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1.
Anticancer Res ; 40(10): 5371-5378, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988856

RESUMO

BACKGROUND/AIM: 18 kDa Translocator protein (TSPO) is a mitochondrial protein up-regulated in colorectal carcinoma (CRC). Our purpose was to develop a TSPO-targeted doxorubicin prodrug (Dox-TSPO) which can be loaded onto drug-eluting beads for transarterial chemoembolization. Furthermore, we evaluated its loading and release kinetics and effects on cell viability. MATERIALS AND METHODS: N-Fmoc-DOX-14-O-hemiglutarate was coupled with a TSPO ligand, 6-TSPOmbb732, using classical N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate coupling to produce Dox-TSPO. Loading and elution studies were performed using DC beads™. Cell viability studies were performed using CellTiter-Glo® Luminescent Cell Viability Assay. RESULTS: Dox-TSPO was successfully synthesized and readily loaded onto and eluted from DC beads™, albeit at a slower rate than free doxorubicin. CRC cell lines expressing TSPO were 2- to 4- fold more sensitive to Dox-TSPO compared to free doxorubicin at 72 h. CONCLUSION: Dox-TSPO is a promising candidate for targeted and directed cancer treatment of CRC liver metastases.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/farmacologia , Pró-Fármacos/farmacologia , Receptores de GABA/genética , Proteínas de Transporte/química , Proteínas de Transporte/farmacologia , Linhagem Celular Tumoral , Quimioembolização Terapêutica/métodos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Humanos , Pró-Fármacos/química , Receptores de GABA/química
2.
N Z Med J ; 133(1520): 15-26, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994590

RESUMO

AIMS: To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand. METHODS: This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors. RESULTS: 27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Maori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy. CONCLUSIONS: Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Maori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Tratamento Farmacológico/métodos , Disparidades em Assistência à Saúde/etnologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Tratamento Farmacológico/economia , Grupos Étnicos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Expectativa de Vida/etnologia , Expectativa de Vida/tendências , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Nova Zelândia/etnologia , Fatores de Tempo
3.
N Engl J Med ; 383(13): 1207-1217, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32955176

RESUMO

BACKGROUND: No therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C. METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was safety. Key secondary end points were pharmacokinetics and objective response, as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS: A total of 129 patients (59 with NSCLC, 42 with colorectal cancer, and 28 with other tumors) were included in dose escalation and expansion cohorts. Patients had received a median of 3 (range, 0 to 11) previous lines of anticancer therapies for metastatic disease. No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma. CONCLUSIONS: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effects occurred in 11.6% of the patients. (Funded by Amgen and others; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/genética
4.
Life Sci ; 259: 118395, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32905830

RESUMO

In recent years, natural products have increasingly attracted more attention because of their potential anticancer activity and low intrinsic toxicity. Hispidulin is a natural flavonoid with a wide range of biological activities, including anti-inflammatory, antifungal, antiplatelet, anticonvulsant, anti-osteoporotic, and notably anticancer activities. Numerous in vivo and in vitro studies have shown that hispidulin, as a potential anticancer drug, affects cell proliferation, apoptosis, cell cycle, angiogenesis, and metastasis. Moreover, hispidulin exhibits synergistic anti-tumor effects when combined with some common clinical anticancer drugs (e.g., gemcitabine, 5-fluoroucil, sunitinib, temozolomide, and TRAIL). The combination of hispidulin and chemotherapeutic drugs reduces the efflux of chemotherapeutic drugs, enhances the chemosensitivity of cancer cells, and reverses drug resistance. Herein, we outlined the anticancer effects of hispidulin in various cancers and its intracellular molecular targets and related mechanisms of its anticancer activity. Based on the available literature, it can be established that hispidulin has significant potential to become an important complementary medicine for cancer prevention and treatment. However, more in-depth in vitro and in vivo studies should be conducted to support its translation from bench to bedside.


