Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 10.393
Filtrar
1.
Anticancer Res ; 40(10): 5611-5620, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988885

RESUMO

BACKGROUND/AIM: Cancer stem cell characteristics and drug resistance of colorectal cancer are associated with failure of cancer treatment. In this study, we investigated the effects of PrPC on cancer stem cell characteristics, migration, invasion, and drug resistance of 5FU-resistant CRC cells. MATERIALS AND METHODS: PrPC negative and PrPC positive cells were isolated from 5FU-resistant CRC cells using magnetic activated cell sorting. Sphere formation, cancer stem cell marker expression, migration, invasion, and drug resistance were analyzed. RESULTS: PrPC positive cells showed increased sphere formation capacity and increased expression of cancer stem cell markers compared to PrPC negative cells. In addition, PrPC positive cells showed increased migration, invasion and drug resistance compared to PrPC negative cells. Furthermore, knockdown of PrPC abolished these effects. CONCLUSION: PrPC expression is important in CRC cell behavior, such as sphere formation, migration, invasion, and drug resistance. PrPC is an important therapeutic target for the treatment of CRC.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Proteínas Priônicas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos
2.
Gan To Kagaku Ryoho ; 47(7): 1125-1127, 2020 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-32668867

RESUMO

A male patient in his 80s, diagnosed with rectal cancer, underwent transverse colon resection(pT3, pN0, cM0, and pStage Ⅱa, RAS wild-type, BRAF-mutant). However, 19 months later, intraperitoneal metastasis was detected and the patient received 8 courses of mFOLFOX6 plus bevacizumab. Following the observation of an allergic reaction that was attributable to oxaliplatin, the regimen was changed to a total of 7 courses of sLV5FU2 plus bevacizumab. Subsequently, a marked decrease was observed in intraperitoneal metastasis. The patient completed sLV5FU2 plus bevacizumab chemotherapy. At 1 year after the marked decrease, the metastatic recurrence was not exacerbated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colo Transverso , Neoplasias do Colo/tratamento farmacológico , Neoplasias Peritoneais , Idoso de 80 Anos ou mais , Bevacizumab , Fluoruracila , Humanos , Leucovorina , Masculino , Compostos Organoplatínicos
3.
Nat Commun ; 11(1): 3606, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681016

RESUMO

Mitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The ß1-blocker nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients.


Assuntos
Antagonistas Adrenérgicos/farmacologia , Indutores da Angiogênese/farmacologia , Neoplasias da Mama/fisiopatologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Nebivolol/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas/genética , Proteínas/metabolismo
4.
Anticancer Res ; 40(8): 4331-4341, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727761

RESUMO

BACKGROUND/AIM: Adjuvant chemotherapy is recommended for a subgroup of colon cancer patients based on patient and tumour characteristics. Population-based data on the adoption of the prevailing guideline recommendations including the assessment of tumour mismatch repair (MMR) status are limited, while variations in treatment strategies may influence patient outcomes. Therefore, the aim of the study was to assess practice variation in adjuvant chemotherapy administration in colon cancer patients. PATIENTS AND METHODS: We examined the association between patient, demographic and tumour characteristics on the odds of being treated with adjuvant chemotherapy in a random sample of adult stage II-III colon cancer patients from the Dutch National Cancer Registry (2008-2015) and assessed its association with survival. RESULTS: The study population consisted of 2,044 patients of whom 18% (79 out of 450) were high-risk stage II and 65% (645 out of 997) were stage III colon cancer and received adjuvant chemotherapy. Chemotherapy administration differed between individual hospitals (high-risk stage II: 0-39%; p=0.01; stage III: 50-78%; p=0.06). Type of hospital (teaching versus academic) and the presence of a pT4 tumour were positively associated (high-risk stage II), and bowel perforation and examined regional lymph nodes (<10) were negatively associated (stage III) with adjuvant treatment. Higher age was associated with non-administration of adjuvant chemotherapy for both stages. Tumour MMR-status assessment increased from 9% to 23% (p<0.001), but 62% of high-risk stage II and 13% of stage III patients did not undergo guideline-recommended MMR-status testing. Adjuvant chemotherapy was correlated with survival for stage III (HR=0.4; 95%CI=0.3-0.5) but not for high-risk stage II patients (HR=1.2; 95%CI=0.7-2.2). CONCLUSION: Significant practice variation in the adjuvant treatment of colon cancer on hospital level was demonstrated, predominantly in high-risk stage II patients. The implementation of MMR testing was suboptimal. We recommend continuous monitoring of treatment patterns using population-based data, which should facilitate hospital auditing and improve guideline implementation and quality of care for colon cancer patients.


