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1.
BMC Cancer ; 19(1): 988, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647032

RESUMO

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

2.
J Thorac Dis ; 11(3): 777-787, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31019765

RESUMO

Background: The expression of CCL28 and its relationship with clinical outcomes remain unclear in the setting of heterogeneous breast cancer. The purpose of the current study was to identify the expression characteristics of chemokine CCL28 in breast cancer, with a focus on its prognostic relevance to different subtypes. Methods: First, we investigated the expression of CCL28 in 150 breast cancer patients immunohistochemically and assessed the impact of CCL28 on relapse-free survival (RFS) in the whole cohort and different clinical subtypes [defined by hormone receptor (HR), and HER-2 status] by univariate and multivariate analysis. Furthermore, the other two cohorts comprised of 863 patients from the Cancer Genome Atlas (TCGA) database and 1,764 patients from the Kaplan-Meier plotter database, respectively, were chosen to validate the prognostic values of CCL28 in breast cancer. Results: Those with positive CCL28 expression had improved RFS in luminal-like (HR positive, any HER-2 status) subtype (P=0.052) but had impaired RFS in triple-negative cases (P=0.019), after adjustment with tumor size and lymph node status. Consistently, multivariate analysis in the TCGA cohort revealed improved disease-free survival (DFS) among patients with high expression of CCL28 in luminal-like subtype (P=0.043) and decreased DFS in patients expressing high CCL28 in triple-negative cases (P=0.010). The subsequent analysis of the Kaplan-Meier plotter cohort also demonstrated that CCL28 was a favorable prognostic factor for luminal-like cases [luminal A (P<0.001) and luminal B (P=0.031)], but a poor prognostic indicator for the patients with triple-negative phenotype (P<0.001). Conclusions: CCL28 was a favorable prognostic factor for luminal-like cases and detrimental for triple-negative subtype, indicating that the same chemokine may play different or even opposite roles in the recurrence and metastasis of different molecular subtypes of breast cancer.

3.
J Biomed Inform ; 86: 1-14, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30103028

RESUMO

BACKGROUND AND OBJECTIVE: Clinical prognosis prediction plays an important role in clinical research and practice. The construction of prediction models based on electronic health record data has recently become a research focus. Due to the lack of external validation, prediction models based on single-center, hospital-specific datasets may not perform well with datasets from other medical institutions. Therefore, research investigating prognosis prediction model construction based on a collaborative analysis of multi-center electronic health record data could increase the number and coverage of patients used for model training, enrich patient prognostic features and ultimately improve the accuracy and generalization of prognosis prediction. MATERIALS AND METHODS: A web service for individual prognosis prediction based on multi-center clinical data collaboration without patient-level data sharing (POPCORN) was proposed. POPCORN focuses on solving key issues in multi-center collaborative research based on electronic health record systems; these issues include the standardization of clinical data expression, the preservation of patient privacy during model training and the effect of case mix variance on the prediction model construction and application. POPCORN is based on a multivariable meta-analysis and a Bayesian framework and can construct suitable prediction models for multiple clinical scenarios that can effectively adapt to complex clinical application environments. RESULTS: POPCORN was validated using a joint, multi-center collaborative research network between China and the United States with patients diagnosed with colorectal cancer. The performance of the models based on POPCORN was comparable to that of the standard prognosis prediction model; however, POPCORN did not expose raw patient data. The prediction models had similar AUC, but the BMA model had the lowest ECI across all prediction models, indicating that this model had better calibration performance than the other models, especially for patients in Chinese hospitals. CONCLUSIONS: The POPCORN system can build prediction models that perform well in complex clinical application scenarios and can provide effective decision support for individual patient prognostic predictions.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Sistemas de Apoio a Decisões Clínicas , Registros Eletrônicos de Saúde , Internet , Acesso à Informação , Idoso , Algoritmos , Teorema de Bayes , Calibragem , China , Diagnóstico por Computador , Feminino , Humanos , Disseminação de Informação , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Reprodutibilidade dos Testes , Estados Unidos
4.
Oncol Lett ; 15(1): 1184-1190, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29399173

RESUMO

Increasing evidence demonstrates that microRNAs (miRNAs/miRs), a type of non-coding small RNA, can regulate tumor cell migration, invasion and metastasis, and may therefore serve a major function in the occurrence and development of tumors. The present study investigated the effect of miR-383 on the proliferation, migration and invasion of colon cancer HT-29 and LoVo cell lines. The expression of miR-383 in colon cancer and adjacent non-tumor tissues was examined by reverse transcription-quantitative polymerase chain reaction. MiR-383 upregulation was stimulated by transfection with a miR-383 mimic. Cell proliferation was measured with MTT and colony formation assays, and cell migration and invasion potential were examined by Transwell chamber assays. A proliferating-inducing ligand (APRIL), myeloid cell leukemia-1 and cyclooxygenase-2 protein expression was analyzed by western blotting. The expression of miR-383 was decreased in colon cancer tissues compared with adjacent non-tumor tissues (P<0.05). Transfection with a miR-383 mimic suppressed proliferation and inhibited cell migration and invasion in HT-29 and LoVo colon cancer cell lines. Overexpression of miR-383 in HT-29 and LoVo cells resulted in the suppression of APRIL protein expression. In conclusion, miR-383 was downregulated in colon cancer. The upregulation of miR-383 inhibited proliferation, migration and invasion of colon cancer cells, potentially through the regulation of target gene APRIL.

5.
Chin J Cancer ; 36(1): 97, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29273089

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. METHODS: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. RESULTS: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3-4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). CONCLUSION: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Indóis/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirróis/administração & dosagem , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Indóis/efeitos adversos , Masculino , Metástase Neoplásica , Inibidores de Proteínas Quinases/efeitos adversos , Pirróis/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
6.
Oncotarget ; 8(45): 79618-79628, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108341

RESUMO

Objective: The role of surgery in metastatic colorectal cancer (mCRC) remains controversial. This study was performed to assess the impact of surgery on survival in metastatic colorectal cancer. Materials and Methods: Information of mCRC patients diagnosed between January 1, 2004, and December 31, 2013, was retrieved from the Surveillance, Epidemiology, and End Results Program database. Patients were classified in three groups: patients undergoing resection of both primary and distant metastatic tumors (group 'PMTR'), patients receiving primary tumor resection alone (group 'PTR') and patients not undergoing any surgery (group 'No resection'). Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were applied to estimate disease specific survival time (DSS) and determine prognostic factors. Results: A total of 38,591 mCRC patients were eligible. Overall, median DSS of group 'PMTR' was significantly longer compared with group 'PTR' and group 'No resection' (28.0 vs 21.0 vs 11.0 months, P < 0.001). Stratified analysis observed that primary tumor in left-sided colorectal cancer (LCRC) was a favorable prognostic factor compared with right-sided colorectal cancer (RCRC) (median DSS of LCRC: PMTR, 34 months, PTR, 25 months, No resection, 13 months; median DSS of RCRC: PMTR, 20 months, PTR, 16 months, No resection, 8 months; P < 0.001). Multivariate analysis demonstrated that surgery was an independent prognostic factor for better survival (PMTR, HR = 0.403, 95% CI 0.384-0.423, P < 0.001; PTR, HR = 0.515, 95% CI 0.496-0.534, P < 0.001). Furthermore, in patients undergoing surgery, patients with younger age, female, married status, LCRC and lower CEA level were prone to receiving PMTR. Conclusions: This analysis demonstrated that surgery was an independent prognostic factor for improved survival in mCRC. Patients with LCRC had better survival than patients with RCRC after surgery.

7.
Cancer Med ; 6(8): 1882-1892, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28707427

RESUMO

The survival risk following curative surgery for nonmetastatic colorectal cancer (CRC) may be over- or underestimated due to a lack of attention to nonlinear effects and violation of the proportional hazards assumption. In this paper, we aimed to detect and interpret the shape of time-dependent and nonlinear effects to improve the predictive performance of models of prognoses in nonmetastatic CRC patients. Data for nonmetastatic CRC patients diagnosed between 2004 and 2012 were obtained from the Surveillance Epidemiology End Results registry. Time-dependent and nonlinear effects were tested and plotted. A nonlinear model that used random survival forests was implemented. The estimated 5-year cancer-specific death rate was 17.95% (95% CI, 17.70-18.20%). Tumor invasion depth, lymph node status, age at diagnosis, tumor grade, histology and tumor site were significantly associated with cancer-specific death. Nonlinear and time-dependent effects on survival were detected. Positive lymph node number had a larger effect per unit of measurement at low values than at high values, whereas age at diagnosis showed the opposite pattern. Moreover, nonproportional hazards were detected for all covariates, indicating that the contributions of these risks to survival outcomes decreased over time. The nonlinear model predicted prognoses more accurately (C-index: 0.7934, 0.7933-0.7934) than did the Fine and Gray model (C-index: 0.7550, 0.7510-0.7583). The three-dimensional cumulative incidence curves derived from nonlinear model were used to identify the change points of the risk trends. It would be useful to implement these findings in treatment plans and follow-up surveillance in nonmetastatic CRC patients.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Dinâmica não Linear , Prognóstico , Programa de SEER , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
8.
Biochem Biophys Res Commun ; 491(2): 530-536, 2017 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-28389245

RESUMO

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Timol/farmacologia , Acetilcisteína/farmacologia , Antracenos/farmacologia , Antineoplásicos Fitogênicos/antagonistas & inibidores , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Transformada , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Depuradores de Radicais Livres/farmacologia , Humanos , Imidazóis/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Piridinas/farmacologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Timol/antagonistas & inibidores , Urotélio/efeitos dos fármacos , Urotélio/metabolismo , Urotélio/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Oncotarget ; 7(44): 72263-72275, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27708217

RESUMO

BACKGROUND: Primary colorectal lymphoma (PCL) is a rare colorectal malignancy. The standard treatment and prognostic factors of PCL remain unexplored. Therefore, a large population-based study should be conducted to provide a detailed review of this disease. METHODS: We extracted the data of eligible patients with PCL registered in the SEER database from 1973 to 2011. All statistical analyses were performed using SPSS 19.0. RESULTS: A total of 2050 (61.3%) of the 3342 patients with PCL underwent surgical intervention, and 1292 (38.7%) patients received no surgical treatment. The median overall survival was 95 months, and patients receiving surgery exhibited significantly prolonged survival (adjusted HR =0.69, P <0.001). Young age, early tumor stage, and indolent lymphoma were independent predictors of improved survival. Further survival analyses demonstrated the potential benefit of surgery in patients with early tumor stage, right-sided lesions, or diffuse large B-cell PCL. Conversely, surgical intervention did not improve the survival of patients with advanced-stage, left-sided, or indolent PCL. CONCLUSION: PCL is a rare tumor that can be effectively treated. Surgical intervention may play an important role in the treatment of PCL. Early tumor stage, a right-sided lesion, and diffuse large B-cell histological PCL seem to be the clinical characteristics of optimal surgical candidates.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Linfoma/mortalidade , Linfoma/cirurgia , Programa de SEER/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/patologia , Cirurgia Colorretal/estatística & dados numéricos , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
Oncotarget ; 7(19): 28570-8, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27086913

RESUMO

PURPOSE: The association chemokine receptor CCR3 with breast cancer subtypes and relapse-free survival is unknown. RESULTS: The overall expression (either intratumoral or peritumoral) of CCR3 was not associated with tumor size, lymph node status, age, and subtype. When we confined the analysis in samples without peritumoral stromal CCR3 expression, intratumoral expression of CCR3 was associated with breast cancer subtype (P=0.04). Tumors with high expression of CCR3 were more likely to be luminal-like rather than TNBC or HER2-enriched cancers. Moreover, high mRNA expression of CCR3 was related with improved relapse-free survival in luminal-A/B (P<0.001). The subsequent sensitivity analysis using the systemically untreated patients confirmed that higher mRNA expression of CCR3 was a robust prognostic factor for luminal-A (P=0.0025) and luminal-B (P=0.088), but not for HER2-enriched (P=0.21) and TNBC (P=0.86). In the independent cohort, the positive association between increased expression of CCR3 and improved distant relapse-free survival was also observed. METHODS: We determined the expression level of CCR3 in 150 cases with breast cancer by using immunohistochemistry (IHC) assay, for both intratumoral and peritumoral stroma, and investigated the effect of CCR3 expression on relapse-free survival according to subtype using cases from publicly available datasets, in the whole group (N=3557) and in the patients without adjuvant systemic treatment (N=1005), respectively. Moreover, the survival outcomes were validated in another independent cohort including 508 breast cancer patients treated with neoadjuvant chemotherapy. CONCLUSIONS: Our data indicate that intratumoral expression of CCR3 in breast cancer is associated with improved relapse-free survival in patients with luminal-like disease.


Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Receptores CCR3/genética , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Receptor ErbB-2/metabolismo , Receptores CCR3/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Adulto Jovem
11.
Oncol Lett ; 11(1): 731-734, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870275

RESUMO

α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation of common adenocarcinoma cells, reverting them to a cancer stem cell state and producing AFP or hepatoid differentiation. Consequently, therapy targeted to the HGF/c-Met signaling pathway may potentially be effective for the treatment of AFP-producing colorectal adenocarcinoma.

12.
Medicine (Baltimore) ; 95(6): e2711, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26871810

RESUMO

The gradient monotonicity of existing tumor, node, metastases staging systems for colorectal cancer is unsatisfactory. Our proposed T-plus staging system strengthens weighting of the T stage. In this study, applicability of the T-plus staging system was verified with data of a Chinese colorectal cancer center.Records of 2080 nonmetastatic, advanced cancer patients undergoing colorectal cancer surgery from 1985 to 2011 were reviewed for T, N stage pathology and follow-up information. Using overall and disease-specific survival data, the 7th edition tumor, node, metastases staging system and the T-plus staging system were compared for stage homogeneity and discrimination and gradient monotonicity.For gradient monotonicity, the T-plus staging system was superior for both colon and rectal cancer. With Kaplan-Meier survival curves, the T-plus staging system discriminated among different stages, and the corresponding survival was inversely associated with the stage. However, for the 7th edition tumor, node, metastases staging system, stage IIIa had a better prognosis than stage II for rectal cancer and stage I for colon cancer. For homogeneity within the same stage and discrimination between different stages, the 2 staging systems were similar for colorectal cancer, but the T-plus system was clearly better for colon cancer.The T-plus staging system provides good gradient monotonicity. For future colorectal cancer staging systems, we propose replacement of lymph node status as the criterion to discriminate colorectal cancer stage II and stage III with greater weighting of the T stage.


Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida
13.
PLoS One ; 9(9): e107872, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25243406

RESUMO

OBJECTIVE: To assess the impact of oxaliplatin-containing adjuvant chemotherapy on the survival of patients with locally-advanced rectal cancer. METHODS: Data on patients with pathologically-confirmed T3/4 or N1/2 rectal cancer who accepted radical surgery at our center from January 2002 to June 2009 were reviewed retrospectively. The patients' 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by comparing those who accepted radical surgery only (Group S) with those who accepted radical surgery and oxaliplatin-containing adjuvant chemotherapy (Group SO). RESULTS: A total of 236 patients were analyzed (Group S 135; Group SO 101). Group S patients were older and had a higher proportion with stage II disease and more perioperative complications than those in Group SO (P<0.05). The OS and DSS of patients with stage III disease under 50 years of age or with mucinous adenocarcinoma were higher in Group SO than Group S (P<0.05). In addition, the OS of patients with stage N2b disease was higher in Group SO than Group S (P = 0.016), and the OS of patients with stage N1a or N2b disease who received more than 8 weeks of oxaliplatin-containing chemotherapy was also higher in Group SO than Group S (P<0.05). Although the OS and DSS of patients with stage II disease in Group SO showed a tendency towards improvement, the differences between the groups were not statistically significant. CONCLUSION: Adjuvant oxaliplatin-containing chemotherapy can improve the survival of patients with locally-advanced low and middle rectal cancers in comparison with observation. Randomized, prospective trials are warranted to confirm this benefit of oxaliplatin for rectal cancer.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina , Neoplasias Retais/patologia , Taxa de Sobrevida
14.
Oncol Lett ; 8(4): 1455-1460, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25202349

RESUMO

Gastrointestinal stromal tumors (GISTs) are rare in the rectum. Radical surgery, such as an abdominoperineal resection, is necessary for large rectal GISTs, which can result in the loss of function of involved organs. Imatinib mesylate can be used as perioperative therapy and may reduce tumor size, and it is now approved for use in the adjuvant therapy of locally resected anorectal GISTs. The present study describes two cases of large rectal GISTs, for which abdominoperineal resections were initially planned. The two patients received pre-operative imatinib mesylate treatment, and the therapeutic response was assessed by magnetic resonance imaging. Finally, transsacral local resection was successfully performed for these two GISTs. A macroscopically complete resection was achieved, and microscopically, the resection margin was negative. One patient experienced the complication of rectal leakage, which was successfully managed by drainage. No recurrence occurred in the two patients after more than two years. Pre-operative imatinib mesylate therapy with subsequent transsacral local resection for selected rectal GISTs is a feasible treatment modality and can prevent extended surgery.

15.
J Zhejiang Univ Sci B ; 15(8): 701-12, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25091988

RESUMO

OBJECTIVE: Cancer stromal fibroblasts are important members of the cancer microenvironment. In this study, we determined the effect of sunitinib, a small molecule tyrosine kinase inhibitor, on the primary human colonic fibroblasts. METHODS: Cell cycle analysis and cell proliferation assays were performed to evaluate the inhibitory effect of sunitinib in vitro. Western-blot analysis was performed to evaluate variations in the levels of phosphorylated platelet-derived growth factor receptor ß (PDGFR-ß), Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibroblasts in nude mice was employed to test anti-growth efficacy in vivo. RESULTS: Sunitinib was found to effectively inhibit the growth of primary colonic fibroblasts. Low-dose sunitinib blocked the PDGF-BB-induced cell proliferation and PDGFR-ß signaling. Co-injection of SW620 cells and colonic fibroblasts in nude mice generated greater tumor volumes than single injection of SW620 cells. Sunitinib treatment inhibited the SW620 cell+colonic fibroblast tumor growth more effectively than treatment of 5-fluorouracil. CONCLUSIONS: Sunitinib mesylate inhibited the proliferation of primary human colonic fibroblasts through target-inhibited PDGFR signaling in vitro and in vivo.


Assuntos
Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Indóis/farmacologia , Pirróis/farmacologia , Animais , Antineoplásicos/farmacologia , Becaplermina , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colo/metabolismo , Neoplasias do Colo/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fluoruracila/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-sis/antagonistas & inibidores , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Sunitinibe , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
World J Gastroenterol ; 20(17): 5104-12, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24803826

RESUMO

AIM: To verify that the T stage has greater weight than the N stage in the staging of colorectal cancer. METHODS: Open data from the Surveillance, Epidemiology, and End Results program were reviewed and analyzed according to the T stage, N stage, and patients' observed survival (OS). The relative weights of the T and N stages were calculated by multiple linear regressions based on their impact on survival. Risk scores for 25 TN categories were then calculated from the T and N stage relative weights, and a rearranged tumor node metastasis (TNM) staging system was proposed via a cluster analysis of the TN scores. RESULTS: Both T and N stages significantly affect the OS of patients with colorectal cancer. Moreover, the T stage has greater weight than the N stage in the TNM staging system of colorectal cancer. For colon cancer, the relative T and N stage weights were 0.58 and 0.42, respectively, and for rectal cancer, the relative T and N stage weights were 0.61 and 0.39, respectively. On the basis of cluster analysis of the TN scores, T1N1a was classified to stage I, and T2N1a-1b and T1N1b-2a were classified to stage II in our revised TNM staging system for both colon and rectal cancer. For colon cancer, T4bN0 was classified to stage IIIa, but for rectal cancer, it was classified to stage IIIb. CONCLUSION: As the T stage affects colorectal cancer survival more significantly than the N stage, the TNM staging should be revised by relative T stage weight.


Assuntos
Neoplasias Colorretais/patologia , Estadiamento de Neoplasias/métodos , Análise por Conglomerados , Neoplasias Colorretais/mortalidade , Humanos , Modelos Lineares , Valor Preditivo dos Testes , Fatores de Risco , Programa de SEER , Análise de Sobrevida , Fatores de Tempo , Estados Unidos
17.
Zhonghua Zhong Liu Za Zhi ; 35(2): 148-53, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23714673

RESUMO

OBJECTIVE: To evaluate the clinical value of radial endorectal ultrasound (ERUS) in the assessment of preoperative staging of rectal carcinoma. METHODS: One hundred and ten patients with rectal cancer underwent preoperative endorectal ultrasound (ERUS) examination in our hospital from February 2010 to September 2011. ERUS was performed using a Hitachi 900, Hitachi HI Vision Preirus US scanner, with a 5 - 10 MHz rigid rotating radial transducer and a focal length of 2 - 5 cm. The size, shape, echo pattern, infiltration depth, degree of circumferential involvement, extra-rectal invasion of the lesions and lymph node involvement were observed. The results of ERUS staging were compared with histopathological findings of the surgical specimens. RESULTS: The accuracy of ERUS for T staging was 91.4%. The accuracy of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.7%, 88.2%, 88.2% and 96.4%, respectively. The sensitivity of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.3%, 72.7%, 85.4% and 71.4%, respectively. The specificity of ERUS in diagnosing stage T1, T2, T3, T4 cancer was 92.9%, 92.0%, 90.3% and 100.0%, respectively. Comparing the consistency of preoperative T-staging and postoperative pathological results, the Kappa value was 0.75, with a considerable consistency. The sensitivity, specificity, and accuracy of ERUS in the assessment of lymph node metastasis were 74.2%, 89.9% and 85.5%, respectively. Comparing the consistency of preoperative N-staging and postoperative pathological results, the Kappa value was 0.64, with a considerable consistency. CONCLUSIONS: ERUS is a practical and accurate tool in assessment of preoperative staging of rectal tumors in regard to tumor invasion depth (T) and regional lymph node status (N), with advantages of simple operation, less pain, and high accuracy.


Assuntos
Endossonografia/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Neoplasias Retais/cirurgia , Reto/patologia , Reto/cirurgia
18.
Oncol Lett ; 4(6): 1191-1194, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23197997

RESUMO

Recently, the coexistence of gastrointestinal stromal tumors (GISTs) with other neoplasms has been studied with increasing frequency. Coexistence of pancreatic cancer with GISTs remains a rarity; however, here, we report a very rare case of adenosquamous carcinoma (ASC) of the uncinate process of the pancreas with synchronous GISTs of the stomach in a 62-year-old female. The patient presented with epigastric discomfort and vomiting. Radiographic imaging revealed two masses; one located at the body of the stomach and the other located at the uncinate process of the pancreas. Intraoperatively, a fine needle aspiration biopsy was conducted in the uncinate process of the pancreas, which revealed the malignancy of the masses. A pancreaticoduodenectomy and partial gastrectomy were then conducted, and subsequent pathological examinations identified an ASC of the pancreas and a GIST of the stomach. In our case, contrary to the majority of previous cases of synchronous GISTs and other malignancies, GIST was not an incidental finding. The initial suspicion on the GIST as the underlying cause of clinical symptoms led to the discovery of the ASC of the uncinate process of the pancreas.

19.
J Zhejiang Univ Sci B ; 13(3): 159-67, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22374607

RESUMO

OBJECTIVE: Cancer-associated fibroblasts (CAFs) are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. METHODS: Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was conducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip platform. RESULTS: Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of α-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio (m/z) 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin ß-4-like protein 3, and tight junction-associated protein 1. CONCLUSIONS: Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.


Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Proteômica/métodos , Idoso , Idoso de 80 Anos ou mais , Técnicas de Cultura de Células , Separação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Análise Serial de Proteínas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Células Tumorais Cultivadas , Microambiente Tumoral/fisiologia
20.
BMC Cancer ; 11: 494, 2011 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-22111914

RESUMO

BACKGROUND: Laparoscopy-assisted surgery, fast-track perioperative treatment are both increasingly used in colorectal cancer treatment, for their short-time benefits of enhanced recovery and short hospital stays. However, the benefits of the integration of the Laparoscopy-assisted surgery, fast-track perioperative treatment, and even with the Xelox chemotherapy, are still unknown. In this study, the three treatments integration is defined as "Fast Track Multi-Discipline Treatment Model" for colorectal cancer and this model extends the benefits to the whole treatment process of colorectal cancer. The main purpose of the study is to explore the feasibility of "Fast Track Multi-Discipline Treatment" model in treatment of colorectal cancer. METHODS: The trial is a prospective randomized controlled study with 2 × 2 balanced factorial design. Patients eligible for the study will be randomized to 4 groups: (I) Laparoscopic surgery with fast track perioperative treatment and Xelox chemotherapy; (II) Open surgery with fast track perioperative treatment and Xelox chemotherapy; (III) Laparoscopic surgery with conventional perioperative treatment and mFolfox6 chemotherapy; (IV) Open surgery with conventional perioperative treatment and mFolfox6 chemotherapy. The primary endpoint of this study is the hospital stays. The secondary endpoints are the quality of life, chemotherapy related adverse events, surgical complications and hospitalization costs. Totally, 340 patients will be enrolled with 85 patients in each group. CONCLUSIONS: The study initiates a new treatment model "Fast Track Multi-Discipline Treatment" for colorectal cancer, and will provide feasibility evidence on the new model "Fast Track Multi-Discipline Treatment" for patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos Clínicos , Neoplasias Colorretais/terapia , Laparoscopia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Tempo de Internação , Leucovorina/administração & dosagem , Estudos Prospectivos
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