Assuntos
Antineoplásicos/uso terapêutico , Flavonas/uso terapêutico , Flavonoides/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico
5.
Medicine (Baltimore) ; 99(39): e22357, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991451

RESUMO

BACKGROUND: The incidence and mortality of colorectal cancer are high. Chemotherapy is currently the commonly used therapeutic scheme, but there are drug resistance and toxic and side effects. Kanglaite (KLT) injection is a broad-spectrum anticancer drug extracted from Semen Coicis (Yi Yi Ren), which has been widely used in the treatment of colorectal cancer. Clinical practice shows that KLT injection combined with chemotherapy has certain therapeutic advantages, but there is a lacking of evidence of evidence-based medicine. The purpose of this study is to systematically investigate the efficacy and safety of KLT injection combined with chemotherapy in the treatment of colorectal cancer. METHODS: Randomized controlled trials of KLT injection combined with chemotherapy in the treatment of colorectal cancer were retrieved from English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, Wanfang, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biological and Medical database), as well as searching Baidu academic and Google academic manually, and the retrieval time was from their establishment to August 2020. Two researchers independently conducted data extraction and literature quality evaluation on the quality of the included literatures, and meta-analysis was conducted on the included literatures using RevMan 5.3 (developed by the UK's International Cochrane Collaboration). RESULTS: This study assessed the efficacy and safety of KLT injection combined with chemotherapy in the treatment of colorectal cancer by effective rate, Karnofsky Performance Status, Carcinoemybryonic Angtigen remission rate, pain remission rate, and incidence of adverse reactions etc. CONCLUSIONS:: This study will provide reliable evidence-based evidence for the clinical application of KLT injection combined with chemotherapy in the treatment of colorectal cancer. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/EKVAF.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dor do Câncer/tratamento farmacológico , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Avaliação de Estado de Karnofsky , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
6.
Anticancer Res ; 40(9): 4843-4856, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878772

RESUMO

Aberrant fatty acid (FA) metabolism has long been recognized in colorectal cancer (CRC) cells. Since de novo lipogenesis is required for CRC tumour growth and survival, the inhibition of FA metabolism is a promising potential therapeutic target. Inhibition of the opposite process, ß-oxidation of FAs, has also showed promising results in many CRC models. For patients with CRC, both FA synthesis and ß-oxidation inhibitors are promising potential therapeutic options as monotherapies or as combination therapies with other anticancer agents. In this review, we discuss recent reports concerning inhibitors of FA synthesis and ß-oxidation in various CRC models. The exact mechanisms of action of the selected compounds described in this review remain unknown and require precise evaluation before the development of new successful therapies for CRC is possible.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Inibidores Enzimáticos/farmacologia , Ácidos Graxos/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos
7.
PLoS One ; 15(8): e0235319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810173

RESUMO

Aberrant activation of the Wnt signalling pathway is required for tumour initiation and survival in the majority of colorectal cancers. The development of inhibitors of Wnt signalling has been the focus of multiple drug discovery programs targeting colorectal cancer and other malignancies associated with aberrant pathway activation. However, progression of new clinical entities targeting the Wnt pathway has been slow. One challenge lies with the limited predictive power of 2D cancer cell lines because they fail to fully recapitulate intratumoural phenotypic heterogeneity. In particular, the relationship between 2D cancer cell biology and cancer stem cell function is poorly understood. By contrast, 3D tumour organoids provide a platform in which complex cell-cell interactions can be studied. However, complex 3D models provide a challenging platform for the quantitative analysis of drug responses of therapies that have differential effects on tumour cell subpopulations. Here, we generated tumour organoids from colorectal cancer patients and tested their responses to inhibitors of Tankyrase (TNKSi) which are known to modulate Wnt signalling. Using compounds with 3 orders of magnitude difference in cellular mechanistic potency together with image-based assays, we demonstrate that morphometric analyses can capture subtle alterations in organoid responses to Wnt inhibitors that are consistent with activity against a cancer stem cell subpopulation. Overall our study highlights the value of phenotypic readouts as a quantitative method to asses drug-induced effects in a relevant preclinical model.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Organoides/efeitos dos fármacos , Tanquirases/antagonistas & inibidores , Adulto , Animais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imageamento Tridimensional , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Organoides/patologia
8.
Gan To Kagaku Ryoho ; 47(8): 1264-1267, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32829370