Assuntos
Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Idoso , Estudos de Coortes , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Sistema de Registros , Análise de Sobrevida
6.
Gan To Kagaku Ryoho ; 47(6): 989-992, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32541181

RESUMO

A 61-year-old man underwent CapeOX plus bevacizumab chemotherapyafter right hemicolectomyfor metastatic ascending colon cancer. On the 7th dayafter the first administration, he had sudden abdominal pain and nausea. Contrast-enhanced computed tomographyrevealed aortic thrombosis and a superior mesenteric artery(SMA)embolism that was considered to be associated with bevacizumab. Bevacizumab was discontinued and anticoagulation therapyusing heparin and urokinase was performed. Brain infarction of the left middle cerebral arteryoccurred on the 15th dayafter the first administration and thrombectomywas performed. Anticoagulation therapyusing heparin, bayaspirin, and edoxaban tosilate hydrate was performed. The aortic thrombosis and SMA embolism resolved with treatment, but the patient died following an increase in peritoneal dissemination. It should be noted that unexpectedlysevere aortic thrombosis occurred during the first administration of CapeOX plus bevacizumab for metastatic colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo , Trombose , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Capecitabina , Neoplasias do Colo/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos , Oxaliplatina , Trombose/induzido quimicamente
7.
Toxicol Appl Pharmacol ; 401: 115100, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32512070

RESUMO

(-)-Epigallocatechin-3-gallate (EGCG) is the main bioactive component in tea (Camellia sinensis) catechins, and exhibits potential antitumor activity against colorectal cancer (CRC). However, the underlying mechanisms are largely unclear. We investigated the effects of EGCG on activities of CRC cells and the exact molecular mechanism. We used human colon cancer cells (HT-29) and exposed them to EGCG at various concentrations. The MTT assay, flow cytometry, and TUNEL staining were used to study the underlying mechanisms of EGCG (proliferation, apoptosis, autophagy). Western blotting was used to measure expression of marker proteins of the cell cycle, apoptosis, and autophagy. Using a combined microarray-based transcriptomic and ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomic approach, we investigated the perturbed pathways induced by EGCG treatment at transcript and metabolite levels. Transcriptomic analyses showed that 486 genes were differentially expressed between untreated and EGCG-treated cells. Also, 88 differentially expressed metabolites were identified between untreated and EGCG-treated cells. The altered metabolites were involved in the metabolism of glutathione, glycerophospholipids, starch, sucrose, amino sugars, and nucleotide sugars. There was substantial agreement between the results of transcriptomics and metabolomics analyses. Our data indicate that the anticancer activity of EGCG against HT-29 cells is mediated by induction of cell-cycle arrest, apoptosis, and autophagy. EGCG modulates cancer-cell metabolic pathways. These results provide a platform for future molecular mechanistic studies of EGCG.


Assuntos
Anticarcinógenos/farmacologia , Catequina/análogos & derivados , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Metabolômica/métodos , Transcriptoma/efeitos dos fármacos , Anticarcinógenos/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Neoplasias do Colo/tratamento farmacológico , Células HT29 , Humanos , Transcriptoma/fisiologia
8.
Internist (Berl) ; 61(7): 699-710, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32494899

RESUMO

This article deals with the treatment of metastatic colorectal cancer (stage IV). The treatment goals and approaches are determined by the resectability status of the metastases: resectable liver and lung metastases are primarily resected and perioperative chemotherapy appears to be dispensable. In potentially resectable metastases, a conversion therapy is attempted to enable a potentially curative resection. In the case of nonresectability the treatment goal is palliative. Induction and maintenance therapy as well as drug holidays are suggested in an attempt to achieve extended survival while maintaining the quality of life, beginning with the best possible individual treatment. For some patients with stage IV, molecular targeted therapies are available. The study situation and approval status are dealt with in detail. With improved molecular characterization of tumors the treatment can be further individualized.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/secundário , Neoplasias Retais/cirurgia , Humanos , Terapia de Alvo Molecular , Terapia Neoadjuvante , Metástase Neoplásica , Medicina de Precisão , Qualidade de Vida , Resultado do Tratamento
9.
Int J Nanomedicine ; 15: 3563-3576, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547014

