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1.
Pan Afr Med J ; 33: 161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565123

RESUMO

We present a histologically proven mucinous adenocarcinoma of the colon in a 40 year old female from Gulu, Northern Uganda. Her elder sister died at 25 years with advanced adenocarcinoma of colon similarly with her mother who died of the same illness 10 years apart. Using the Amsterdam criteria for the diagnosis of the carcinoma of the colon, this is descriptive of Hereditary Non Polyposis Colorectal Carcinoma (HNPCC). Blood examinations revealed microcytic hypochromic anaemia. The Renal and Liver function parameters were essentially normal. The abdominal ultrasonography showed an ill-defined mass in the right hypochondrial region which was heterogeneous with central echogenicity approximately 7.2cm wide and with no intra-abdominal lymphadenopathy or ascitis. At laparotomy, the sonographic findings were confirmed with a demonstrable mass in the hepatic flexure of the colon with hyperemic areas on its serosa. Macroscopically, there was an annular fungating mass with a central necrosis in the hepatic flexure measuring over 7.0cm. Histology of the colonic tumour showed a mucinous adenocarcinoma of the colon (Duke's B). This finding highlights the occurrence of colonic adenocarcinoma in the young person in Northern Uganda, a finding which draws the attention of the medical community towards having a higher index of suspicion for carcinoma of the colon in patients with similar presentation.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Anemia Hipocrômica/diagnóstico , Neoplasias do Colo/diagnóstico , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Laparotomia/métodos , Uganda
2.
Anticancer Res ; 39(10): 5645-5652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570462

RESUMO

BACKGROUND/AIM: The aim of our study was to assess the predictive role of primary tumour sidedness (PTS) in patients with metastatic colorectal cancer (mCRC) harbouring wild-type RAS and treated with targeted agents. PATIENTS AND METHODS: The cohort included 178 patients treated with first-line chemotherapy plus cetuximab, panitumumab or bevacizumab. RESULTS: We observed longer progression-free survival (PFS) and overall survival (OS) in patients with left-sided (L-CRC) compared to right-sided tumours (R-CRC) treated with anti-EGFR mAbs (p=0.0033 and p=0.0037), while there was no difference in patients treated with bevacizumab (p=0.076 and p=0.56). Finally, we observed longer PFS and OS in patients with L-CRC treated with anti-EGFR mAbs and those with R-CRC treated with bevacizumab compared to the reverse combination (p=0.0002 and p=0.011). CONCLUSION: PTS is a predictive factor for anti-EGFR mAbs, not for bevacizumab. Superior survival was observed when anti-EGFR mAbs were used for L-CRC and bevacizumab for R-CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Idoso , Anticorpos Monoclonais/administração & dosagem , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Genes ras/genética , Humanos , Masculino , Panitumumabe/administração & dosagem
3.
Gan To Kagaku Ryoho ; 46(8): 1319-1321, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501379

RESUMO

A66 -year-old man was diagnosed with chronic myeloid leukemia(CML). Imatinib treatment had been initiated, and a major molecular response(MMR)was achieved. The patient had anemia and was diagnosed with descending colon cancer. The patient was surgically treated, and then received postoperative adjuvant chemotherapy with UFT/LV. However, imatinib was not administered during that period. The patient could undergo postoperative adjuvant chemotherapy for 6 months without acute exacerbation of the CML.


Assuntos
Neoplasias do Colo , Leucemia Mielogênica Crônica BCR-ABL Positiva , Idoso , Antineoplásicos , Quimioterapia Adjuvante , Colo Descendente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Masculino , Resultado do Tratamento
4.
Gan To Kagaku Ryoho ; 46(8): 1327-1329, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501381