RESUMO

In the 9th edition Japanese Classification of Colorectal Carcinoma, Stage Ⅱ and Stage Ⅲ colorectal cancer(CRC)were subdivided by TNM classification on invasion and number of lymph node metastases. We studied prognostic comparison and relation of adjuvant chemotherapy at the new classification. We included 400 cases with resected Ⅱ and Ⅲ CRC from 2007 to 2014. Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc were 97/68/20/24/124/67 cases. Adjuvant chemotherapy was performed at 19/32/45/66/59/70% in Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc, with or without adjuvant chemotherapy at each stage survival rates were compared. In Ⅱa/Ⅱb/Ⅱc, DSS was 97/97/82% and DFS was 89/88/76%, and the prognosis of Ⅱc was significantly worse. In Ⅲa/Ⅲb/Ⅲc, DSS was 95/86/57% and DFS was 82/77/41%. By the presence or absence of adjuvant chemotherapy, significantly differences were obtained at Ⅲb and Ⅲc. Prognosis of Ⅱc was almost same as Ⅲb, and prognosis of Ⅲa was almost same as Ⅱb. Therefore, we considered adjuvant chemotherapy with oxaliplatin should be performed to Ⅱc, Ⅲb, and Ⅲc.


Assuntos
Neoplasias Colorretais , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Humanos , Japão , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
9.
Int J Nanomedicine ; 15: 5417-5432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801697

RESUMO

Introduction: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy. Materials and Methods: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment. Results: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively. Discussion: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.


Assuntos
Celulose/química , Portadores de Fármacos/química , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Fluoruracila/farmacocinética , Células HCT116 , Humanos , Neoplasias Nasofaríngeas/tratamento farmacológico , Oryza/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios X
10.
Int J Nanomedicine ; 15: 5445-5458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801699

RESUMO

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Fluoruracila/administração & dosagem , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Disponibilidade Biológica , Portadores de Fármacos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacocinética , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/química
11.
Future Oncol ; 16(28): 2191-2195, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32857603

RESUMO

Background: Telemedicine is seen as a savior during the COVID-19 pandemic. Materials & methods: This study is a descriptive cross-sectional study conducted with cancer patients who were interviewed via telemedicine from a tertiary care comprehensive oncology center. Results: A total of 421 patients were included in the study and 118 of them (28.0%) were >65 years old. Communication was provided most frequently by voice call (n = 213; 50.5%). The majority of the patients contacted by telemedicine had breast cancer (n = 270; 64.1%). For 135 patients (32.1%) no further examination or intervention was required and the previously planned follow-up visit was postponed by the clinician. Conclusion: This study showed that telemedicine could open a new era for medical oncology specialists.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer , Infecções por Coronavirus/prevenção & controle , Oncologia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Telemedicina/organização & administração , Administração Oral , Adulto , Assistência ao Convalescente/métodos , Assistência ao Convalescente/organização & administração , Assistência ao Convalescente/normas , Assistência ao Convalescente/tendências , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Betacoronavirus/patogenicidade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama Masculina , Institutos de Câncer/organização & administração , Institutos de Câncer/normas , Institutos de Câncer/tendências , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Estudos Transversais , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Controle de Infecções/organização & administração , Controle de Infecções/normas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Oncologia/métodos , Oncologia/normas , Oncologia/tendências , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/normas , Conduta do Tratamento Medicamentoso/tendências , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Telemedicina/normas , Telemedicina/tendências
12.
Medicine (Baltimore) ; 99(27): e21155, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629751

RESUMO

BACKGROUND: Brucea javanica oil emulsion injection (BJOEI) has been widely applied as a promising adjunctive drug for colorectal carcinoma (CRC). However, the exact effects and safety of BJOEI remains controversial. In this study, we aimed to summarize the efficacy and safety of BJOEI for the treatment of advanced CRC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: Eligible prospective controlled clinical trials were searched from PubMed, Cochrane Library, Google Scholar, Medline, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese BioMedical Database (CBM), China Scientific Journal Database (VIP), China National Knowledge Infrastructure (CNKI) and Wanfang Database. Papers in English or Chinese published from January 2000 to May 2020 will be included without any restrictions. The clinical outcomes including therapeutic effects, quality of life (QoL), immune function and adverse events, were systematically evaluated.Study selection and data extraction will be performed independently by 2 reviewers. Review Manager 5.3 and Stata 14.0 were used for data analysis, and a fixed or random-effect model will be used depending upon the heterogeneity observed between trials. Subgroup and meta-regression analysis will be carried out depending on the availability of sufficient data. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: Our study will draw an objective conclusion of the effects and safety of BJOEI for advanced CRC, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for CRC patients.INPLASY registration number: INPLASY202060014.