RESUMO

Background: LA67 is a derivative of triptolide that exhibits strong antitumor activity. This derivative has a better safety profile than triptolide, but is limited by poor aqueous solubility. Aim and Methods: To improve solubility and further increase therapeutic efficacy, we prepared LA67-loaded polymeric micelles (LA67-PMs) using a film hydration method. The physicochemical properties of LA67-PMs were investigated, and the antitumor activity of this formulation against Colon26 (C26) cancer cell line was evaluated in vitro and in vivo with LA67 as a control. Results: Polymeric micelles containing LA67 had a particle size of 17.88 nm and a drug entrapment efficiency of 94.84%. This formulation dispersed completely in aqueous solution and exhibited slow, sustained release of LA67. Cellular uptake assay showed that LA67-PMs delivered LA67 to cancer cells with greater efficiency than free LA67, which resulted in increased LA67 accumulation in cancer cells. Cell counting kit 8 (CCK-8) assay showed that blank polymeric micelles (PMs) exhibited low toxicity and LA67-PMs exerted pronounced anti-proliferation effects against C26 cells. Furthermore, LA67-PMs induced apoptosis and repressed migration more effectively than free LA67. In vivo evaluation of antitumor activity showed that LA67-PMs inhibited tumor growth and distant organ metastasis to a greater extent than LA67, which resulted in improved survival rate. The potential mechanisms of these effects may have been induction of apoptosis, inhibition of cell proliferation, and neovascularization. Conclusion: Our study showed that LA67-PMs may be a promising formulation for treatment of colon cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Micelas , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/irrigação sanguínea , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Tamanho da Partícula , Solubilidade , Análise de Sobrevida
10.
Cancer Immunol Immunother ; 69(10): 2009-2020, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32399587

RESUMO

OBJECTIVE: The subset distribution and immunophenotype of circulating immune cells ("peripheral blood immune cell profile") may reflect tumor development and response to cancer treatment. In order to use the peripheral blood immune cell profile as biomarker to monitor patients over time, it is crucial to know how immune cell subsets respond to therapeutic interventions. In this study, we investigated the effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma (CC). METHODS: The subset distribution and immunophenotype of T cells (CD3+CD56-), CD56dim NK cells (CD3-CD56dim), CD56bright NK cells (CD3-CD56bright) and NKT-like cells (CD3+CD56+) were studied in preoperative and postoperative peripheral blood mononuclear cell (PBMC) samples of 24 patients with CC by multiparameter flow cytometry. Changes in immunophenotype of circulating immune cells after tumor resection were studied in patients treated with and without (capecitabine-based) adjuvant therapy. RESULTS: The NKT-like cell (% of total PBMCs) and CD8+ T cell (% of total T cells) populations expanded in the peripheral blood of non-adjuvant-treated CC patients after surgery. NK- and NKT-like cells showed upregulation of activating receptors and downregulation of inhibitory receptors in non-adjuvant-treated CC patients after surgery. These changes were not observed in the peripheral blood of adjuvant-treated CC patients. CONCLUSIONS: Our results suggest tumor-induced suppression of NK- and NKT-like cells in CC patients, an effect that could not be detected after tumor resection. In contrast, adjuvant therapy maintained tumor-induced immunosuppression of NK- and NKT-like cells in CC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Neoplasias do Colo/imunologia , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo CD3 , Estudos de Casos e Controles , Quimioterapia Adjuvante , Neoplasias do Colo/sangue , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Seguimentos , Humanos , Imunofenotipagem , Células Matadoras Naturais/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Prognóstico , Linfócitos T/efeitos dos fármacos
11.
Gan To Kagaku Ryoho ; 47(4): 640-642, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32389969

RESUMO

A woman in her 50s received a detailed examination for her abdominal pain. CT indicated intestinal wall thickening of the ascending colon, lymphadenopathy, and tumor embolism in the superior mesenteric vein. Colonoscopy revealed type 2 tumor in the hepatic flexure of the colon, and she was diagnosed as having moderately differentiated adenocarcinoma by biopsy specimen. She received 12 courses of FOLFOXIRI plus BV therapy after ileostomy. As the tumor embolism disappeared and the primary lesion shrank after chemotherapy, right hemicolectomy and lymph node dissection were performed. Six months after surgery, she has had no recurrent disease. This case suggests that FOLFOXIRI plus BV therapy could be an effective treatment for right colon cancer with tumor embolism.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo , Células Neoplásicas Circulantes , Colectomia , Colo Ascendente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Feminino , Humanos , Veias Mesentéricas , Pessoa de Meia-Idade
12.
J Cancer Res Ther ; 16(1): 167-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362630

