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Background:Malnutrition is common in patients with cancer, whichadversely affectsthesurvival and quality of life ofcancer patients.However, there is no national data on the prevalence of malnutrition inChinese cancer patients. Thisstudy aims to evaluate the prevalenceof malnutrition and quality of life(QOL)ofChinese patients with localregional, recurrentor metastatic cancer,to address the prognostic value of nutritional status and QOLon the survival of cancer patients in China and to validate the patient-generated subjective global assessment (PG-SGA) questionnaire in Chinese cancer patients.Methods:Thisisanobservational,multi-centered,and hospital-based prospective cohort study.We aimed to recruit 50,000 cancer patients (age 18and above)overan 8-year period.Data collection will occur within 48hrafter patientsare admitted to hospital, 30-days after hospital admission, and the follow-up will be conducted1-8years after enrolment. The primary outcomeisoverall survival, and secondaryoutcomes arelength of hospital stay and hospital costs. Factors measured are demographic characteristics, tumor characteristics, anthropometry measurements,hematological measurement, body composition, PG-SGAscores,Karnofsky performance status scores,and QLQ C30 scores. This protocol wasapproved by local ethical committees of all the participant hospitals.Conclusions: This multi-centered, large-scale, long-time follow-up prospective study will help diagnose malnutrition in cancer patients in China, and identify the related risk factors associated with the negative outcomes. The anticipated results will highlight the need for a truly scientific appraisal of nutrition therapy, and help to improve outcomes among cancer patients in China.Trial Registration: The trial has been registered with the Chinese Clinical Trial Registry, ChiCTR1800020329. Registered on 19 December 2018
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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.
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Objective@#To explore the clinical characteristics, treatment strategy and prognosis of adenoid cystic carcinoma of the head and neck (ACCHN).@*Methods@#A retrospective analysis of the clinical and follow-up treatment of 79 patients with ACCHN from June 2008 to July 2017 was conducted in the Cancer Hospital of Zhengzhou University.@*Results@#A total of 79 ACCHN cases, including 31 males and 48 females. The age ranged from 19 to 77 (median, 52). The clinical manifestations of ACC were related to the locations of primary tumor.The mean size of the tumor was 2.6 cm (range from 1.5 to 7.7 cm). 50 of 79 patients with a definitive pathological diagnosis received surgical resection. 59 cases received chemotherapy and 62 cases received radiotherapy. With a median follow-up of 55 months, the 5-year, 10-year survival rate of these patients were 69.6% and 54.4%, respectively.@*Conclusions@#ACCHN is an uncommon neoplasm with the characteristics of epithelial nerve growth, being inclined to distant metastasis, and high early misdiagnosis rate. The clinical manifestation, imaging and pathological result are need to be combined together to diagnose ACCHN.
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Objective@#To analyze the clinical efficacy of thalidomide combined with TP regimen (taxol+cisplatin) in treatment of advanced gastric cancer.@*Methods@#A total of 60 patients with advanced gastric cancer in the Affiliated Cancer Hospital of Zhengzhou University from February 2016 to March 2018 were enrolled. The patients were divided into two groups by using random number table method: the observation group (32 cases) taking thalidomide, oral administration 100 mg based on TP regimen before going to bed; the control group (28 cases) taking TP regimen chemotherapy only. Both groups received 75 mg/m2 doses of cisplatin, intravenous infusion, 25 mg/m2 per day, for 3 d. Paclitaxel dose was 150 mg/m2, intravenous infusion for 1 day, 3-week was one course, and the efficacy was evaluated after at least 2 course of treatment.@*Results@#The incidence of gastrointestinal adverse reactions including nausea and vomiting was 21.8% (7/32) in the observation group, and was 64.3% (18/28) in the control group, and the difference was statistically significant (χ 2 = 11.051, P = 0.001), but there were no statistically significant differences in the incidence of morning faint, constipation, bone marrow suppression, liver and kidney injury and other adverse reactions between the two groups (all P > 0.05). The effective rates in the observation group and the control group were 43.8% (14/32) and 39.3% (11/28), respectively, and the disease control rates in the observation group and the control group were 84.4% (27/32) and 78.6% (22/28), respectively. There were no significant differences in the effective rates and the disease control rates between the two groups (χ 2 = 0.122, P = 0.726; χ2 = 0.336, P = 0.562). The improvement and significant improvement rate of sleeping quality, pain, Eastern Cooperative Oncology Group (ECOG) score was 71.9% (23/32), 53.1% (17/32), 56.2% (18/32), respectively in the observation group, and 17.9% (5/28), 14.3% (4/28), 21.4% (6/28), respectively in the control group, and the difference between the two groups was statistically significant (all P < 0.05).@*Conclusions@#Thalidomide combined with TP regimen in treatment of advanced gastric cancer patients can improve the efficacy of chemotherapy and the quality of life. It also has a good tolerance to side effects.