RESUMO

BACKGROUND: This study was designed to clarify effects of postoperative adjuvant chemotherapy for high-risk Stage Ⅱ colorectal cancer. METHOD: The subjects were 99 patients with high-risk Stage Ⅱcolorectal cancer who underwent surgery at our department from October 2013 to March 2018. Patients were classified into adjuvant chemotherapy group and nonadjuvant chemotherapy group. Overall survival(OS)and recurrence-free survival(RFS)were analyzed between the 2 groups. RESULTS: Thirty six patients(36.4%)underwent adjuvant chemotherapy. Adjuvant chemotherapy group were younger(p<0.010), had a better ASA-PS(p<0.010), good preoperative Hb(p<0.010), and preoperative Alb(p<0.010)compared to non-adjuvant chemotherapy group. There was no difference between the 2 groups in the high-risk factors for recurrence. Most patient had an oral medication as for adjuvant chemotherapy. There was no difference in OS and RFS between the 2 groups. CONCLUSION: Postoperative adjuvant chemotherapy for high-risk Stage Ⅱ colorectal cancer did not significantly improve the OS and RFS. Further study is necessary to asses the suitable regimen and patients eligible for chemotherapy.


Assuntos
Neoplasias do Colo , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias
5.
Gan To Kagaku Ryoho ; 46(8): 1330-1333, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501382

RESUMO

BACKGROUND: T4 is one of the high-risk factors, but the efficacy of adjuvant chemotherapy for T4-Stage Ⅱ colon cancer are unclear. METHOD: We retrospectively reviewed 211 patients with primary pStage Ⅱ colon cancer who underwent radical resection between 2004 and 2015. RESULTS: The 5-year overall survival rate(OS)of Stage ⅡA/ⅡB/ⅡC were 90.2/83.4/ 59.2%, and the 5-year recurrence-free survival rate(RFS)were 87.3/73.3/42.8%. Multivariate analysis of OS as a high-risk factor of T4 revealed male, ly2/3, no adjuvant chemotherapy, and in RFS, male, ly2/3. However, compared the cases with or without adjuvant chemotherapy, 5-year OS was no difference. There were no cases used oxaliplatin-based adjuvant chemotherapy. CONCLUSION: An adjuvant chemotherapy without oxaliplatin were not enough to improve the prognoses of T4-Stage Ⅱcolon cancer, so the oxaliplatin based regimen might be recommended.


Assuntos
Neoplasias do Colo , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Humanos , Masculino , Estadiamento de Neoplasias , Compostos Organoplatínicos , Estudos Retrospectivos , Fatores de Risco
6.
Medicine (Baltimore) ; 98(36): e16995, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490381

RESUMO

RATIONALE: Active tuberculosis constitutes a relevant risk for kidney transplant recipients. In contrast to immunocompetent hosts, kidney transplant recipients often show atypical presentation and course of the disease impeding diagnosis. Especially extrapulmonary or disseminated infection is more frequent and can resemble malignant processes. However, reactivation of tuberculosis mostly develops within the early post-transplant course, whereas malignancies are predominantly long-term complications. We report a case of disseminated abdominal tuberculosis developing 10 years after kidney transplantation and review the underlying literature. PATIENT CONCERNS AND DIAGNOSES: A 51-year-old lady presented with epigastric pain, diarrhea, weight loss and night sweats 10 years after deceased-donor kidney transplantation. An epigastric as well as multiple peritoneal masses were found suspicious of a cancer of unknown primary. Colonoscopy revealed a colon tumor with the biopsy showing no dysplasia but histiocytic and granulomatous infiltration with acid-fast bacilli. Mycobacterium tuberculosis was detected in the biopsy and stool and disseminated abdominal tuberculosi was diagnosed. INTERVENTIONS AND OUTCOMES: With anti-tuberculosis therapy, the masses regressed, and all cultures became sterile, sparing graft function. LESSONS: This case emphasizes how variable and unspecific the presentation of tuberculosis in kidney transplant recipients may be and that tuberculosis constitutes a relevant risk also in the long-term post-transplant course.