RESUMO

Lymphoproliferative malignancies can involve both nodal- and extra-nodal tissues. The most common extranodal site involved is the gastrointestinal (GI) tract, and it is secondary to the widespread primary nodal disease. However, about 33% of non-Hodgkin's lymphoma primarily arise from tissues other than lymph nodes, spleen, or bone marrow, for example, GI tract, skin, or the central nervous system and are called primary extranodal lymphomas. The most common site of GI localization is stomach (50%-60%) followed by small bowel. Primary colonic lymphoma is seen only in 6% of GI lymphomas and up to 0.5%-1% of all colon malignancies. Hence, primary GI lymphoma is extremely rare, and primary colonic lymphoma is an even rarer occurrence. There is clearly a paucity of cases reported in literature resulting in unclear treatment protocol. Here, we report a case of a 51-year-old man who presented with abdominal pain, weight loss, and bright red blood per rectum. A colonoscopy revealed diffuse bleeding ulcers involving the entire colon. Pathology was consistent with primary diffuse large B-cell lymphoma arising from the colon. The patient was started on treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone.


Assuntos
Neoplasias do Colo/virologia , Infecções por Vírus Epstein-Barr/complicações , Hemorragia Gastrointestinal/virologia , Herpesvirus Humano 4/isolamento & purificação , Linfoma Difuso de Grandes Células B/virologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Infecções por Vírus Epstein-Barr/virologia , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/patologia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prognóstico
13.
Nat Med ; 26(6): 919-931, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32451498

RESUMO

The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (TFH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of TFH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of TFH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1+ TFH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Microbioma Gastrointestinal/imunologia , Íleo/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Oxaliplatina/farmacologia , Adenocarcinoma/imunologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/uso terapêutico , Apoptose/imunologia , Bacteroides fragilis , Linhagem Celular Tumoral , Neoplasias do Colo/imunologia , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/patologia , Feminino , Firmicutes , Microbioma Gastrointestinal/fisiologia , Humanos , Íleo/imunologia , Íleo/microbiologia , Íleo/patologia , Morte Celular Imunogênica/efeitos dos fármacos , Morte Celular Imunogênica/imunologia , Vigilância Imunológica/efeitos dos fármacos , Vigilância Imunológica/imunologia , Interleucina-12/imunologia , Mucosa Intestinal , Linfócitos do Interstício Tumoral/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores Tipo I de Interleucina-1/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia
14.
Gan To Kagaku Ryoho ; 47(2): 271-273, 2020 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-32381962

RESUMO

A 73-year-old woman presenting with weight loss was diagnosed as having ascending colon cancer with synchronous liver metastasis. The liver metastasis was solitary but it occupied the medial and anterior segments. The size was over 9 cm in diameter and was located adjacent to the left, middle, and right hepatic veins, making it initially unresectable. Following surgical resection of the primary tumor, she received mFOLFOX6 plus bevacizumab chemotherapy, resulting in a decrease in size of the liver metastasis. During the 15 courses of chemotherapy, an allergic reaction to oxaliplatin occurred and oxaliplatin administration was stopped. Although the liver metastasis was considered to be in a stable disease state according to the RECIST criteria at the time following 32 courses of chemotherapy, we discontinued chemotherapy due to various reasons of the patient. However, the liver metastasis continues to be in the stable disease state, and has not grown for over 5 years since initiating mFOLFOX6 plus bevacizumab chemotherapy and for over 3 years since discontinuing the chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colo Ascendente , Neoplasias do Colo/tratamento farmacológico , Neoplasias Hepáticas , Idoso , Feminino , Fluoruracila , Humanos , Leucovorina , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Compostos Organoplatínicos , Fatores de Tempo
15.
Gan To Kagaku Ryoho ; 47(2): 298-300, 2020 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-32381968