Assuntos
Brucea/efeitos adversos , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/tratamento farmacológico , Emulsões/administração & dosagem , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Colorretais/psicologia , Emulsões/uso terapêutico , Feminino , Humanos , Injeções/métodos , Masculino , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(27): e20944, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629699

RESUMO

BACKGROUND: Colorectal cancer is the second commonly seen cancer around the world and accounts for 13% of all human cancers. Among them, 25% of all case were diagnosed with metastasis and 50% occurs metastasis during the development of disease. Cetuximab is a chimeric monoclonal antibody against epidermal growth factor receptor, and is used for treatment of metastatic colorectal cancer alone or combined with chemotherapy or radiation therapy. Integrin-beta 1 (ITGB1), which is also known as CD29, and plays an important role in development of malignant cancers. However, the effect of ITGB1 in promoting the anti-tumor effect of cetuximab is not fully understand. METHODS: The model of ITGB1 inhibition and overexpression was firstly constructed in LS174T cells, and the viability of cells in each group was detected using CCK-8 assay. The expression of key factors in tumor formation process at transcription level was detected using real-time quantitative polymerase chain reaction method. The expression of key proteins in metastasis process, cell apoptosis and activation of Ras/Raf/MEK signaling pathway was detected using western blotting analysis. And the concentration of key factors of in tumor formation process in cultured medium of LS174T cells were detected using enzyme-linked immunosorbent assay method. RESULTS: We found that cetuximab could inhibit the proliferation of LS174T cells, and inhibition of ITGB1 enhanced this effect while overexpression of ITGB1 reduced this effect. We further found that cetuximab could inhibit the expression and secretion of extracellular matrix degradation related molecules in cultured medium and transcription level. Besides, we also found that the expression of key factors in angiogenesis and extracellular matrix degradation related proteins were also reduced after cetuximab treatment. These effects might be mediated by Ras/Raf/MAPK signaling pathway and enhanced after inhibition of ITGB1 expression. CONCLUSION: Inhibition of ITGB1 might be a new therapeutic method in colorectal cancer.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Cetuximab/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Integrina beta1/efeitos dos fármacos , Antineoplásicos Imunológicos/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Cetuximab/uso terapêutico , Neoplasias Colorretais/patologia , Humanos , Integrina beta1/metabolismo
14.
Cancer Treat Rev ; 88: 102059, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32622273

RESUMO

Colon cancer (CC) has the highest incidence rate among gastrointestinal cancers and ranks the third in mortality among all cancers, which contributes to the current CC burden and constitutes a major public health issue. While therapeutic strategies for stage I, III, and IV CC are standardized, those for stage II CC remain debatable. The choice of adjuvant chemotherapy for patients with stage II CC depends on stage (pT4) and grade (high) of the disease, the presence of venous, perinervous, and/or lymphatic emboli, or the need of suboptimal surgery (tumor with initial occlusion or perforation needing emergency surgeries, <12 lymph nodes harvested). Several prognostic factors that have been validated in retrospective studies can potentially define a population of CC patients at low and high-risk for reccurence. The role of biomarkers is becoming increasingly important for the future personalized treatment options. We conducted a systematic overview of potential prognostic biomarkers with possible clinical implications in stage II CC.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico
15.
Anticancer Res ; 40(8): 4687-4694, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727793

RESUMO

BACKGROUND/AIM: The Japanese apricot "Prunus mume" is a traditional Japanese medicine. MK615, a compound extract from Prunus mume has been reported to have anti-tumor effects. Herein, we used 3D floating (3DF) culture to evaluate the anticancer effects of MK615 against human colorectal cancer (CRC) cells that contain mutant (mt) KRAS. MATERIALS AND METHODS: HKe3 cells exogenously expressing mtKRAS (HKe3-mtKRAS) were treated with MK615 in 3DF cultures. The protein levels of hypoxia-inducible factor 1 (HIF-1) and E-cadherin were quantified by western blotting. RESULTS: MtKRAS enhanced hypoxia tolerance via up-regulation of HIF-1. The expression of HIF-1 protein was suppressed by constitutive overexpression of E-cadherin in CRC HCT116 spheroids. MK615 increased the expression of E-cadherin and decreased the expression of HIF-1 in HKe3-mtKRAS. These results suggest that MK615 suppresses hypoxia tolerance by up-regulation of E-cadherin in CRC cells with mtKRAS. CONCLUSION: MK615 exhibits properties useful for the potential treatment of CRC patients with mtKRAS.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Hipóxia Celular/fisiologia , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Regulação para Cima/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prunus/química , Ativação Transcricional/efeitos dos fármacos
16.
Gan To Kagaku Ryoho ; 47(7): 1109-1111, 2020 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-32668863

