesenchymal transition (EMT).


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Furanos/administração & dosagem , Cetonas/administração & dosagem , Animais , Antineoplásicos/efeitos adversos , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Células MCF-7 , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Gan To Kagaku Ryoho ; 46(5): 895-899, 2019 May.
Artigo em Japonês | MEDLINE | ID: mdl-31189811

RESUMO

The RAINBOW trial showed that paclitaxel(PTX)plus ramucirumab(RAM)therapy improved the survival of patients with advanced gastric cancer, previously treated with chemotherapy. We retrospectively investigated 33 patients with unresectable or recurrent gastric cancer who underwent PTX plus RAM treatment as second- or third-line chemotherapy between September 2015 and December 2017. The median age was 68(45-84)years with 22 patients(67%)aged 65 years or older. Seventeen patients had unresectable and 16 patients had recurrent gastric cancer. ECOG PS was 2 in 5 patients(16%). PTX plus RAM was administered as second-line therapy for 24 patients, and as third-line therapy for 9 patients. Best overall response was partial response(PR)in 4 patients, stable disease(SD)in 14 patients, and progressive disease(PD)in 9 patients. Response rate(RR)and disease control rate(DCR)were 14.8% and 66.7%, respectively. Grade 3/4 adverse events were observed in 28(85%)of(leucopenia·neutropenia[64%], neuropathy[9%], etc). Median follow-up period was 7.3(0.4- 22.4)months. Median OS and PFS were 9.3(0.4-22.4)months and 4.7(0.4-22.4)months, respectively. We conclude that PTX plus RAM therapy is useful for treating unresectable or recurrent gastric cancer. In clinical practice, we have many opportunities to provide PTX plus RAM therapy for patients of older age and poorer PS; careful attention to adverse events is essential in such cases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
6.
Anticancer Res ; 39(6): 2941-2950, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177133

RESUMO

BACKGROUND: Several studies have established a positive relationship between quality of life (QOL) and prognosis in patients with various cancer types. This study investigated QOL of elderly patients with primary hormone receptor-positive breast cancer who chose endocrine therapy as their first-line treatment. PATIENTS AND METHODS: QOL-ACD-B scores were evaluated before and after endocrine therapy for 75 patients. The results of the interviews were used to determine the Charlson Comorbidity Index. RESULTS: In a univariate analysis, baseline objective response rate (p=0.009), and increase in QOL (p=0.037) significantly correlated with longer progression-free survival time. There was a correlation between 3-month QOL score and longer overall survival in the multivariate analysis (p=0.035). CONCLUSION: In elderly patients with breast cancer who underwent first-line endocrine therapy, improved QOL at 3 months after treatment initiation correlated with prolonged progression-free survival. High QOL scores were associated with prolonged overall survival.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Prognóstico , Intervalo Livre de Progressão , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
7.
Anticancer Res ; 39(5): 2259-2264, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092417

RESUMO

Disseminated intravascular coagulation (DIC) that occurs during cancer therapy prevents continuation of therapy, contributing to a worse prognosis. While recombinant human-soluble thrombomodulin (rhTM), a new DIC drug, has occasionally shown its efficacy in DIC associated with infection and blood cancer, its efficacy in patients with solid tumors has been unproven. This review presents the results on the efficacy and safety of rhTM as a DIC drug in patients with solid tumors that have been confirmed by the clinical data of three previous reports. The number of cases in each study was 101, 123 and 40. The respective DIC resolution rate was 34.0%, 35.2% and 32.5%, and the 28-day survival rate was 55.4%, 52.0% and 40.0%. Although comparison with other anti-DIC therapies is required, rhTM therapy is considered one of the treatment options of DIC in patients with solid tumors.


Assuntos
Coagulação Intravascular Disseminada/tratamento farmacológico , Neoplasias/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Trombomodulina/uso terapêutico , Coagulação Intravascular Disseminada/genética , Coagulação Intravascular Disseminada/patologia , Humanos , Neoplasias/genética , Neoplasias/patologia , Proteínas Recombinantes/genética , Trombomodulina/genética , Resultado do Tratamento
8.
BMC Cancer ; 19(1): 241, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885163

RESUMO

BACKGROUND: Growing evidence indicates that inflammation contributes to cancer progression, and several inflammatory markers have been reported to be associated with the clinical outcomes in patients with various types of cancer. Recently, the advanced lung cancer inflammation index (ALI) has been developed as a prognostic marker in patients with lung cancer. The difference between the ALI and the inflammatory markers reported in the previous studies is that the ALI contains not only indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. The aim of this study was to evaluate the prognostic significance of the ALI in patients with unresectable metastatic colorectal cancer. METHODS: We retrospectively reviewed a database of 159 patients who underwent combination chemotherapy for unresectable metastatic colorectal cancer between 2008 and 2016. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated from a blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI × serum albumin concentration/NLR. RESULTS: The overall survival rate was significantly worse in the low-ALI group than in the high-ALI group (p < 0.0001). Furthermore, the ALI was an independent prognostic factor for the overall survival (hazard ratio: 2.773, 95% confidence interval: 1.773-4.335, p < 0.001). CONCLUSIONS: A newly developed prognostic marker, the ALI, was found to be a novel prognostic marker in patients with unresectable metastatic colorectal cancer as well as in patients with lung cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Índice de Massa Corporal , Neoplasias Colorretais/mortalidade , Inflamação/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Estudos Retrospectivos , Albumina Sérica Humana/análise , Índice de Gravidade de Doença , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
Surg Today ; 49(5): 361-368, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30805721

RESUMO

The aim of this review was to analyze the currently available literature on single-incision laparoscopic surgery (SILS) for Crohn's disease (CD) with respect to surgical indications, surgical techniques, feasibility, and possible benefits of SILS for CD. A systematic query of articles published from January 2010 to July 2018 was performed. The studies were assessed for patient's age, gender, body mass index, disease type, SILS procedure, surgical procedure, incision length, operation time, rates of conversion to open surgery, postoperative complications, mortality, length of hospital stay, and rates of reoperation. After an initial review, 11 reports were selected. The surgical techniques and instruments showed wide variation. The mean operation time for SILS tended to be shorter than that for multiport laparoscopic surgery (MLS). The reported rates of conversion to open surgery and postoperative complications were not very different from those reported for MLS. In conclusion, the present review suggests that the SILS technique may be feasible and safe for select patients with CD. However, because we reviewed only a few studies with small sample sizes, prospectively designed trials with a large number of patients are required to clarify the true benefits of SILS for CD.


Assuntos
Doença de Crohn/cirurgia , Laparoscopia/métodos , Adolescente , Adulto , Bases de Dados Bibliográficas , Feminino , Humanos , Masculino , Ferida Cirúrgica , Resultado do Tratamento , Adulto Jovem
10.
Anticancer Res ; 39(2): 1051-1057, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30711994

RESUMO

BACKGROUND/AIM: New drugs for metastatic colorectal cancer (mCRC) have been recently developed for use in later-line chemotherapy and have contributed to further prolongation of the survival of patients. However, in later-line chemotherapy, treatment failure may lead to discontinuation of chemotherapy and the transition to best supportive care. Therefore, a biomarker able to predict the effects of later-line chemotherapy is required. The C-reactive protein-to-albumin ratio (CAR), which is an inflammatory marker, has been reported to correlate with therapeutic outcome in patients with mCRC who underwent first-line chemotherapy. However, the significance of the CAR as a marker for predicting the chemotherapeutic outcome in patients with mCRC treated with later-line chemotherapy is unknown. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 40 patients with mCRC who were treated with trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) as a later-line chemotherapy. The CAR was calculated from the blood samples obtained within 1 week before the initiation of FTD/TPI by dividing the serum C-reactive protein level by the serum albumin level. RESULTS: According to the receiver operating characteristic curve analysis, we set 0.122 as the CAR cut-off, and patients were classified into groups with high or low CAR. The low-CAR group had a significantly higher disease control rate than the high-CAR group. The progression-free and overall survival rates were significantly better in the low-CAR group than in the high-CAR group. A high-CAR was associated with a greater number of prior regimens, higher serum lactate dehydrogenase level and more organs with metastases, considered to be correlated with the rate of disease progression. However, no significant differences were observed in the incidence of grade 3 or more adverse events, the relative dose intensity, or the rate of discontinuing chemotherapy between the two groups. CONCLUSION: The CAR may be a useful indicator for predicting the chemotherapeutic outcome in patients with mCRC treated with FTD/TPI as a late-line chemotherapy. The correlation between a high-CAR and poor prognosis was presumed to be due to the rate of cancer growth and increased resistance to chemotherapy rather than an insufficient dose of the drug.