RESUMO

A 71-year-old woman with advanced ascending colon cancer was admitted to our hospital. Abdominal computed tomography( CT)revealed locally advanced sigmoid colon cancer with suspected invasion of the liver and duodenum. The clinical stage of the disease was cT4bN3M1a, cStage Ⅳa, with wild-type RAS and UGT1A1 expression. An ileostomy was performed because of bowel obstruction. The patient received 6 courses of FOLFOXIRI plus bevacizumab(Bev). The only adverse event was Grade 3 neutropenia. Laparoscopic right hemicolectomy with lymph node dissection was performed. The pathological diagnosis was the absence of viable, Grade 3 carcinoma cells. This result suggested that preoperative FOLFOXIRI plus Bev chemotherapy is useful for the treatment of locally advanced colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colo Ascendente , Neoplasias do Colo , Idoso , Bevacizumab , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Duodeno , Feminino , Fluoruracila , Humanos , Leucovorina , Fígado , Compostos Organoplatínicos
16.
PLoS One ; 15(5): e0231948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369483

RESUMO

In our search for bioactive mushrooms native to British Columbia, we determined that the ethanol extracts from fruiting bodies of the terrestrial polypore Albatrellus flettii had potent anti-cell viability activity. Using bioassay-guided fractionation, mass spectrometry and nuclear magnetic resonance, we successfully isolated three known compounds (grifolin, neogrifolin and confluentin). These compounds represent the major anti-cell viability components from the ethanol extracts of A. flettii. We also identified a novel biological activity for these compounds, specifically in down-regulating KRAS expression in two human colon cancer cell lines. Relatively little is known about the anti-cell viability activity and mechanism of action of confluentin. For the first time, we show the ability of confluentin to induce apoptosis and arrest the cell cycle at the G2/M phase in SW480 human colon cancer cells. The oncogenic insulin-like growth factor 2 mRNA-binding protein 1 (IMP1) has been previously shown to regulate KRAS mRNA expression in colon cancer cells, possibly through its ability to bind to the KRAS transcript. Using a fluorescence polarization assay, we show that confluentin dose-dependently inhibits the physical interaction between KRAS RNA and full-length IMP1. The inhibition also occurs with truncated IMP1 containing the KH1 to KH4 domain (KH1to4 IMP1), but not with the di-domain KH3 and KH4 (KH3&4 IMP1). In addition, unlike the control antibiotic neomycin, grifolin, neogrifolin and confluentin do not bind to KRAS RNA. These results suggest that confluentin inhibits IMP1-KRAS RNA interaction by binding to the KH1&2 di-domains of IMP1. Since the molecular interaction between IMP1 and its target RNAs is a pre-requisite for the oncogenic function of IMP1, confluentin should be further explored as a potential inhibitor of IMP1 in vivo.


Assuntos
Basidiomycota/química , Neoplasias do Colo/genética , Fenóis/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Resorcinóis/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Terpenos/farmacologia
17.
Int J Nanomedicine ; 15: 2873-2884, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368059

RESUMO

Purpose: The primary goal of the present study was to design doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (NPs) coated with mesenchymal stem cell (MSC) membranes and explore their effect on colon cancer in vitro and in vivo. Methods: DOX-SPIO NPs were coated with MSC membranes using an extruder, and the morphological characteristics of MSC membrane-camouflaged nanodrug (DOX-SPIO@MSCs) evaluated by transmission electron microscopy (TEM) and NP-tracking analysis. Drug loading and pH response were assessed by UV spectrophotometry. Intracellular colocalization was analyzed using NP-treated MC38 cells stained with 3,3'-dioctadecyloxacarbocyanine perchlorate and Hoechst 33342. Cellular uptake was analyzed using an inverted fluorescence microscope and flow cytometry and cytotoxicity evaluated by cell counting kit-8 assay. Biological compatibility was assessed by hemolysis analysis, immunoactivation test and leukocyte uptake experiments. Furthermore, intravenous injection of chemotherapy drugs into MC38 tumor-bearing C57BL/6 mice was used to study anti-tumor effects. Results: Typical core-shell NP structures were observed by TEM. Particle size remained stable in fetal bovine serum and phosphate-buffered saline (PBS). Compared with DOX-SPIO, DOX-SPIO@MSCs improved cellular uptake efficiency, enhanced anti-tumor effects, and reduced the immune system response. Animal experiments demonstrated that DOX-SPIO@MSCs enhanced tumor treatment efficacy while reducing systemic side effects. Conclusion: Our experimental results demonstrate that DOX-SPIO@MSCs are a promising targeted nanocarrier for application in treatment of colon cancer.