RESUMO

We present the case of a 75-year-old woman who received CapeOX plus Bmab therapy(capecitabine, oxaliplatin, and bevacizumab)after primary excision for an unresectable advanced sigmoid colon cancer with remote metastasis. Pneumatosis intestinalis(i.e., the presence of isolated gas in the abdominal cavity)was revealed accidentally during a periodical imaging examination in the small intestine and transverse colon, albeit no subjective symptoms were reported. Owing to the absence of definitive evidence of pneumatosis intestinalis and gastrointestinal perforation, the patient was diagnosed with idiopathic pneumatosis intestinalis. Bmab was discontinued, and CapeOX therapy alone was continued after follow-up. Approximately 4 months later, pneumatosis intestinalis had completely disappeared. Bmab is a vascular endothelial growth factor antibody with well-known side effect of gastrointestinal-perforation. However, there have been few reports on pneumatosis intestinalis; to our knowledge, there have been no reports on pneumatosis intestinalis associated with colorectal cancer in Japan. Further, the report suggests the need for appropriate and immediate management of pneumatosis intestinalis following diagnosis.


Assuntos
Bevacizumab/efeitos adversos , Neoplasias Colorretais , Pneumatose Cistoide Intestinal/induzido quimicamente , Idoso , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Japão , Fator A de Crescimento do Endotélio Vascular
17.
Gan To Kagaku Ryoho ; 47(7): 1117-1119, 2020 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-32668865

RESUMO

We present case reports of 4 patients on hemodialysis with Stage Ⅳ colorectal cancer who received regular dose bevacizumab( twice per week)plus a daily dose of UFT chemotherapy. This regimen was safe and effective in the long-term for these patients without requiring changes in the hemodialysis schedule. The 4 patients were 71, 75, 67, and 66-year-old men who received bevacizumab 32, 49, 22, and 63(ongoing)times, respectively. Progression-free survivalwas 16, 28, 15, and 30 months, respectively; no severe side effects occurred during this therapy. It is possible that the bevacizumab plus UFT regimen may be acceptable in patients with Stage Ⅳ colorectal cancer receiving hemodialysis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais , Idoso , Bevacizumab , Neoplasias Colorretais/tratamento farmacológico , Humanos , Leucovorina , Masculino , Diálise Renal , Tegafur , Resultado do Tratamento
18.
Anticancer Res ; 40(7): 4157-4163, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620665

RESUMO

BACKGROUND/AIM: The efficacy of trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) plus bevacizumab as later-line treatment for metastatic colorectal cancer (mCRC) has been demonstrated. However, little is known about the impact of a usage history of bevacizumab in front-line treatment on the clinical benefit of combining bevacizumab with FTD/TPI. PATIENTS AND METHODS: A total of 62 patients with mCRC treated with FTD/TPI±bevacizumab was enrolled and assessed for chemotherapeutic efficacy and adverse events. RESULTS: Regardless of the usage history of bevacizumab in front-line treatment, the FTD/TPI plus bevacizumab group had a significantly better progression-free survival rate than the FTD/TPI monotherapy group, and no significant differences in the safety profile were observed between the two groups. CONCLUSION: Combining bevacizumab with FTD/TPI improves the survival outcomes with manageable toxicity, regardless of the usage history of bevacizumab in front-line treatment, in patients with mCRC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Pirrolidinas/uso terapêutico , Timidina Fosforilase/antagonistas & inibidores , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Uracila/uso terapêutico , Adulto Jovem
19.
Life Sci ; 257: 118065, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32659366

