1.Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis.
Xiao-Ming DU ; Liu-Hua WANG ; Xiao-Wen CHEN ; Yi-Xiao LI ; Yu-Cong LI ; Yu-Wen CAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(3):305-312
The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.
Antineoplastic Agents
;
therapeutic use
;
Biomarkers, Tumor
;
genetics
;
metabolism
;
Colorectal Neoplasms
;
diagnosis
;
drug therapy
;
mortality
;
pathology
;
Esophageal Neoplasms
;
diagnosis
;
drug therapy
;
mortality
;
pathology
;
Gastrointestinal Tract
;
metabolism
;
pathology
;
Gene Expression
;
Humans
;
Neoadjuvant Therapy
;
methods
;
Neoplasm Grading
;
Neoplasms, Vascular Tissue
;
diagnosis
;
drug therapy
;
mortality
;
secondary
;
Prognosis
;
SOXB1 Transcription Factors
;
genetics
;
metabolism
;
Stomach Neoplasms
;
diagnosis
;
drug therapy
;
mortality
;
pathology
;
Survival Analysis
2.Association between expressions of HSP70, HSP90 and efficacy of chemotherapy in colorectal cancer patients with unresectable liver metastasis.
Chao-wu CHEN ; Zhong-cheng HUANG ; Yun LIU ; Zhi-jun YUAN ; Guo-qing NING ; Li-xin TAN
Chinese Journal of Gastrointestinal Surgery 2009;12(4):346-349
OBJECTIVETo investigate the association between expressions of HSP70, HSP90 and efficacy of chemotherapy in colorectal cancer patients with unresectable liver metastasis.
METHODSData of 52 colorectal cancer cases, whose primary colorectal focuses were resected but hepatic metastatic tumors were unresectable, were reviewed retrospectively. All the patients underwent FOLFOX4 regimen well. Immunohistochemistry assay was applied to determine the expressions of HSP70 and HSP90 in primary focus tissues. The number and size of hepatic metastatic tumors pre- and post-chemotherapy were compared by CT scanning.
RESULTSPartial remission(PR) rate was 33.3% in cases with up-regulated expression of HSP70, while 64.5% in cases with down-regulated expression of HSP70, whose difference was significant. PR rate was 50% in cases with up-regulated expression of HSP90, and 53.1% in the others with down-regulated expression of HSP90, whose difference was not significant.
CONCLUSIONSFOLFOX4 regimen has advantages in cases with lower HSP70 expression over those with higher HSP70 expression. HSP90 expression level is not associated with the efficacy of FOLFOX4 regimen.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; HSP70 Heat-Shock Proteins ; metabolism ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; secondary ; Male ; Middle Aged ; Prognosis ; Treatment Outcome
3.Increasing the alpha 2, 6 Sialylation of Glycoproteins May Contribute to Metastatic Spread and Therapeutic Resistance in Colorectal Cancer.
Gut and Liver 2013;7(6):629-641
Abnormal glycosylation due to dysregulated glycosyltransferases and glycosidases is a key phenomenon of many malignancies, including colorectal cancer (CRC). In particular, increased ST6 Gal I (beta-galactoside alpha 2, 6 sialyltransferase) and subsequently elevated levels of cell-surface alpha 2, 6-linked sialic acids have been associated with metastasis and therapeutic failure in CRC. As many CRC patients experience metastasis to the liver or lung and fail to respond to curative therapies, intensive research efforts have sought to identify the molecular changes underlying CRC metastasis. ST6 Gal I has been shown to facilitate CRC metastasis, and we believe that additional investigations into the involvement of ST6 Gal I in CRC could facilitate the development of new diagnostic and therapeutic targets. This review summarizes how ST6 Gal I has been implicated in the altered expression of sialylated glycoproteins, which have been linked to CRC metastasis, radioresistance, and chemoresistance.
Antigens, CD/*metabolism
;
Colorectal Neoplasms/*metabolism/pathology/*therapy
;
Drug Resistance, Neoplasm
;
Glycoproteins/*metabolism
;
Humans
;
Liver Neoplasms/secondary
;
Lung Neoplasms/secondary
;
Radiation Tolerance
;
Receptor, Epidermal Growth Factor/metabolism
;
Sialic Acids/*metabolism
;
Sialyltransferases/*metabolism
4.Lentivirus-mediated RNA interference suppresses APRIL expression and enhances chemosensitivity in colorectal cancer cells.
Jing GUAN ; Ai-min SUN ; Li-hui WANG ; Mei-rong HE
Journal of Southern Medical University 2011;31(9):1600-1604
OBJECTIVETo investigate the effects of lentivirus-mediated RNA interference (RNAi) targeting a proliferation-inducing ligand (APRIL) on the chemosensitivity to 5-FU of colorectal cancer cell line LoVo.
METHODSThe lentiviral vector siRNA-APRIL was constructed and verified by PCR and DNA sequencing. LoVo cells were transfected with siRNA-APRIL plasmid, non-targeting siRNA plasmid, or empty plasmid. Forty-eight hours after the transfection, the cells were examined for APRIL expression using Western blot. Seventy-two hours after treatment with 10 µg/ml 5-FU, flow cytometry was used to detect the cell apoptosis and cell cycle changes. The cell growth inhibition rate following 5-FU exposure was detected by MTT assay.
RESULTSPCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting APRIL gene was successfully inserted into the lentiviral vector. siRNA-APRIL transfection resulted in obviously reduced expression of APRIL in LoVo cells. After 5-FU exposure, the apoptosis rate of siRNA-APRIL-transfected cells were increased to (21.12∓3.35)%, significantly higher than that in cells transfected with the non-targeting plasmid or the empty plasmid [(13.06∓1.92)% and (12.28∓1.79)%, respectively, P<0.01]; the cell number in G0/G1 phase increased while that in G2/M phase decreased in siRNA-APRIL-transfected cells. The growth inhibition rate in siRNA-APRIL group was (59.67∓5.03)%, significantly higher than that in the other two groups [(42.33∓4.16)% and (39.67∓4.73)%, respectively, P<0.01].
CONCLUSIONLentivirus-mediated RNAi targeting APRIL can effectively suppress the expression of APRIL in LoVo cells and enhance the chemosensitivity of the cells to 5-FU.
Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; drug therapy ; metabolism ; pathology ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; Lentivirus ; genetics ; RNA Interference ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; genetics ; metabolism
5.Consensus and dispute in histopathology of gastrointestinal tract.
Mao-de LAI ; Xiao-dong TENG ; Fang-ying XU
Chinese Journal of Pathology 2011;40(5):289-291
Antibodies, Monoclonal
;
therapeutic use
;
Antibodies, Monoclonal, Humanized
;
Antineoplastic Agents
;
therapeutic use
;
Cadherins
;
genetics
;
metabolism
;
Carcinoma, Papillary
;
pathology
;
Cetuximab
;
Colorectal Neoplasms
;
drug therapy
;
genetics
;
pathology
;
Consensus
;
Dissent and Disputes
;
Drug Delivery Systems
;
Epithelial-Mesenchymal Transition
;
Gastrointestinal Neoplasms
;
classification
;
pathology
;
Genes, ras
;
Humans
;
Mutation
;
Neoplasm Invasiveness
;
Neoplastic Syndromes, Hereditary
;
genetics
;
metabolism
;
pathology
;
Neuroendocrine Tumors
;
classification
;
pathology
;
Precancerous Conditions
;
pathology
;
Stomach Neoplasms
;
genetics
;
metabolism
;
pathology
6.Expressions of orotate phosphoribosyltransferase in colorectal carcinoma and its correlations with toxicities of chemotherapy.
Qiumei DONG ; Saihua HUANG ; Ying LI ; Jianhua LIU
Journal of Southern Medical University 2012;32(8):1179-1181
OBJECTIVETo investigate the expression of orotate phosphoribosyltransferase (OPRT) in colorectal carcinoma and analyze its correlations with the toxicities of chemotherapy.
METHODSThe expression of OPRT mRNA was detected using RT-PCR in colorectal carcinoma tissues and paired adjacent normal tissues from 58 patients receiving FOLFOX6 regimen chemotherapy. The toxicities of the chemotherapy were recorded, and the correlations between OPRT mRNA expression and the toxicities were analyzed.
RESULTSOPRT mRNA expression was significantly higher in the tumor tissues than in the corresponding normal tissues (P=0.001), but OPRT expression in the tumor tissues was not correlated with the toxicities of the chemotherapy (P>0.05). OPRT level in the normal tissues showed a significant positive correlation with the occurrence of diarrhea in these cases (P=0.013).
CONCLUSIONOPRT expression in colorectal carcinoma tissues is not correlated with the toxicities of 5-FU-based regimen, but OPRT expression in the normal tissues can help predict the toxicities associated with 5-FU.
Adult ; Aged ; Antimetabolites, Antineoplastic ; therapeutic use ; toxicity ; Colorectal Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; Fluorouracil ; therapeutic use ; toxicity ; Humans ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Middle Aged ; Orotate Phosphoribosyltransferase ; metabolism
7.Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.
Zhi-wei ZHOU ; De-sen WAN ; Guo-qiang WANG ; Jing-qing REN ; Zhen-hai LU ; Shao-xian TANG ; Yan-li YE ; Gong CHEN ; Su-xia LIN
Chinese Journal of Gastrointestinal Surgery 2006;9(2):161-164
OBJECTIVETo study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.
METHODSIn vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group. The number of liver metastases, the size of primary tumor and the toxicity were examined after 2 weeks postoperatively. The expression of vascular endothelial growth factor (VEGF) in liver metastases was detected by immunohistochemistry, and tumor microvessel density (MVD) was measured by immunostaining with CD34 and factor VIII (monoclonal antibodies.
RESULTSIn vitro, YH-16 inhibited the growth of colon cancer cells and vascular endothelial cells, with the IC50 at (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg/ml respectively. In vivo high-dose YH-16 and 5-FU had a remarkable inhibitory effect on liver metastasis, and the combination group showed significant enhancement on this effect (P< 0.05). The combination group and 5-FU group could inhibit the growth of primary tumor, but not found in YH-16 group. The toxicity of YH-16 was lower than that of 5-FU (P< 0.05), and the difference was not found in the toxicity between combination group and 5-FU group (P > 0.05). Expression of VEGF in liver metastases was clearly inhibited by YH-16 in combination with 5-FU or 5-FU alone compared to the control group, and MVD in middle-dose and high-dose YH-16 group, 5-FU group and combination group was lower than that in control group (P< 0.05).
CONCLUSIONSThe angiogenesis inhibitor YH-16 can inhibit liver metastasis of colorectal cancer through inhibiting the growth of vascular endothelial cells. YH-16 in combination with 5-FU has additive effect on inhibitory activity against liver metastasis.
Angiogenesis Inhibitors ; therapeutic use ; Animals ; Cell Line, Tumor ; Colorectal Neoplasms ; drug therapy ; pathology ; Drug Therapy, Combination ; Female ; Fluorouracil ; therapeutic use ; Liver Neoplasms ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Vascular Endothelial Growth Factor A ; metabolism
8.G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers.
Wenbin LI ; Xinghua ZHANG ; Yongkang CHEN ; Yibin XIE ; Jiancheng LIU ; Qiang FENG ; Yi WANG ; Wei YUAN ; Jie MA
Protein & Cell 2016;7(2):130-140
Granulocyte colony-stimulating factor (G-CSF) is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells (MDSCs) promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer (CAC) model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for colitis-associated cancer.
Animals
;
Carcinogenesis
;
Colitis
;
complications
;
Colorectal Neoplasms
;
complications
;
drug therapy
;
immunology
;
metabolism
;
Female
;
Gene Expression Regulation, Neoplastic
;
Granulocyte Colony-Stimulating Factor
;
genetics
;
metabolism
;
Immunotherapy
;
Mice
;
Molecular Targeted Therapy
;
Myeloid Cells
;
immunology
;
metabolism
;
pathology
9.Ursolic acid synergistically enhances the therapeutic effects of oxaliplatin in colorectal cancer.
Jianzhen SHAN ; Yanyan XUAN ; Qi ZHANG ; Chunpeng ZHU ; Zhen LIU ; Suzhan ZHANG
Protein & Cell 2016;7(8):571-585
Oxaliplatin is a key drug in chemotherapy of colorectal cancer (CRC). However, its efficacy is unsatisfied due to drug resistance of cancer cells. In this study, we tested whether a natural agent, ursolic acid, was able to enhance the efficacy of oxaliplatin for CRC. Four CRC cell lines including SW480, SW620, LoVo, and RKO were used as in vitro models, and a SW620 xenograft mouse model was used in further in vivo study. We found that ursolic acid inhibited proliferation and induced apoptosis of all four cells and enhanced the cytotoxicity of oxaliplatin. This effect was associated with down-regulation of Bcl-xL, Bcl-2, survivin, activation of caspase-3, 8, 9, and inhibition of KRAS expression and BRAF, MEK1/2, ERK1/2, p-38, JNK, AKT, IKKα, IκBα, and p65 phosphorylation of the MAPK, PI3K/AKT, and NF-κB signaling pathways. The two agents also showed synergistic effects against tumor growth in vivo. In addition, ursolic acid restored liver function and body weight of the mice treated with oxaliplatin. Thus, we concluded that ursolic acid could enhance the therapeutic effects of oxaliplatin against CRC both in vitro and in vivo, which offers an effective strategy to minimize the burden of oxaliplatin-induced adverse events and provides the groundwork for a new clinical strategy to treat CRC.
Animals
;
Antineoplastic Combined Chemotherapy Protocols
;
pharmacology
;
Cell Line, Tumor
;
Colorectal Neoplasms
;
drug therapy
;
metabolism
;
pathology
;
Drug Synergism
;
Female
;
Humans
;
Mice
;
Mice, Nude
;
Neoplasm Proteins
;
metabolism
;
Organoplatinum Compounds
;
agonists
;
pharmacology
;
Oxaliplatin
;
Triterpenes
;
agonists
;
pharmacology
;
Xenograft Model Antitumor Assays
10.Patrinia scabiosaefolia Inhibits Growth of 5-FU-Resistant Colorectal Carcinoma Cells via Induction of Apoptosis and Suppression of AKT Pathway.
Si-Zhou HUANG ; Wang-Yu LIU ; Yue HUANG ; A-Ling SHEN ; Li-Ya LIU ; Jun PENG
Chinese journal of integrative medicine 2019;25(2):116-121
OBJECTIVE:
To investigate the effects of ethanol extract of Patrinia scabiosaefolia (EEPS) on chemo-resistance of colorectal cancer cells (CRC) and explore the possible molecular mechanisms.
METHODS:
5-fluorouracil (5-FU)-resistant human colorectal carcinoma cell line (HCT-8/5-FU) and its parental cells HCT-8 were treated with EEPS (0, 0.25, 0.50, 1 or 2 mg/mL), or 5-FU (0, 100, 200, 400, 800 or 1600 μmol/L). The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the cell viability. Cell density was observed by phase-contrast microscope, cell counting and colony formation assay were used to determine the cell proliferation of HCT-8/5-FU cells treated with 0, 0.5, 1 or 2 mg/mL EEPS. Cell apoptosis was determined by Hoechst staining. Western-blot was performed to detect the phosphorylation of AKT as well as the protein expression level of B-cell CLL/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).
RESULTS:
Compared with HCT-8 cells, MTT assay results indicated that HCT-8/5-FU cells were resistant to 5-FU treatment (P<0.05), and sensitive to EEPS treatment (P>0.05). Moreover, compared with untreated HCT-8/5-FU cells, 1 and 2 mg/mL of EEPS treatment significantly reduced cell density, cell number, inhibited cell survival (P<0.05), and induced apoptosis in HCT-8/5-FU cells. Furthermore, 1 and 2 mg/mL of EEPS significantly decreased the phosphorylation level of p-AKT and Bcl-2 protein expression, and increased the expression of Bax protein (P<0.05).
CONCLUSION
EEPS is a promising therapeutic agent that may overcome chemo-resistance in cancer cells, likely through suppression of the AKT pathway and promotion of cancer cell apoptosis.
Apoptosis
;
drug effects
;
Cell Line, Tumor
;
Cell Proliferation
;
drug effects
;
Cell Survival
;
drug effects
;
Colorectal Neoplasms
;
drug therapy
;
pathology
;
Drug Resistance, Neoplasm
;
drug effects
;
Fluorouracil
;
pharmacology
;
therapeutic use
;
Humans
;
Patrinia
;
chemistry
;
Phosphorylation
;
drug effects
;
Proto-Oncogene Proteins c-akt
;
metabolism
;
Signal Transduction
;
drug effects
;
Tumor Stem Cell Assay
;
bcl-2-Associated X Protein
;
metabolism