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Objective@#To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism.@*Methods@#From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay.@*Results@#The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues (P<0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues (P<0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p (r=-0.613, P=0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P<0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3′-UTR reporter assay confirmed that miRNA-96-5p binds to the 3′UTR of FoxQ1.@*Conclusion@#miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.
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Objective To analyze the clinical efficacy of thalidomide combined with TP regimen (taxol+cisplatin) in treatment of advanced gastric cancer. Methods A total of 60 patients with advanced gastric cancer in the Affiliated Cancer Hospital of Zhengzhou University from February 2016 to March 2018 were enrolled. The patients were divided into two groups by using random number table method:the observation group (32 cases) taking thalidomide, oral administration 100 mg based on TP regimen before going to bed; the control group (28 cases) taking TP regimen chemotherapy only. Both groups received 75 mg/m 2 doses of cisplatin, intravenous infusion, 25 mg/m2 per day, for 3 d. Paclitaxel dose was 150 mg/m2, intravenous infusion for 1 day, 3-week was one course, and the efficacy was evaluated after at least 2 course of treatment. Results The incidence of gastrointestinal adverse reactions including nausea and vomiting was 21.8％ (7/32) in the observation group, and was 64.3％ (18/28) in the control group, and the difference was statistically significant (χ2= 11.051, P= 0.001), but there were no statistically significant differences in the incidence of morning faint, constipation, bone marrow suppression, liver and kidney injury and other adverse reactions between the two groups (all P> 0.05). The effective rates in the observation group and the control group were 43.8％(14/32) and 39.3％ (11/28), respectively, and the disease control rates in the observation group and the control group were 84.4％ (27/32) and 78.6％ (22/28), respectively. There were no significant differences in the effective rates and the disease control rates between the two groups (χ2= 0.122, P= 0.726; χ2= 0.336, P= 0.562). The improvement and significant improvement rate of sleeping quality, pain, Eastern Cooperative Oncology Group (ECOG) score was 71.9％ (23/32), 53.1％ (17/32), 56.2％ (18/32), respectively in the observation group, and 17.9％ (5/28), 14.3％ (4/28), 21.4％ (6/28), respectively in the control group, and the difference between the two groups was statistically significant (all P< 0.05). Conclusions Thalidomide combined with TP regimen in treatment of advanced gastric cancer patients can improve the efficacy of chemotherapy and the quality of life. It also has a good tolerance to side effects.
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Objective To assess the value of serum carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels in the diagnosis of gastric cancer in elderly patients.Methods This prospective study included 104 elderly patients with gastric cancer at our hospital from March 2015 to December 2016 to serve as an experimental group.Moreover,104 elderly patients with benign gastric lesions were enrolled to serve as a control group.Serum CEA and CA19-9 levels were compared between the two groups.The diagnostic specificity,sensitivity,and validity for gastric cancer were calculated by using CEA or CA19-9 alone or the two in combination.Results Serum CEA and CA19-9 levels in the experimental group were significantly higher than in the control group(t =3.001 and 5.110,P =0.039 and 0.016,respectively);The specificity,sensitivity,and validity of CEA and CA19-9 in combination were significantly higher than when each of the measures was used alone(x2 =2.101 and 2.109,P =0.031 and 0.019,respectively).Serum CEA levels showed good predictive power for both lymph node metastasis of gastric cancer(Z =5.109,P =0.002) and liver metastasis of gastric cancer(Z =3.910,P =0.026);Serum CA19-9 levels could predict lymph node metastasis of gastric cancer (Z =4.189,P =0.003) Conclusions Serum CEA and CA19-9 in combination have high sensitivity and validity for gastric cancer detection;Elevated CEA can predict gastric cancer metastasis and elevated CA19-9 may predict lymph node metastasis.
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Objective@#To explore the clinical characteristics, surgical procedures and prognosis of solid pseudopapillary tumor of the pancreas(SPTP).@*Methods@#The clinical and follow-up data of 55 cases with SPTP in Henan Tumor Hospital from June 2005 to April 2015 were retrospectively analyzed.@*Results@#There were 55 SPTP cases, including 7 males and 48 females. The age ranged from 16 to 76 (median, 33). Clinical presentations of SPTP were not specific. The mean size of the tumor was 7.6 cm (range from 2 to 25cm). Pancreatic head and tail were the most common locations of SPTP. All the patients received surgical resection with a definitive pathological diagnosis. Some immunohistochemical markers were mostly positive, including β-catenin, Vim, Syn, CD10, CD56, PR, etc. With a median follow-up of 53 months, the 1-year, 2-year and 5-year survival rate were 98.1%, 96.1% and 94.0%, respectively.@*Conclusions@#SPTP is an uncommon exocrine pancreatic neoplasm with low malignant potential, which frequently occurs in young women. Preoperative imaging can provide evidence for the selection of treatment modalities among which surgical resection ispreferred. Diagnosis still relies on pathology and immunohistochemistry.
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<p><b>OBJECTIVE</b>To predict and identify the target gene of miR-145, and to explore the underlying mechanism of the inhibition of miR-145 on drug resistance to Oxaliplatin (L-OHP) in human colorectal cancer cells.</p><p><b>METHODS</b>L-OHP-resistant human colorectal cancer cell line (HCT116/L-OHP) was established in vitro by exposing to increased concentrations of L-OHP in cell culture medium. MiR-145-mimics and its negative control (NC-miRNA) were transfected into HCT116/L-OHP cells using liposome to establish HCT116/L-OHPover-expressing miR-145 and HCT116/L-OHP. The target genes of miR-145 were predicted by bioinformatic analysis, and validated by dual luciferase activity assay. After determination of G protein coupled receptor 98(GPR98) as target gene, corresponding plasmids were constructed and transfected to establish HCT116/L-OHPover-expressing GPR98 and HCT116/L-OHP. HCT116/L-OHP cells over-expressing both GPR98 and miR-145 (HCT116/L-OHP) were acquired through modification of the binding sites of GPR98 cDNA with miR-145. CCK-8 assay was used to assess the proliferation (A value) and sensitivity to L-OHP (the lower the IC50, the stronger the sensitivity) in HCT116/L-OHP cells. Real-time quantitative PCR was used to measure the mRNA expression of miR-145 and GPR98. Western blot was used to examine the protein expression of GPR98 and drug-resistant associated protein, such as P-glycoprotein (gp), multiple drug-resistance protein 1(MRP1), cancer-inhibition gene PTEN.</p><p><b>RESULTS</b>HCT116/L-OHP cell line was successfully established with ICof (42.34±1.05) mg/L and miR-145 mRNA expression of 0.27±0.04, which was higher than (9.81±0.95) mg/L (t=39.784, P=0.000) and lower than 1.00±0.09 (t=13.021, P=0.000) in HCT116 cells. Based on HCT116/L-OHP cells, HCT116/L-OHPcells were established successfully, with relative miR-145 expression of 10.01±1.05, which was higher than 1.06±0.14 in HCT116/L-OHPand 1.00±0.16 in HCT116/L-OHP (F=161.797, P=0.000). GPR98 was identified to be the target gene of miR-145. The relative mRNA and protein expressions of GPR98 in HCT116/L-OHPcells were 8.48±0.46 and 1.71±0.09, respectively, which were higher than those in HCT116/L-OHP(mRNA: 3.65±0.40, protein: 1.21±0.10) and HCT116/L-OHP (mRNA: 3.49±0.35, protein: 1.22±0.08; all P<0.05). The A value was 1.31±0.10, and the relative protein expressions of P-gp and MRP1 were 1.53±0.18 and 1.49±0.20 in HCT116/L-OHPcells, which were higher than those in HCT116/L-OHP (A value: 0.82±0.08, relative protein expression: 1.00±0.06 and 1.21±0.13, all P<0.05). The A value was 0.89±0.08, and the relative protein expressions of P-gp and MRP were 1.02±0.24 and 1.38±0.25 in HCT116/L-OHPcells, which were higher than those in HCT116/L-OHP(A value: 0.20±0.05, relative protein expression: 0.20±0.07, 0.55±0.10, all P<0.05). The relative protein expression of PTEN in HCT116/L-OHPcells was 0.12±0.03, which was lower than 1.25±0.14 in HCT116/L-OHP cells(P<0.05). In addition, relative protein expressions of P-gp and MRP1 were 1.02±0.24 and 1.38±0.25 in HCT116/L-OHPcells, which were higher than those in HCT116/L-OHPcells (0.20±0.07 and 0.55±0.10), while PTEN expression in HCT116/L-OHPcells was lower as compared to HCT116/L-OHPcells (1.41±0.16 vs. 1.98±0.13, P<0.05).</p><p><b>CONCLUSION</b>MiR-145 inhibits drug resistance to L-OHP of HCT116 cells through suppressing the expression of target gene GPR98.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Cell Line, Tumor , Physiology , Colorectal Neoplasms , Down-Regulation , Genetics , Drug Resistance, Neoplasm , Genetics , Physiology , HCT116 Cells , Physiology , In Vitro Techniques , MicroRNAs , Genetics , Pharmacology , Multidrug Resistance-Associated Proteins , Organoplatinum Compounds , Pharmacology , PTEN Phosphohydrolase , RNA, Messenger , Receptors, G-Protein-Coupled , GeneticsABSTRACT
Objective To investigate the effects of mechanism of silent information regulator of transcription 1 (SIRT1) in the drug-resistance of colonic cancer.Methods The clinical data of 25 colonic cancer patients with 5-Fu-resistance and 30 colonic cancer patients with chemosensitivity who were admitted to the Henan Tumor Hospital from December 2012 to December 2013 were retrospectively analyzed.The specimens of colonic cancer were collected for study.(1) The protein expression of SIRT1 in patients with drug-resistance or chemotherapeutic sensitivity was tested by immunohistochemical staining.The protein expression of SIRT1 in the HCT116 and HCT1 16/5-FU cells was detected by Western blot.(2)HCT116/5-FU cells were interfered by siRNA and divided into the blank control group (cells untreated),the empty vector group (cells treated by siRNA) and the SIRT1 silence group (cells treated by SIRT1 siRNA).The protein expression of the HCT116/5-FU cells were inhibited by the c-Jun N-terminal kinase (JNK) and then divided into the SP600125 group [cells were treated by JNK signaling pathway inhibitor SP60012 (concentration:30 μmol/L)for 12 hours],the DMSO group [cells were treated by DMSO (cells were treated by 0.1％ DMSO for 12 hours] and the control group (cells were treated by cell culture media).(3) Serine in the SIRT1 ser47 was mutated to alanine or aspartic acid,and mutations S47A (S47A group,serine to alanine) and S47D (S47D group,serine to aspartic acid) ; Untransfected HCT116/5-FU cells were in the S47 wild type group,and apCMV-3Tag-3 cells transfected by empty vector were served as negative control; all the HCT116/5-FU cells were interfered by 5-FU (concentration:8 μmol/L) for 12 hours.HTC116 cells and HTC116/5-FU cells were treated by SIRT1 inhibitor resveratrol at concentrations of 0,1,10,50,100 nmol/L and SIRT1 activator niacinamide at concentrations of 0,1,2,3,4,5 ng/L.Cell proliferation was detected by MTF.(4) Cell apoptosis was detected by flow cytometry.(5) The expressions of related genes were detected by real-time PCR.(6)The expressions of related proteins were detected by western blot.The count data were analyzed using the chi-square test.The measurement data with normal distribution were presented as (x) ± s.The comparison among groups were analyzed using the one-way analysis of variance and LSD-t test.The pairwise comparisons were analyzed using the t text.Results (1) The results of immunohistochemical staining were as follows.The positive expressions of SIRT1 in patients with chemotherapeutic sensitivity and drug-resistance were 16.7％ (5/30) and 92.0％ (23/25),respectively,with significant difference (x2 =30.965,P ＜ 0.05).The relative mRNA and protein expressions of SIRT1 in HCT116/5-FU cells with drug-resistance were 1.870 ± 0.100 and 1.660 ± 0.109,which were significantly higher than 1.000 ± 0.070 and 1.000 ± 0.050 in HCT116/5-FU cells without drug-resistance (t =11.721,8.963,P ＜ 0.05).(2) The results of MTT were as follows.The proliferation rates of HCT116/5-FU cells treated by resveratrol at concentrations of 0,1,10,50 nmol/L were 100％ ±12％,105％± 14％,129％ ± 10％ and 144％ ± 17％,which were significantly higher than 41％ ± 10％,49％ ±11％,74％ ± 16％ and 105％ ± 17％ of HCT116 cells which were treated by reseratrol at the same contrations (t =8.226,-7.236,6.673,3.510,P ＜0.05).The proliferation rates of HCT116/5-FU cell treated by niacinamide at concentrations of 0,1,2 ng/L were 87％ ± 12％,78％ ± 12％,69％ ± 11％,which were significantly higher than 36％ ± 6％,32％± 5％,30％± 6％ of HCT116 cells which were treated by niacinamide at the same concentrations (t =-8.593,-8.006,-7.000,P ＜ 0.05).The proliferation rates of HCT116/5-FU cells in the blank control group,the empty vector group and the SIRT1 silence group were 100％± 8％,99％ ±9％,37％ ± 6％,with significant differences among the 3 groups (F =66.597,P ＜ 0.05),and the proliferation rate of HCT116/5-FU cells in the SIRT1 silence group was significantly lower than that in the blank control group (t =10.113,P ＜0.05).(3) The results of flow cytometry were as follows.The apoptotic rates of HCT116/5-FU cells in the SIRT1 silence group,the empty vector group and the blank control group were 60％ ± 5％,36％ ± 4％,35％ ±4％,with significant differences among the 3 groups (F =36.549,P ＜ 0.05),and the apoptotic rates of HCT1 16/5-FU cells in the SIRT1 silence group were significantly higher than that in the blank control group and the empty vector group (t =-7.215,-7.084,P ＜0.05).(4)The results of RT-PCR were as follows.The relative expression rates of P-gp mRNA in the HCT116/5-FU cells in the SIRT1 silence group,the empty vector group and the blank control group were 0.320 ± 0.030,0.990 ± 0.060,1.000 ± 0.090,with significant differences among the 3 groups (F =10.107,P ＜ 0.05),and the relative expression rate of P-gp mRNA in the SIRT1 silence group was significantly lower than that in the blank control group (t =11.463,P ＜ 0.05).The relative expression rates of P-gp mRNA in the HCT116/5-FU cells in the SP600125 group,the DMSO group and the control group were 0.240 ±.0.040,0.990 ± 0.100,1.000 ± 0.070,with significant difference among the 3 groups (F =19.002,P＜0.05),and the relative expression rates of P-gp mRNA in the SP600125 group was significantly lower than that in the control group (t =7.301,P ＜0.05).(5) The results of western blot were as follows.The relative expression rates of p-JNK protein in the HCT116/5-FU cells in the blank control group,the empty vector group and the SIRT1 silence group were 1.000 ± 0.090,1.090 ± 0.020,0.080 ± 0.010,with significant difference among the 3 groups (F =12.130,P ＜ 0.05).The ratios of p-SIRT1-S27/T-SIRT1,p-SIRT1-T530/T-SIRT1,p-SIRT1-S47/T-SIRT1 were 1.158 ±0.140,1.209 ±0.150,3.760 ±0.150 in HCT116 cells treated by 5-FU,and 1.120 ±0.109,1.130 ±0.100,2.160 ±0.110 in HCT116 cells treated by DMSO,with significant differences (F =9.763,10.261,P ＜0.05).The ratios of p-SIRT1-S47/T-SIRT1 in HCT116 cells treated by 5-FU and DMSO were 3.760 ± 0.150 and 2.160 ± 0.110,which were significantly higher than 0.940 ± 0.040 and 1.121 ± 0.110 in HCT116/5-FU cells (t =14.721,21.335,P ＜ 0.05).(6) The proliferation rates of HCT116/ 5-FU cells in the S47 wild type group,the negative control group,the S47A group and the S47D group were 41％± 31％,39％ ± 4％,64％ ± 2％ and 26％ ± 5％,with significant differences among the 4 groups (F =6.371,P ＜ 0.05).Conclusions SIRT1 promotes the proliferation of drug-resistant colonic cancer cells and increases the expression of P-gp via JNK signaling pathway,there by enhances cellular drug resistance.SIRT1 S47 is the critical site for 5-FU-resistance in HCT116/5-FU cells.
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Background and purpose:Rectal small cell carcinoma is high malignant tumor and prone to early metastasis. It is rare in the clinical and its prognosis is poor. The aim of this article was to analyze clinical characteristics and summarize the diagnosis,treatment and prognosis of rectal small cell carcinoma.Methods:Clinical data of 16 cases with rectal small cell carcinoma conifrmed by pathology from Jan. 2001 to Jan. 2013 in the Tumor Hospital Affiliated to Zhengzhou University Hospital were analyzed retrospectively.Results:Among the 16 rectal small cell carcinoma patients (mean age is 58.5 years), 9 were male, 7 were female; 4 cases in stageⅡ, 7 cases in stageⅢ and 5 cases in stageⅣ. Ten cases underwent surgical treatment, of which 6 cases underwent radical surgery, 4 cases underwent palliative surgery;6 cases received chemotherapy alone, 2 cases received chemoradiotherapy, 2 cases did not receive any treatment postoperatively. Five cases were lost opportunity for operation, of which 3 cases underwent chemotherapy alone and 2 cases underwent chemoradiotherapy. One case did not receive any treatment. Among 10 cases of resection of the lesions, 5 cases had vascular invasion and 7 cases had local lymph node metastasis. All patients received 7-65 months of follow-up. The median survival was 15.4 months. The 6 months, 1 year, 2 years, 3 years and 5 years survival rates were 58.4%, 46.2%, 26.6%, 13.1% and 6.2% respectively. The prognosis of patients was associated with tumor staging, presence of vascular invasion and lymph node metastasis, and type of operation (P0.05).Conclusion:The biologic behavior of rectal small cell carcinoma which is a rare disease and similar to small cell lung cancer, and its prognosis is poor. Treatment methods include surgery, radiotherapy and chemotherapy. The overall result is poor.