Assuntos
Membrana Celular/transplante , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Células-Tronco Mesenquimais/citologia , Nanopartículas/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Compostos Férricos/química , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Nanopartículas/administração & dosagem , Tamanho da Partícula , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1174-1179, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237462

RESUMO

In order to explore the characteristics of traditional Chinese medicine(TCM) syndromes and medications in patients with colonic malignant tumors in China, the clinical data of patients with colonic malignant tumors from the information system of 33 Grade-A tertiary hospitals in China from 2001 to 2016 were extracted and a descriptive analysis was conducted on their disease characteristics, syndrome distribution, drug characteristics and treatment status. A total of 22 691 patients with colonic malignancies nationwide were included in the analysis, with male to female ratio of 1.59∶1, median age of 62 years, susceptible age of 50-79 years. Postoperative patients with colonic malignant tumors accounted for 47.10%, and patients with liver metastases reached 36.02%. Among the 520 patients with colonic malignant tumors, the top three TCM syndromes were: spleen deficiency syndrome(21%), Qi and Yin deficiency syndrome(17%) and liver and stomach disharmony syndrome(15%). The most frequently used Western medicine for patients with colonic malignant tumors was anti-metabolite cytotoxicity(61.23%), most frequently used in combination with platinum-based cytotoxic drugs(support degree 42.40%).The top three Western medicines were oxaliplatin(42.26%), leucovorin injection(38.58%) and dexamethasone(34.67%). The most frequently used traditional Chinese medicine type was heat-clearing and detoxifying drugs(39.59%), most frequently used in combination with Qi replenishing and body resistance strengthening drugs(support degree 12.72%). The top three traditional Chinese medicines were compound Kushen Injection(14.62%), Shenqi Fuzheng Injection(10.18%) and Aidi Injection(6.48%). This study shows that spleen and Qi deficiency may be the dominant syndrome of colonic malignant tumor, and chemotherapy is one of the main treatment methods. Traditional Chinese medicine has shown unique advantages in alleviating the toxic and side effects of chemotherapy and preventing recurrence and metastasis, so integrated TCM and Western medicine can significantly improve the clinical efficacy.


Assuntos
Neoplasias do Colo/diagnóstico , Neoplasias do Colo/tratamento farmacológico , Medicina Tradicional Chinesa , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência da Energia Yin
19.
Mar Drugs ; 18(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344610

RESUMO

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.


Assuntos
Antineoplásicos/administração & dosagem , Quitosana/química , Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Sinvastatina/administração & dosagem , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Portadores de Fármacos/química , Células HCT116 , Humanos , Concentração de Íons de Hidrogênio , Masculino , Microesferas , Tamanho da Partícula , Ácidos Polimetacrílicos/química , Coelhos , Sinvastatina/farmacologia
20.
J Surg Oncol ; 121(8): 1298-1305, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32239529

RESUMO

BACKGROUND: Peritoneal carcinomatosis of colorectal adenocarcinoma (CRC) origin is common and is the second-most frequent cause of death in colorectal cancer. There is survival benefit to surgical resection plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with metastatic CRC. However, there remains controversy between oxaliplatin (Oxali) and mitomycin C (MMC), as the agent of choice. METHODS: A review of our 285 patients prospective HIPEC database from July 2007 to May 2018 identified 48 patients who underwent cytoreductive surgery plus HIPEC with MMC or Oxali. Patients were stratified based on preoperative and postoperative peritoneal cancer indices (PCI). The primary outcomes of survival and progression-free survival were compared. RESULTS: Type of HIPEC chemotherapy was not found to be predictive of overall survival. Preoperative PCI (P = .04), preoperative response to chemotherapy (P = .0001), and postoperative PCI (P = .05) were predictive for overall survival. CONCLUSIONS: MMC or Oxali based HIPEC chemotherapy are both safe and effective for the management of peritoneal only metastatic CRC. Both perfusion therapies should be considered with all patients receiving modern induction chemotherapy.


Assuntos
Neoplasias do Colo/terapia , Hipertermia Induzida/métodos , Mitomicina/administração & dosagem , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/terapia , Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Estudos Prospectivos , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA