RESUMO
BACKGROUND: The Notch signaling mutation is associated with enhanced anti-tumor immune response in colorectal cancer (CRC). In this study, we aim to investigate the underlying mechanism and the predictive potential of Notch signaling mutation for responding to immunotherapy in CRC. METHODS: We analyzed the immune response associated genes in CRC with Notch signaling mutation concomitant with or without microsatellite instability (MSI) using TCGA dataset and investigated the mutation profiles of the Notch signaling pathway using cBioPortal. The Notch signaling scores and immune cell infiltration scores in different groups were calculated. We applied the Kaplan-Meier method for survival analysis in CRC patients who underwent immunotherapy, and the log-rank test to determine the statistically significant differences in survival. Notch1-knock-down cell line was constructed to detect the pathway and gene variations. RESULTS: We found that Notch signaling pathway mutation was associated with activated immune response, especially in those with MSI. Such association is useful for predicting a prolonged overall survival of CRC patients who underwent immune checkpoint inhibitor treatment. The mutation resulted in the functional loss of Notch signaling and may modulate the tumor immune microenvironment by increasing the expression of chemokines that are important for recruiting immune cells. CONCLUSIONS: The Notch signaling mutation can modulate the chemotaxis of immune cells by upregulating the chemokine levels of the tumor immune microenvironment, and CRC patients with Notch signaling pathway mutation have better overall survival after immune checkpoint inhibitor treatment.
Assuntos
Neoplasias Colorretais , Quimiocinas/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Instabilidade de Microssatélites , Mutação , Prognóstico , Transdução de Sinais/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.
Assuntos
Fibrinogênio/análise , Gastrectomia , Pontuação de Propensão , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND AND AIMS: Abdominal cocoon (AC) is a rare abdominal disease with nonspecific clinical features, and it is difficult to be diagnosed before operation and hard to be treated in clinical practice. The aim of this study is to investigate the diagnosis and treatment of AC. METHODS: The clinical manifestations, findings during surgery, treatments, and follow-up results of 26 cases of AC were retrospectively studied from January 2001 to January 2015. RESULTS: All of 26 cases were diagnosed as AC definitely by laparotomy or laparoscopic surgery. Their clinical findings were various, with 7 intestines obstructed with bezoars and 4 intestines perforated by spiny material. Based on the existence of the second enterocoelia, all cases were categorized into 2 types: type I is absent of second enterocoelia (18 cases, 69.23%), while type II shows second enterocoelia (8 cases, 30.77%). Twenty cases (12 were type I and 8 were type II) underwent membrane excision and careful enterodialysis to release the small intestine entirely or partially, while the other 6 cases (all were type I) did not. In addition, all patients were treated with medical treatment and healthy diet and lifestyle. Finally, most of the patients recovered smoothly. CONCLUSIONS: AC can be categorized into two types; surgery is recommended for type II and part of type I with severe complications, but sometimes conservative therapy might be appropriate for type I. Laparoscopic surgery plays an important role in the diagnosis and treatment of AC. Furthermore, favorite health education, healthy diet and lifestyle are of significance in patients' recovery.
Assuntos
Fibrose Peritoneal/diagnóstico , Fibrose Peritoneal/cirurgia , Adolescente , Adulto , Idoso , Tratamento Conservador , Feminino , Humanos , Laparoscopia , Laparotomia , Masculino , Pessoa de Meia-Idade , Fibrose Peritoneal/classificação , Fibrose Peritoneal/etiologia , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The co-stimulatory molecule B7-H3 plays an important role in prognosis of several malignancies. However, its prognostic value in clinic in patient with colorectal cancer (CRC) is still controversial. This meta-analysis evaluated the relationship between B7-H3 expression and the outcomes of CRC patients. METHODS: PubMed, Google Scholar, Embase, CNKI and Wanfang database were searched for the studies on the relationship between the expression of B7-H3 and prognosis of CRC patients. Pooled odds ratios (ORs) analysis with 95% confidence interval (95% CIs) for lymph node metastasis, 24-month overall survival and 72-month overall survival were performed mainly using Review Manager 5.0. RESULTS: Six articles including 1,202 total CRC cases were included for the meta-analysis. Pooled analysis with fixed-effects model showed that B7-H3 expression had no relationship with lymphatic metastasis in CRC patients (Fixed-effects, OR= 1.18; 95 % CI:0.87-1.61, P=0.28). However, B7-H3 expression was associated with 24-month overall survival (Fixed-effects, OR=0.48, 95% CI:0.32-0.74, P<0.001) and 72-month overall survival (Fixed-effects, OR = 0.61, 95% CI: 0.43-0.85, P< 0.01) in CRC patients. CONCLUSION: The co-stimulatory molecule B7-H3 expression is negatively associated with lymph node metastasis in CRC. However, B7-H3 detection might be a feasible and effective means to predict the prognosis in CRC patients.
RESUMO
In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45- nonimmune cells and 196,473 CD45+ immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors. F3+ fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However, MCAM+ fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Transcriptoma , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/genéticaRESUMO
The development of chemoresistance is a major hurdle for the treatment of colorectal cancer (CRC), which contributes remarkably to the poor clinical prognosis. Nanodrug delivery systems show great potential in overcoming chemoresistance, but limited by the lack of identification of chemoresistance targets from cancer patients. In the present study, we enrolled chemotherapy-resistant or sensitive CRC patients and used the next-generation RNA sequencing to reveal that Asporin (ASPN) is highly expressed in tumor tissues from oxaliplatin (OXA)-resistant patients and closely correlated with a poor prognosis of CRC. Downregulation of ASPN reversed OXA resistance and promoted cell apoptosis both in vitro and in vivo. To overcome ASPN-mediated OXA resistance, we constructed a nanoparticle-based co-delivery system (denoted as PPO-siASPN) for simultaneous delivery of OXA and siRNA targeting ASPN (siASPN). PPO-siASPN not only facilitated the intracellular delivery of OXA through the enhanced cellular uptake, but effectively suppressed ASPN expression for synergistic antitumor activity in vitro and in vivo. In the more clinically relevant patient-derived xenograft (PDX) mouse model, systemic administration of PPO-siASPN achieved a remarkable therapeutic effect. This study uncovered the critical role of ASPN in causing OXA resistance in CRC patients and suggests a promising nanoformulation that may be more effective than current standard-of-care medications.
Assuntos
Neoplasias Colorretais , Nanopartículas , Humanos , Camundongos , Animais , Oxaliplatina/uso terapêutico , RNA Interferente Pequeno/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Medicina de Precisão , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Nanopartículas/uso terapêutico , Linhagem Celular TumoralRESUMO
USP15 is a member of ubiquitin-specific proteases (USPs, the largest subfamily of deubiquitinases) and functions as a stabilize factor of target proteins in reversible ubiquitiantion progression. Dysregulated expression of USP15 has been observed in various cancers. However the expression profile and regulatory mechanism of USP15 in hepatocellular carcinoma (HCC) remains largely elusive. To exam the USP15 expression changes in the progression of HCC, we performed IHC analysis to test USP15 expression in a series of cancer-prone diseases including 2 normal liver tissues, 6 liver cirrhosis, 16 primary liver lesions and 15 metastases of hepatocellular carcinoma. The expression of USP15 was upregulated in various liver diseases in compared with normal tissue significantly (p < 0.05). Although no significant different of USP15 expression were discovered between cirrhotic tissue and primary tissue, its expression in HCC metastatic tissue was upregulated. Subsequently, we test the USP15 expression profile in a cohort of 66 HCC patients. USP15 expression was positively correlated with the recurrence of HCC significantly (p = 0.004). HCC patients with high USP15 expression had shorter disease free survival time in compare with those with low USP15 expression (56.9% VS 26.7%, P = 0.012). Subsequently, Cox multivariate analyses of clinical factors associated with disease free survival were performed and USP15 expression (p = 0.008) together with tumor size (p = 0.034) were proved to be independent predict factors in HCC. Then, we silenced USP15 expression in HCC cells and the results showed that downregulated USP15 expression resulting proliferation inhibition and apoptosis induction. In conclusion, our results suppose USP15 to be a potential target in HCC.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/genética , Proteases Específicas de Ubiquitina/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Ubiquitina/genéticaRESUMO
BarHlike homeobox 2 (BARX2), a homeobox gene, is associated with several types of cancers. The present study aimed to determine whether DNA methylation downregulates BARX2 expression and whether BARX2 is associated with suppression of gastric carcinogenesis. BARX2 protein expression in normal and cancerous gastric tissues and various gastric cancer (GC) cell lines was detected using immunohistochemical and western blot assays. BARX2 mRNA levels were detected using both reverse transcriptionpolymerase chain reaction (RTPCR) and quantitative PCR (qPCR). Promoter hypermethylation in GC cells was detected using methylationspecific PCR or bisulfite DNA sequencing PCR. Effects of BARX2 expression on GC cell proliferation, clonal formation, and migration were evaluated after lentivirusBARX2 transfection. The effect of stable BARX2 transfection on tumor formation was assessed in a nude xenograft mouse model. BARX2 was strongly expressed in the normal gastric mucosa, but weakly or not expressed in GC tissues and most GC cell lines. BARX2 expression was negatively correlated with DNMT (a marker for DNA methylation) expression in the gastric tissues. The BARX2 promoter fragment was hypermethylated in the GC cell lines. Overexpression of BARX2 significantly inhibited GC cell proliferation, clonal formation, and migration. Stable BARX2 transfection inhibited tumor formation in xenograft mice, which was correlated with decreased expression of Ecadherin, proliferation markers, and matrix metalloproteinases. In conclusion, BARX2 expression is aberrantly reduced in GC, which is associated with increased DNA methylation of its promoter. BARX2 inhibits GC cell proliferation, migration, and tumor formation, suggesting that BARX2 acts as a tumor suppressor in gastric carcinogenesis.
Assuntos
Metilação de DNA , Regulação para Baixo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ilhas de CpG , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Transplante de Neoplasias , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
Multidrug resistance (MDR) is one of the primary causes of chemotherapy failure in colorectal cancer (CRC), and extensive biological studies into MDR are required. The noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been demonstrated to be associated with low survival rates in patients with CRC. However, whether PVT1 serves a critical function in the MDR of CRC remains to be determined. To determine the association between PVT1 expression and 5fluorouracil (5FU) resistance in CRC, the expression levels of PVT1 mRNA in 5FUresistant CRC tissues and cell lines (HCT8/5FU and HCT116/5FU) were assessed by a reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Cytotoxicity was evaluated using a Cell Counting Kit8 assay and apoptosis rates were assessed via flow cytometry. In the present study, PVT1 mRNA was highly expressed in 5FUresistant CRC tissues and cell lines. HCT8/5FU and HCT116/5FU cells transfected with small interfering RNA PVT1 and treated with 5FU exhibited higher apoptotic rates and lower survival rates. By contrast, overexpression of PVT1 in HCT8 and HCT116 cells transfected with lentiviral vectorPVT1green fluorescent protein and treated with 5FU exhibited lower apoptosis rates and higher survival rates. RTqPCR and western blotting demonstrated that the overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistanceassociated protein 1, Pglycoprotein, serine/threonineprotein kinase mTOR and apoptosis regulator Bcl2. The present study indicates that PVT1 overexpression may promote MDR in CRC cells, and suggested that inhibition of PVT1 expression may be an effective therapeutic strategy for reversing MDR in CRC.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/farmacologia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. METHODS: The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. RESULTS: Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues (P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. CONCLUSIONS: Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.
RESUMO
OBJECTIVE: Gastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice. DATA SOURCES: The PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords "Helicobacter pylori," "Pepsinogens," and "Stomach Neoplasms." STUDY SELECTION: Original articles and reviews on the topics were selected. RESULTS: Anti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval. CONCLUSIONS: The early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.
Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Programas de Rastreamento/métodos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/microbiologia , Gastroscopia , HumanosRESUMO
OBJECTIVE: To investigate the effects of telocinobufagin on viability and apoptosis of colorectal cancer (CRC) cells and explore the mechanism of telocinobufagin-induced apoptosis. METHODS: MTT assay was performed to detect the viability of CRC cells exposed to telocinobufagin. Nuclear staining with Hoechst 33342 and flow cytometry were used to analyze the cell death of CRC cells. Expressions of proteins related with cell apoptosis and oxidative stress were determined with Western blotting. RESULTS: Telocinobufagin decreased the viability of CRC cells in a time- and dose-dependent manner. The presence of karyopycnosis and apoptotic bodies together with the results of flow cytometry suggested that telocinobufagin induced cell apoptosis to cause cell death. Western blotting showed that telocinobufagin exposure of the cells resulted in upregulated p53 and Bax protein expressions and promoted cleavage of caspase 9 and PARP. Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKBα and TAK1 and expression of survivin in the cells. CONCLUSION: Telocinobufagin can decrease the viability of CRC cells by inducing cell apoptosis, which involves p53-mediated Bax activation and inhibition of the IAP pathway.
Assuntos
Apoptose , Bufanolídeos/farmacologia , Neoplasias Colorretais/patologia , Estresse Oxidativo , Caspase 9/metabolismo , Sobrevivência Celular , Humanos , MAP Quinase Quinase Quinases/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
OBJECTIVE: To evaluate the changes in the nutritional status and immune function in patients with colorectal cancer after operation. METHODS: The indexes of the nutritional status and immune function were measured in 40 patients with colorectal cancer before and after operation and compared with the control group. RESULTS: The levels of IgM, IgG, prealbumin and transferrin were lowered after operation in these colorectal cancer patients (P<0.05), but no significant difference was noted after operation in the control group. CONCLUSION: The nutritional status and immune function in colorectal cancer patients obviously deteriorate after operation.
Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Colorretais/cirurgia , Imunoglobulina G/sangue , Estado Nutricional , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Pré-Albumina/metabolismo , Transferrina/metabolismoRESUMO
OBJECTIVE: To investigate the prognostic significance of surgical approach selection in patients with rectal cancer. METHODS: A retrospective analysis of the relation of surgical approach selection to the prognosis was conducted in 112 cases of rectal cancer between July 2000 to June 2002. RESULTS: In this group of cases, local resection of the tumor was performed in 10 cases, Dixon operation in 75 cases and Miles operation in 27 cases. A total of 106 patients survived the operations with 10 had tumor recurrence (a recurrence rate of 8.93 %). All the 10 patients receiving local resection of the tumor survived without episodes of tumor recurrence or metastasis. After the operations, 101 patients (90.18 %) retained normal sexual function and 109 (97.32 %) were with normal urinary function. CONCLUSION: The postoperative quality of life of the patients with rectal cancer very much relies on the selection of adequate surgical procedures.
Assuntos
Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgia , Adulto , Idoso , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Qualidade de Vida , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the optimal surgical approach for carcinoma in the gastric cardia. METHODS: A total of 157 patients with carcinoma in the gastric cardia were assigned into 2 groups according to the surgical approaches adopted, namely transabdominal (57 patients) and transthoracic approaches (100 patients), and the therapeutic effects of the two approaches were compared. RESULTS: In the transabdominal group, the average volume of intraoperative blood transfusion was 164.91+/-36.83 ml, average operative time 219.04+/-10.72 min and average hospital stay 14.39+/-1.39 d, with an average number of 6.04+/-2.84 lymph nodes removed. In the transthoracic group, the 4 parameters were 575.50+/-40.12 ml, 286.40+/-7.94 min, 20.32+/-0.81 d, and 3.62+/-2.56 respectively. None of the cases developed pleural effusion in the former group, which had a tumor recurrence rate of 22.80% within the follow-up period for 3 to 60 months. In contrast, 15 cases had pleural effusion in the latter group with a tumor recurrence rate of 41.00%. There was a significant difference between the two groups in terms of the therapeutic effects. CONCLUSION: Transabdominal approach is the better alternative to transthoracic one for operation of carcinoma in the gastric cardia.
Assuntos
Cárdia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
The aim of this study was to screen for polypeptides binding specifically to LoVo human colorectal cancer cells using a phage-displayed peptide library as a targeting vector for colorectal cancer therapy. Human normal colorectal mucous epithelial cells were applied as absorber cells for subtraction biopanning with a c7c phage display peptide library. Positive phage clones were identified by enzyme-linked immunosorbent assay and immunofluorescence detection; amino acid sequences were deduced by DNA sequencing. After 3 rounds of screening, 5 of 20 phage clones screened positive, showing specific binding to LoVo cells and a conserved RPM motif. Specific peptides against colorectal cancer cells could be obtained from a phage display peptide library and may be used as potential vectors for targeting therapy for colorectal cancer.
Assuntos
Neoplasias Colorretais/metabolismo , Fragmentos de Peptídeos/metabolismo , Biblioteca de Peptídeos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Humanos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/isolamento & purificação , Análise de Sequência de DNA , Células Tumorais CultivadasRESUMO
BACKGROUND AND OBJECTIVE: Protein expression in colon and rectal cancer (CRC) and paired normal tissues was examined by two-dimensional gel electrophoresis (2-DE) to identify differentially expressed proteins. MATERIALS AND METHODS: Five fresh colorectal cancer and paired adjacent normal tissues were obtained and differentially expressed protein spots were determined using PDQuest software, with identification on the basis of MALDI- TOF mass spectra. RESULTS: Compared with normal colorectal mucosa, protein abnormal expression of 65 spots varying more than 1.5 times were found in 2-DE gels from colorectal cancer samples (P<0.05); forty-two proteins were up-regulated and 23 were down-regulated; twelve protein spots were identified using mass spectrometry, of which 8 were up-regulated, including HSPB1 and Annexin A4, while 4 were down-regulated, the results being consistent with Western blot findings. CONCLUSIONS: Two-dimensional electrophoresis reference maps for CRC tissues and adjacent normal mucosa (NMC) were established and 12 differentially expressed proteins were identified. Up-regulated HSPB1 and Annexin A4 may play many important roles in the pathogenesis of colorectal cancer.
Assuntos
Colo/metabolismo , Neoplasias Colorretais/metabolismo , Mucosa Intestinal/metabolismo , Proteínas/metabolismo , Reto/metabolismo , Anexina A4/metabolismo , Regulação para Baixo , Eletroforese em Gel Bidimensional , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Humanos , Chaperonas Moleculares , Proteômica , Regulação para CimaRESUMO
Apigenin is a flavonoid belonging to the flavone structural class. It has been implicated as a chemopreventive agent against prostate and breast cancers. However, to the best of our knowledge, no published data are available regarding apigenin in colorectal cancer (CRC). The effects and mechanisms of apigenin on CRC may vary significantly. This study aimed to analyze the effects of apigenin on the growth of CRC xenografts in nude mice derived from SW480, as well as to investigate the underlying mechanisms. Whole-body fluorescence imaging is an inexpensive optical system used to visualize gene expression in small mammals using reporter genes, such as eGFP as a reporter. In our study, the expression of eGFP may reflect the size of the tumor. A terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay showed that apigenin promoted the apoptosis of CRC cells. Furthermore, the expression of five genes related to the proliferation and apoptosis of CRC, i.e., cyclin D1, BAG-1, Bcl-2, yrdC and Fas-associated protein with death domain (FADD), was detected by real-time quantitative RT-PCR. Among these genes, the up-regulated expression of FADD was noted in CRC xenograft tumors treated with apigenin. Immunohistochemistry and Western blotting confirmed the results at the protein level. Furthermore, Western blot analysis showed that apigenin induced the phosphorylation of FADD. Our findings suggest that apigenin enhances the expression of FADD and induces its phosphorylation, which may cause apoptosis of CRC cells and inhibition of tumor growth.