Assuntos
Neoplasias do Colo/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Tuberculose Gastrointestinal/diagnóstico , Antituberculosos/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Transplante de Rim , Pessoa de Meia-Idade , Tuberculose Gastrointestinal/tratamento farmacológico
7.
Rev Inst Med Trop Sao Paulo ; 61: e49, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531627

RESUMO

This manuscript reports a case of intestinal toxemia botulism in an adult with recently diagnosed metastatic colon cancer in whom botulism symptoms began 23 days after hospital admission. Representing the rarest form of botulism presentation in clinical practice, this infectious disease may have developed due to a cluster of predisposing factors that favored Clostridium botulinum colonization and the endogenous production of neurotoxins, among which are previous use of broad-spectrum antibiotics and colon changes related to the development of the neoplasia. This case highlights the importance of considering intestinal toxemia botulism in the differential diagnosis of a patient presenting with symmetrical descending flaccid paralysis, since immediate treatment with botulinum antitoxin may improve clinical outcomes.


Assuntos
Botulismo/diagnóstico , Neoplasias do Colo/complicações , Infecção Hospitalar/microbiologia , Enteropatias/microbiologia , Toxemia/diagnóstico , Botulismo/complicações , Evolução Fatal , Fezes/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Toxemia/complicações
8.
Anticancer Res ; 39(9): 4965-4970, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519602

RESUMO

BACKGROUND/AIM: Colonic crypts with normal epithelium albeit with corrupted shapes (CCS) were previously found beneath nonpolypoid adenomas (NPA). This study aimed to analyze the distribution of proliferating cells (PC) and p53-up-regulated cells in CCS. MATERIALS AND METHODS: Sections from 48 NPA were immunostained with the proliferating-marker Ki67 and against the tumor-suppressor protein p53. RESULTS: Asymmetric-haphazardly distributed PC were found in 87.5% of the NPA, continuous PC-domains in 8.3%, asymmetric-haphazardly distributed single PC in 4.2% and p53-up-regulated cells in 29.2%. In 12 controls, the normal-shaped crypts revealed symmetrically-distributed PC-domains in their lower thirds, and no p53-up-regulated cells. CONCLUSION: The normal epithelium that lines the CCS below NPA, thrives with relocated PC-domains, and with occasional p53-up-regulated cells. These findings strongly suggest that the normal epithelium of CCS beneath NPA might harbor somatic mutations. The accretion of putative mutated CCS might play an important role in the evolution of nonpolypoid adenomas in the human colon.


Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Mucosa Intestinal/metabolismo , Proteína Supressora de Tumor p53/genética , Adenoma/metabolismo , Adenoma/patologia , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Fenótipo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
9.
Khirurgiia (Mosk) ; (8. Vyp. 2): 65-69, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31502596

RESUMO

Laparoscopic colon resections are currently becoming a standart method of surgical treatment of colon cancer. Long-term oncologic outcomes of such procedures are shown to be non-inferior to outcomes of traditional open surgery, while short-term results and morbidity profile are more favourable. The current direction of colon mini-invasive surgery development is to make procedures more easily tolerable by patients, using less traumatic methods and operative approaches. The article contains a review of one of such methods, which allows less traumatic performance of laparoscopic right hemicolectomy - an intracorporeal ileotransversoanastomosis. The current evidence concerning safety and efficacy are reviewed, when authors' own data are also brought to support implementation of this method into routine practice.


Assuntos
Colectomia/métodos , Colo Transverso/cirurgia , Neoplasias do Colo/cirurgia , Íleo/cirurgia , Anastomose Cirúrgica/métodos , Humanos , Laparoscopia , Resultado do Tratamento
10.
Rev Col Bras Cir ; 46(3): e20192098, 2019 Aug 15.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31432981

RESUMO

OBJECTIVE: to evaluate the clinical and pathological differences between locally advanced colonic adenocarcinomas (LACA) with adhesions between adjacent organs or structures, and colonic adenocarcinomas with other clinical presentations. METHODS: we conducted a retrospective study from a convenience sample of patients with colonic adenocarcinoma, pathological stage pT3, distributed according to clinical and pathological characteristics in three groups: locally advanced tumors (LACA), pT3 tumors without adhesions or distant metastases (SF) and tumors with metastatic disease (M1). We evaluated clinical and pathological characteristics and the expression of seven immunohistochemical markers related to proliferation/apoptosis, cell invasion/migration and metastasis. RESULTS: we studied 101 patients: 30 LACA, 44 SF and 27 M1. Locally advanced tumors presented larger dimensions and were associated with increased lymphocyte infiltration rates, lower levels of bax expression, and CD 44v6 when compared with SF and M1 groups. We observed significant differences between LACA and M1 in relation to colonic location, histology, lymph node status and bax and CD44v6 expression. We found differences were observed between the three groups for tumor size and lymphocytic infiltrate. Survival was similar in the LACA and SF groups (p=0.66) and was lower in the M1 group (p<0.001). CONCLUSION: the data suggest that locally advanced colonic adenocarcinomas with adhesions between adjacent organs or structures represent a distinct entity.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Adenocarcinoma/mortalidade , Neoplasias do Colo/mortalidade , Humanos , Imuno-Histoquímica , Estudos Longitudinais , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida
11.
Gene ; 718: 144030, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31390540

RESUMO

Opioids are widely used in the treatment of cancer related pain. They mainly exert their effects on opioid receptors. The most common opioid in the treatment of pain is morphine. Previous studies show that they may have effects on cancer cell behavior. These may include apoptosis, angiogenesis, invasion, inflammation and immune reactions. Tramadol, also an opioid is widely used in the treatment of cancer pain and is not well studied in cancer behavior. We aimed to investigate the effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells. We used Colo320 (ATCC, CCL-220), Colo741 (ECACC, 93052621) and HCT116 (ATCC, CCL-247) colon cancer cell lines. CD133 was considered colon cancer stem cell marker and used to sort CD133+ and CD133- cells by magnetic cell sorting. MTT (mitochondria-targeted therapeutics) technique was used to detect tramadol's cytotoxic effect on cells in the study groups. Cells were treated with 1 mg/kg, 1.5 mg/kg and 2 mg/kg tramadol for 24 h at 37 °C and 5% CO2.Caspase-3, Ki-67, Bcl-2 and VGEF distributions were performed using indirect immunoperoxidase staining for immunohistochemical analysis. The study showed that tramadol has triggering effect on apoptosis in Colo320 colon cancer stem cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo , Citotoxinas/farmacologia , Células-Tronco Neoplásicas , Tramadol/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células HCT116 , Humanos , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
12.
Anticancer Res ; 39(8): 4065-4071, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366489

RESUMO

BACKGROUND: Surgical orthotopic implantation of human colon cancer tissue to the ceca of mice has been used to mimic behavior of cancer in human patients for the development of precision cancer medicine. However, with the current method of serosal surface implantation (SSI) of pieces of human colon cancer tissue, cancer cells are exposed to the peritoneum, which can artificially increase the rate of peritoneal carcinomatosis (PC) during the disease course. The objective of the present study was to introduce a tumor-sealing method (TSM) and compare it with SSI for the ability to produce clinically-relevant metastases without artificial PC. MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm3-sized tumor fragment was sutured to partially torn serosa of the cecum. For TSM, the blind end of the cecum was folded over the tumor fragment and sealed with sutures. At 20 days after implantation, all mice were opened to visualize PC by intravital fluorescence imaging. At necropsy, distant metastasis was investigated using frozen section of whole blocks of organs. RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001). CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.


Assuntos
Carcinogênese/genética , Neoplasias do Colo/patologia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/química , Células HCT116 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos , Metástase Neoplásica , Transplante de Neoplasias/métodos , Imagem Óptica , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Anticancer Res ; 39(8): 4259-4263, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366515

RESUMO

BACKGROUND/AIM: Sessile serrated polyps (SSP) are characterized by crypts with corrupted shapes (CCS). MATERIALS AND METHODS: The number of CCS and the lateral size of 60 non-dysplastic SSP (NDSSP) were investigated. RESULTS: Out of 60 NDSSP, 34 were small (≤9 mm) and 26, large (≥10 mm). In total, 1,101 CCS were recorded: 547 CCS were connected to the lumen (CCSL) and 554 CCS were not (CCSNL). The lateral size of NDSSP, the total number of CCS and the number of CCSNL were significantly higher in large NDSSP than in small NDSSP. Conversely, the number of CCS connected to the lumen/mm (CCSL/mm) and of crypts with normal shapes connected to the lumen/mm (CCSNL/mm), were significantly lower in large NDSSP than in small NDSSP. CONCLUSION: The lateral expansion of large NDSSP ensues via increased numbers of CCS at the expense of a decreased number of both CCSL/mm and CCSNL/mm.


Assuntos
Adenoma/fisiopatologia , Neoplasias do Colo/fisiopatologia , Pólipos do Colo/fisiopatologia , Adenoma/cirurgia , Colo/fisiopatologia , Colo/cirurgia , Neoplasias do Colo/cirurgia , Pólipos do Colo/cirurgia , Humanos
14.
Anticancer Res ; 39(8): 4405-4410, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366537

RESUMO

BACKGROUND/AIM: Recent studies have reported the involvement of NADPH oxidases (NOXs) in tumor progression. However, the role of NOX5 in colon cancer is unclear. We examined the clinical significance of NOX5 expression in colon cancer. PATIENTS AND METHODS: NOX5 expression was evaluated by immunohistochemistry in 119 patients with stage II or III colon cancer, and the relationship between NOX5 expression and clinicopathological data was analyzed. RESULTS: Of all tissues, 39.5% were negative and 60.5% were positive for NOX5 expression. Positive expression was significantly associated with undifferentiated histology (p=0.037) and lymph node metastasis (p=0.023). The 5-year progression-free survival rate of NOX5-positive patients was significantly worse than that of NOX5-negative patients (p=0.046). The rates of local recurrence observed in NOX5-positive patients were higher than that in NOX5-negative patients. CONCLUSION: NOX5 expression may be related to poor prognostic factors and could be useful as a prognostic biomarker.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias do Colo/cirurgia , NADPH Oxidase 5/genética , Recidiva Local de Neoplasia/cirurgia , Idoso , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão
15.
Zhonghua Zhong Liu Za Zhi ; 41(8): 573-579, 2019 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-31434447

RESUMO

Objective: To observe the expressions of periostin (Postn) in colon cancer tissues and cells, and to investigate its biological effect and mechanism in colon cancer cells. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of Postn, let-7a and miR-98 in 20 pairs of colon cancer tissues and adjacent normal tissues, colon cancer cell lines including SW480, HT-29, HCT-116 and human normal colon epithelial cell NCM460. Small interfering RNAs (siRNAs) of Postn, pcDNA3.1-Postn plasmids, let-7a mimic and its negative control let-7a mimic-NC, miR-98 mimic and its negative control miR-98 mimic-NC were transfected into HCT-116 cells. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Luciferase reporter gene assay was used to determine the targeting relationship between miRNAs and Postn. Results: Compared with adjacent normal tissues, Postn expression was up-regulated (P<0.05) while let-7a/miR-98 expression was down-regulated (P<0.05) in colon cancer tissues. Compared with NCM460 cells, Postn expression was up-regulated (P<0.05) while let-7a/miR-98 expression was down-regulated (P<0.05) in SW480, HT-29 and HCT-116 cells. In colon cancer tissues, the expression of Postn was negatively correlated with the expressions of let-7a and miR-98 (r=-0.69, P<0.001; r=-0.80, P<0.001). Inhibition of Postn in vitro reduced the viability of HCT-116 cells [(53.73±7.63)%, P<0.05], increased the apoptotic rate [(22.88±3.40)%, P<0.05], enhanced the expression of epithelial-mesenchymal transition (EMT) marker E-cadherin (2.44±0.39, P<0.05), while down-regulated the expressions of N-cadherin and Vimentin (0.44±0.07 and 0.38±0.06, P<0.05). Overexpression of Postn in vitro enhanced the cell viability of HCT-116 cells [(134.41±8.82) %, P<0.05], decreased the expression of E-cadherin (0.55±0.09, P<0.05), increased the expressions of N-cadherin and Vimentin (2.93±0.42 and 2.24±0.34, P<0.05), but had no effect on the apoptotic rate (P>0.05). Overexpression of let-7a or miR-98 partially reversed the biological effects of Postn overexpression in colon cancer cells, which implicated that Postn was a target gene of let-7a/miR-98. Conclusions: Postn is a cancer-promoting molecule of colon cancer, and inhibition of Postn expression can increase the apoptotic rate of colon cancer cells and repress EMT. Postn expression and function is regulated by let-7a/miR-98.


Assuntos
Moléculas de Adesão Celular/metabolismo , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Apoptose , Neoplasias do Colo/metabolismo , Transição Epitelial-Mesenquimal , Humanos , MicroRNAs/metabolismo
16.
Zhonghua Zhong Liu Za Zhi ; 41(8): 580-586, 2019 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-31434448

RESUMO

Objective: To investigate the effect of down-regulation of insulin-like growth factor 2 (IGF2) gene on the biological characteristics of HCT116 colon cancer stem cells (CSCs). Methods: Flow cytometry sorting technology was used to isolate CSCs from colon cancer cell line HCT116 by a monoclonal antibody against CD133; serum free floating culture assay was used for the enrichment of CSCs. The proportion of CD133(+) cells was analyzed by flow cytometry; CSCs were identified by sphere culturing, immunofluorescence analysis and soft agar clone formation. RT-qPCR method was used to examine transcriptional level of IGF2 gene in CSCs. Western blotting was used to examine IGF2 protein expression in CSCs. siRNA was used to establish IGF2 transient knock down model in CSCs. Cell proliferation array, cell cycle and apoptosis analysis, cell invasion array and colony forming assay were used to further examine the role of IGF2 on the biological characteristics of colon CSCs. Results: CSCs were successfully isolated from HCT116 cell lines, which were cultured to form cell spheres in serum-free stem cell culture medium. We found that the morphology of sphere-forming-like cells after several passages maintained the same characteristics as that of the first passage. The results of immunofluorescence showed that CSC markers including CD133 and ALDH continued positively expressing on the cell surface of CSCs, and flow cytometry analysis showed that more than 90% of the spheroid cells remained CD133 positive. The clone formation rate of non-CSCs group and CSCs group were (28.10±2.66)% and (43.73±2.30)% respectively, with significant difference (P<0.01). The RT-qPCR results showed that the transcriptional level IGF2 gene in non-CSCs group and CSCs group were (1.06±0.24) and (2.17±0.51) respectively, with significant difference (P<0.05). The western blot results showed that the protein expression of IGF2 in CSCs group and non-CSCs group were (1.10±0.55) and (2.14±0.23) respectively, with significant difference (P<0.05). Knockdown of IGF2 significantly decreased the percentage of CD133(+) cells in CSCs and cell proliferation (P<0.01). Knockdown of IGF2 increased the percentage of G(2)/M phase (23.46% of siNC group vs 60.14% of siIGF2 group) and cell apoptosis (2.80% of siNC group vs 40.70% of siIGF2 group), while decreased the percentage of G(0)/G(1) phase (40.77% of siNC group vs 17.73% of siIGF2 group). The invasion results showed that the number of cells penetrating into the basement surface in siNC group and siIGF2 group was (109.00±16.37) and (54.00±8.19) respectively, with significant difference (P<0.01). The rate of sphere-forming of colon CSCs in siNC group and siIGF2 group were (51.70±7.42)% and (21.27±2.35)% respectively, with significant difference (P<0.01). The clone formation rate of siNC group and siIGF2 group were (37.20±3.87)% and (18.23±2.25)% respectively, with significant difference (P<0.01). Conclusion: IGF2 gene plays an important role in maintaining the biological characteristics of colon cancer stem cells and promoting self-renewal and stemness of colon CSCs.