RESUMO

AIMS: Pyroptosis is a newly discovered inflammatory programmed cell death. This study was to investigate whether pyroptosis is involved in the anti-colorectal cancer process of FL118. MATERIALS AND METHODS: The relationship between NLRP3 and caspase-1 and colorectal cancer was analyzed by bioinformatics. MTT was used to detect the cell viability. Cell membrane integrity was examined by LDH release. Wound healing assay and Transwell were used to detect the cell migration and invasion respectively. TUNEL was to check the cell death. The expression of pyroptosis-related factors was detected using qRT-PCR, Western blotting, Immunofluorescence and Elisa. And H&E staining was used to detect the toxicity of FL118 in colorectal cancer. KEY FINDINGS: In vitro, FL118 significantly inhibited the proliferation, migration and invasion of colorectal cancer, and the morphological characteristics of pyroptosis were observed under the microscope. With the change of FL118 concentration, the release rate of LDH in the supernatant and the expression of pyroptosis-related factors emerged an increase. However, pyroptosis induced by FL118 was reversed with the participation of MCC950 and VX-765, which suppressed the antitumor effect of FL118. In vivo, the result in the xenograft animal model and lung metastasis model experimental showed that FL118 could activate pyroptosis and thus inhibit the metastasis of colorectal cancer. SIGNIFICANCE: FL118 restrains the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provides important evidence in the study on the role of pyroptosis and different tumors.


Assuntos
Antineoplásicos/farmacologia , Benzodioxóis/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Indolizinas/farmacologia , Piroptose/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/prevenção & controle , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 701-708, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683833

RESUMO

Objective: To identify the prognostic factors in metastatic colorectal cancer (mCRC) patients treated with cetuximab and establish a prognostic nomogram and validate its accuracy. Methods: A retrospective case-control study was conducted. Patients were selected as following criteria: patients with metastatic colorectal cancer(mCRC), which primary site confirmed by pathology and metastatic lesions confirmed by CT or MRI with at least one measurable and evaluable target lesion; patients' expected survival longer than 3 months; Eastern Cooperative Oncology Group (ECOG) score between 0 to 2; patients have signed informed consent; both KRAS and NRAS genes were wild-type; and at least 2 cycles of cetuximab combined with chemotherapy as the first-line regimen. Patients who met the following criteria were excluded: patients with incomplete clinicopathological and follow-up data; patients with severe diseases of vital organs such as heart, brain, lung, kidney, or other advanced malignant tumors; patients without informed consent. According to the above criteria, clinicopathological data of 95 patients with mCRC admitted in the Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine for first-line treatment with cetuximab from January 2010 to January 2017 were analyzed retrospectively. The Cox proportional hazards model was used to analyze the clinicopathological factors to determine the independent prognostic factors for progression-free survival(PFS). The R software was adopted to establish a prognostic nomogram model. Then, the nomograms of 6-month, 12-month and 18-month progression-free survivals (PFS) were drawn, and compared with the reality. The internal validation and accuracy of the nomogram were determined by the Bootstrap method and also the calculated concordance index (C-index). Results: The median follow-up time was 16.5 (2-43) months and the median PFS was 8.5 months. PFS at 6-,12- and 18-month was 73.7%, 35.8%, and 17.9%, respectively. ECOG score of 1-2 (HR=5.733, 95% CI:2.408-13.649, P<0.001), primary tumor was located in the ileocecal region (HR=5.880, 95% CI:1.645-21.023, P=0.006), Ki-67 index ≥45% (HR=3.574,95% CI:1.403-9.108,P=0.008), baseline D-dimer level ≥345 mg/L (HR=2.536,95% CI:1.531-7.396, P=0.012), NLR≥2.8 (HR=5.573,95% CI:2.107-14.740,P=0.001) and the combined treatment for FOLFOX (HR=0.465, 95% CI: 0.265-0.817, P=0.008) were independent risk factors for PFS of mCRC patients (all P<0.05). These independent risk factors were taken into account to construct a nomogram prediction model. The bootstrap method was used to perform internal validation, and the C-index of the nomogram prediction model in this study was 0.67 (95% CI: 0.64~0.71). The 6-, 12- and 18-month PFS predicted by the nomogram were consistent with the actual values. Conclusion: The nomogram model constructed by ECOG score, primary tumor site, Ki-67 index, baseline D-dimer level, baseline NLR and chemotherapy regimen may predict the prognosis of mCRC patients treated with cetuximab more accurately and individually, which can assist clinicians in making treatment decisions.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Nomogramas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/secundário , Humanos , Prognóstico , Estudos Retrospectivos
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