Assuntos
Albuminas/análise , Antineoplásicos/uso terapêutico , Proteína C-Reativa/análise , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Trifluridina/uso terapêutico , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Inflamação , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Timidina Fosforilase/antagonistas & inibidores , Resultado do Tratamento
11.
Anticancer Res ; 38(12): 6721-6727, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30504382

RESUMO

BACKGROUND: The density of tumor-infiltrating lymphocytes has been reported to reflect the antitumor immune status, and many reports have shown that tumor-infiltrating CD8+ and total T-lymphocytes may be strong prognostic biomarkers in colorectal cancer. We previously reported that the density of tumor-infiltrating immune cells in hematoxylin and eosin (H&E)-stained sections may be an easily available prognostic biomarker. However, it remains unclear whether the density of tumor-infiltrating immune cells in H&E-stained sections accurately reflects the antitumor immune status. PATIENTS AND METHODS: A total of 308 patients who underwent curative resection for stage II/III colorectal cancer were enrolled. The density of both tumor-infiltrating immune cells in H&E-stained sections and tumor-infiltrating lymphocyte subsets was assessed by immunohistochemistry. RESULTS: The density of tumor-infiltrating immune cells in H&E-stained sections was significantly and positively correlated with that of tumor-infiltrating CD4+/CD8+/total T-lymphocytes. CONCLUSION: The density of tumor-infiltrating immune cells in H&E-stained sections may be a reasonable immunological biomarker.

12.
Case Rep Oncol ; 11(2): 461-466, 2018 May-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30057541

RESUMO

As a result of recent major advances in chemotherapy for metastatic colorectal cancer, the prognosis for patients with metastatic colorectal cancer has improved. However, elderly patients often cannot receive intensive therapy. There are still many problems to solve regarding treatment for elderly patients with metastatic colorectal cancer. We herein report a case of complete response of pulmonary metastases from rectal cancer to tegafur-uracil (UFT)/leucovorin (LV) + bevacizumab (Bmab) in an elderly patient. An 80-year-old woman who had undergone curative surgery for rectal cancer 5 years ago was diagnosed with pulmonary metastases. Taking into account her advanced age and low renal function (creatinine clearance: 41.2 mL/min), UFT/LV + Bmab therapy was selected. The patient received UFT (300 mg/m2/day) and LV (75 mg/day) on days 1-5, 8-12, and 15-19 and Bmab (7.5 mg/kg) on day 1. The treatment cycle was repeated every 21 days. Following 17 courses of treatment without adverse events, a complete response was observed. Furthermore, there was no recurrence within 6 months after the final course of therapy. This case indicates that UFT/LV + Bmab is suitable for the treatment of elderly patients with metastatic colorectal cancer.

13.
Anticancer Res ; 38(7): 4193-4197, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970549

RESUMO

BACKGROUND/AIM: A single-arm phase II clinical trial was conducted to evaluate the safety and efficacy of adding bevacizumab to standard capecitabine-based neoadjuvant chemoradiotherapy (CRT) for the treatment of locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Twenty-five patients were enrolled. Patients received capecitabine-based CRT for 5 weeks and 3 days. Bevacizumab was administered every 2 weeks during CRT. Within 6-10 weeks after completion of CRT, surgery was performed. RESULTS: With regard to CRT-related acute toxicities, most of the adverse events were limited to grade 1. A pathological complete response was obtained in four (16%) patients. In total, six patients (24%) developed postoperative complications. Six out of five (83%) patients healed without the need for surgical intervention. CONCLUSION: Although acute toxicity during CRT with bevacizumab was minimal and postoperative complications do not seem to increase, the addition of bevacizumab apparently offers no clinically-significant benefit for patients with LARC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Quimiorradioterapia Adjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos
14.
Oncol Lett ; 16(1): 666-672, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29928454

RESUMO

Inflammation has been widely recognized as a contributor to cancer progression and several inflammatory markers have been reported as associated with the clinical outcomes in patients with various types of cancer. Recently, a novel inflammatory marker, the systemic inflammatory score (SIS), which is based on a combination of the lymphocyte-to-monocyte ratio (LMR) and the serum albumin concentration has been reported as a useful prognostic marker. The aim of the present study was to assess the prognostic value of the SIS in patients with unresectable metastatic colorectal cancer (mCRC). The retrospective cohort study included 160 patients who underwent combination chemotherapy for unresectable mCRC between January 2008 and December 2016. The SIS was used to classify the patients into three groups based on their LMR and the serum albumin concentration. Patients with high-LMR and high serum albumin level were given a score of 0; patients with low-LMR or low serum albumin level were given a score of 1; patients with low-LMR and low serum albumin level were given a score of 2. There were significant differences in the overall survival among the three SIS groups and the SIS was an independent prognostic factor for the overall survival. Although the SIS was significantly associated with the overall survival rate even when using the original cut-off values, the SIS according to the new cut-off values had a more accurate prognostic value. The present study determined that the SIS was a useful biomarker for predicting the survival outcomes in patients with unresectable mCRC, although the optimum cut-off value of the SIS according to the patients' background needs to be examined in further studies.

15.
In Vivo ; 32(3): 611-623, 2018 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29695568

RESUMO

BACKGROUND/AIM: A meta-analysis was conducted to evaluate and compare the short- and long-term outcomes of robot-assisted (RAS) and conventional laparoscopic surgery (LAS) for rectal cancer. MATERIALS AND METHODS: We searched MEDLINE for relevant papers published between 2010 and December 2017 by using specific search terms. We analyzed outcomes over short- and long-term periods. RESULTS: We identified 23 papers reporting results that compared RAS for rectal cancer with LAS. Our meta-analysis included 4,348 patients with rectal cancer; 2,068 had undergone RAS, and 2,280 had undergone LAS. In the short- and long-term period, 27 and 7 outcome variables were examined, respectively. RAS for rectal cancer was significantly associated with a greater operative time and a lower conversion rate to open surgery in the short-term, and results in almost similar outcomes in the long-term, compared to LAS. CONCLUSION: RAS may be an acceptable surgical treatment option compared to LAS for rectal cancer.


Assuntos
Laparoscopia , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos , Perda Sanguínea Cirúrgica , Quimiorradioterapia/métodos , Ensaios Clínicos como Assunto , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Terapia Neoadjuvante , Duração da Cirurgia , Complicações Pós-Operatórias , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
16.
Oncotarget ; 9(20): 15180-15197, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29632635

RESUMO

Background: The density of tumor-infiltrating lymphocytes (TILs) have been reported to reflect antitumor immune response and correlate with prognosis in malignancy. However, the methodology for evaluating the density of TILs by an immunohistochemical analysis differs among reports. The aim of this study was to verify the methodology for evaluating the density of TILs by immunohistochemical analysis and thereby identify the optimum methodology in clinical setting. Methods: Three-hundred-thirteen patients who underwent curative operation for stage II/III colorectal cancer were enrolled. We retrospectively examined the density of TILs using immunohistochemical staining according to each method as follows: 1) subset of lymphocytes (i.e. CD4+/CD8+), 2) selected fields (i.e. at random or focusing on hot spots), 3) location in low-power field (i.e. the invasive margin [TILsIM] or the center of the tumor [TILsCT] or the surface of the tumor [TILsST]), and 4) location in high-power field (i.e. in tumor stroma [sTILs] or intra-tumor cells [iTILs] or total TILs [tTILs: sTILs+iTILs]). We then assessed the prognostic value of the density of TILsIM evaluated as described above. We also evaluated the correlation between the density of TILsIM and that of TILsCT/TILsST. Results: Only the densities of CD8+sTILsIM and CD8+tTILsIM evaluated in randomly selected fields were significantly associated with the survival. Furthermore, the density of CD8+TILsIM was significantly associated with that of CD8+TILsCT and CD8+TILsST. Conclusions: We concluded that best and easiest way to evaluate the density of TILs in the clinical setting may be to assess the density of CD8+tTILsIM in randomly selected fields.

17.
BMC Cancer ; 18(1): 371, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29614981

RESUMO

BACKGROUND: The anticancer immune response has been reported to correlate with cancer progression. Tumor-infiltrating lymphocytes (TILs), which are one of the indicators of host immunity, affect the tumor growth, metastasis and chemoresistance. Both TILs in the primary tumor and those in the metastatic tumor have been reported to be a useful predictor of the survival and therapeutic outcome. However, the correlation between the density of TILs in the primary and metastatic tumor is unclear. The aim of this study was to elucidate the correlation between the density of TILs in the primary and metastatic tumor. METHODS: A total of 24 patients with stage IV colorectal cancer who underwent concurrent resection of the primary tumor and liver metastasis were enrolled in order to assess the correlation between the density of TILs in the primary tumor and that in the metastatic tumor. Hematoxylin and eosin (HE)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by the measurement of the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. In addition, to evaluate TIL subsets and the activation/suppression status of the lymphocytes, immunohistochemistry for CD4, CD8, Forkhead boxprotein P3 (FOXP3), programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), inducible T-cell co-stimulator (ICOS), Glucocorticoid induced tumor necrosis factor receptor related protein (GITR), Human Leukocyte Antigen - antigen D Related (HLA-DR) and Granzyme B was performed, and the number of immunoreactive lymphocytes was counted. RESULTS: According to the evaluation using the HE-stained sections, the density of tumor-infiltrating mononuclear inflammatory cells in the primary tumor was significantly associated with that in the metastatic tumor. In addition, according to the immunohistochemistry evaluation, the density of CD4+, CD8+ and FOXP3+ TILs in the primary tumor and that in the metastatic tumor were significantly correlated with that in the metastatic tumor. Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B and the PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor. CONCLUSIONS: The local immune status of the primary tumor was revealed to be similar to that of the metastatic tumor. This suggests that the evaluation of the local immunity of the primary tumor may be a substitute for the evaluation of the local immunity of the metastatic lesion. Therefore, information on the primary tumor may be useful when considering treatment strategies for metastatic lesions.

18.
PLoS One ; 13(4): e0192744, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29698402

RESUMO

PURPOSE: Numerous reports indicate that tumor-infiltrating lymphocytes (TILs) are a prognostic factor in various cancers and that they must be good biomarkers. However, the methods of evaluating TILs differ in each study; thus, there is not yet a standardized methodology for evaluating TILs. The purpose of this study is to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with colorectal cancer (CRC) using the new method proposed by the International TILs Working Group in breast cancer and to standardize the method of evaluating TILs in CRC. METHODS: We retrospectively reviewed a database of 160 patients with Stage II or III CRC. The density of TILs was assessed by measuring the area occupied by mononuclear cells over the stromal area on hematoxylin and eosin (H-E)-stained sections. We set 42% as the cut-off percentage of the area occupied by TILs according to the receiver operating characteristic curve, and we classified patients into the high-TILs and the low-TILs groups. RESULTS: The rates of relapse-free survival (RFS) and overall survival (OS) in the high-TILs group were significantly higher than those in the low-TILs group. A multivariate analysis showed that the density of TILs was independently associated with RFS and OS. Moreover, the density of TILs assessed by an observer was significantly associated with the density of TILs assessed by the automated imaging software program. CONCLUSIONS: The new method for evaluating TILs, which was recommended by the International TILs Working Group in breast cancer, might be a useful predictive factor in colorectal cancer patients.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral/patologia , Coloração e Rotulagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amarelo de Eosina-(YS) , Feminino , Corantes Fluorescentes , Hematoxilina , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Anticancer Res ; 38(4): 2031-2035, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29599320

RESUMO

BACKGROUND: miR-96 is reported to inhibit reversion cysteine-rich Kazal motif (RECK), which is associated with tumor invasion, in solid cancer types (e.g. breast cancer, non-small cell lung cancer, esophageal cancer). The purpose of this study is to clarify whether miR-96 is similarly associated with tumor invasion in colorectal cancer. MATERIALS AND METHODS: We performed western blotting to investigate the expression of RECK when miR-96 mimics or inhibitors were transferred into HCT-116 colorectal cancer cells. The RECK mRNA level was assessed by a reverse transcription polymerase chain reaction. An invasion assay was used to evaluate tumor invasion. RESULTS: The expression of RECK was inhibited by the transfection of miR-96 mimics. RECK mRNA level was reduced by miR-96 mimics and increased by miR-96 inhibitor. In the invasion assay, miR-96 mimics were shown to promote tumor invasion. CONCLUSION: miR-96 may be associated with tumor invasion through inhibition of RECK expression in colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Ligadas por GPI/antagonistas & inibidores , MicroRNAs/genética , Materiais Biomiméticos/administração & dosagem , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Células HCT116 , Humanos , MicroRNAs/administração & dosagem , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção , Regulação para Cima
20.
Cancer Sci ; 109(4): 966-979, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29464828

RESUMO

Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty-four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post-treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post-treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post-treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte-mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Neoplasias Retais/imunologia , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Linfócitos T CD8-Positivos/imunologia , Quimiorradioterapia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia
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