Assuntos
Neoplasias do Colo/genética , Regulação para Baixo , Células HCT116/fisiologia , Fator de Crescimento Insulin-Like II/genética , Células-Tronco Neoplásicas/fisiologia , Proliferação de Células , Neoplasias do Colo/fisiopatologia , Humanos , Fator de Crescimento Insulin-Like II/metabolismo
17.
Khirurgiia (Mosk) ; (8): 29-35, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31464271

RESUMO

OBJECTIVE: To compare short- and long-term outcomes of treatment in patients with colon cancer undergoing laparoscopic and open surgery. MATERIAL AND METHODS: There were 281 patients with colon cancer. All patients underwent open (n=144, 51.2%) or laparoscopic (n=137, 48.8%) procedures. Short- and long-term outcomes of treatment were compared in both groups. RESULTS: There were no significant differences in sex, age, body mass index, location of tumors and tumor differentiation grade in both groups. Conversion was required in 10 (7.2%) cases. The median of duration of surgery was greater for laparoscopic procedures (150 min vs. 130 min; p<0.001). Intraoperative blood loss was significantly less in laparoscopic surgery (100 ml vs. 300 ml; p=0.001). Postoperative mortality was similar (3.5% vs. 2.5%; p=0.5) while incidence of postoperative complications was significantly lower after laparoscopic interventions (13.1% vs. 22.2%; p=0.04). There was earlier recovery of the gastrointestinal tract after laparoscopic procedures (2.1±0.9 days vs. 3.6±1.5 days, respectively; p<0.001). The postoperative hospital-stay was significantly less in the 2nd group (p<0.001). Two-year disease -free and overall survival was similar in both groups. CONCLUSION: Laparoscopic interventions for colon cancer are followed by similar overall and disease-free 2-year survival and better early outcomes.


Assuntos
Colectomia , Neoplasias do Colo/cirurgia , Colectomia/efeitos adversos , Colectomia/métodos , Colectomia/mortalidade , Humanos , Laparoscopia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Life Sci ; 234: 116788, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445935

RESUMO

Livin is an important member of the human inhibitor of apoptosis proteins (IAPs) family. IAPs are proteins with antiapoptotic abilities, and their functions are different from the Bcl-2 (B-cell lymphoma-2) family proteins. However, the precise role of Livin in colon cancer progression remains unclear. The purpose of this study is to assess the effect of overexpression Livin in colon cancer cells and to examine its molecular mechanism. We demonstrated that Livin induced a colon cancer phenotype, including proliferation and migration, by regulating H2A.XY39ph (histone family 2A variant (H2AX) phosphorylated on the 39th serine site). We elucidated that Livin degraded Jumonji-C domain-containing 6 protein (JMJD6), which was mediated by the proteasome murine double minute 2 (MDM2), thereby regulating H2A.XY39ph. Above all, the overexpression of JMJD6 recovered H2A.XY39ph in colon cancer cells with a high level of Livin, thus inhibiting colon cancer malignancy progression. These results reveal a previously unrecognized role for Livin in regulating the tumor-initiating capacity in colon cancer and provide a novel treatment strategy in cancer via the interruption of H2A.XY39ph function and the interaction between H2A.XY39ph and JMJD6.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias do Colo/patologia , Histonas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Neoplasias/metabolismo , Mapas de Interação de Proteínas , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Humanos , Proteínas Inibidoras de Apoptose/genética , Histona Desmetilases com o Domínio Jumonji/genética , Proteínas de Neoplasias/genética , Proteólise
20.
Medicine (Baltimore) ; 98(35): e16919, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464927

RESUMO

Antiangiogenic therapy has shown clinical benefit in metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of apatinib in patients who failed standard treatment and to explore potential factors related to its efficacy.A total of 47 patients were enrolled in this retrospective study. Patients who received apatinib therapy after failure of standard therapy from December 2014 and February 2018 were included. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events were recorded and evaluated.The median PFS was 3.717 months (95% confidence interval [CI], 3.198-4.235), and the median OS was 7.335 months (95% CI, 6.738-7.932). The disease control rate was 72.34%, and the ORR was 8.51%. The most common grade 3 to 4 adverse reactions were hypertension, proteinuria, hand-foot syndrome, and diarrhea. Multivariate analysis indicated previous antiangiogenic therapy and baseline elevated neutrophil-to-lymphocyte ratio (NLR) as independent prognostic factors.Apatinib might be a reasonable treatment option with a controlled safety profile for patients with mCRC who have failed standard therapy. Patients who previously received antiangiogenic therapy and who have baseline elevated NLR are more likely to benefit from apatinib.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Análise Multivariada , Prognóstico , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
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