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<p><b>OBJECTIVE</b>To investigate the prognostic impact of different chemotherapy strategies on small cell esophageal carcinoma (SCEC).</p><p><b>METHODS</b>The clinical data of 62 patients with histologically confirmed SCEC treated in our department between January 2006 and April 2011 were retrospectively analyzed. There were 39 patients with limited stage (LS) and 23 patients with extensive stage (ES) SCEC according to the Veterans Administration Lung Study Group staging system. Cox's hazard regression model was used to determine the prognostic factors, and Chi-square test was used to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank analyses were used to estimate and compare the survival rates.</p><p><b>RESULTS</b>The chemotherapy combined with local therapy group was significantly better than chemotherapy alone group in median survival time (MST) (20.8 vs. 7.6 months, P<0.05). The MST was 18.0 months and the 1-, 2-, and 3-year overall survival rates (OS) were 68.8%, 38.6%, and 20.9%, respectively, for all the 62 patients. Etoposide plus cisplatin or carboplatin (EP/CP) did not result in significantly longer MST, compared with that of the cases treated by other combination chemotherapy (P>0.05, for either LS or ES cases). Multivariate analysis showed that the VALSG stage, the number of chemotherapy cycles (≥ 4), and treatment modality are independent prognostic factors (P<0.05).</p><p><b>CONCLUSIONS</b>SCEC is a tumor characterized by high malignancy and poor prognosis. Chemotherapy combined with local therapy is an effective treatment for SCEC, and appropriate chemotherapy cycles (≥ 4) may improve the survival time. EP/CP, as commonly used multidrug chemotherapy regimen, is not superior to other combination chemotherapy.</p>
Subject(s)
Humans , Antineoplastic Agents , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carboplatin , Carcinoma, Small Cell , Drug Therapy , Mortality , Pathology , Chi-Square Distribution , Cisplatin , Esophageal Neoplasms , Drug Therapy , Mortality , Pathology , Etoposide , Multivariate Analysis , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Objective To investigate the relationship between RAD51 135G ＞ C polymorphism and prognosis in triple-negative breast cancer patients by retrospective analysis.Methods The clinical data of 62 triplenegative breast cancer patients were collected.The 62 cases underwent standard chemotherapy and radiotherapy after tumor resection from Jan.2004 to Dec.2010 in Affiliated Cancer Hospital of Zhengzhou University.RAD51 135G ＞ C polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) technology.The survival curve about progress free and overall survival time were then made.Results The median progress free and overall survival time in triple-negative breast cancer patients with or with-out RAD51 135G ＞ C polymorphism were(77.00 ±5.55)and(89.00 ± 10.40) months vs(99.00 ±4.26)and (103.00 ±4.30) months.The difference had statistical significance(P =0.039 and 0.015 respectively).Conclusion RAD51 135G ＞ C polymorphism is related with prognosis of triple-negative breast cancer patients,which might be a prognostic factor for breast cancer.
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BACKGROUND:Abdominal incision healing is not only related with the patient’s own situation, but also closely related with the surgeon's suture technique, suture method, choice of stitches. ＜br> OBJECTIVE:To compare the absorbable sutures and silk sutures for abdominal incision. ＜br> METHODS:Total y 153 colorectal cancer patients, including 91 males and 62 females, aged 30-82 years, were randomly divided into observation group (n=78) and control group (n=75). An abdominal midline incision was made in al patients receiving radical surgery of colorectal cancer. The Vicryl suture and silk suture were respectively used in the observation and control groups for abdominal incision closure. Suturing time, length of hospital stay, incision infection, disruption of wound, fat liquefaction of wound and rejection were compared between two groups. ＜br> RESULTS AND CONCLUSION:The suturing time and length of hospital stay were less in the observation group than the control group (P＜0.05). In the observation group, there were three cases of incision infection, but no incision dehiscence and rejection occurred;in the control group, there were 10 cases of incision infection, 4 cases of incision dehiscence, and 5 cases of rejection. A significant difference was found in the incision infection, dehiscence and rejection between the two groups (P＜0.05). Hospitalization expenses and fat liquefaction of incision had no difference between the two groups. these findings indicate that the Vicryl plus as an absorbable suture is simple, effective and safe that can promote wound healing and reduce complications.
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Primary esophageal small cell carcinoma (PESCC) is a rare disease first described by McKeown in 1952. PESCC is characterized by high malignancy, distant metastasis, and poor prognosis. The incidence of PESCC has significantly increased world-wide in recent years. However, practice guidelines that concern the histological origin, clinical diagnosis methods, therapies, and prog-nosis of PESCC are still not well established because of the paucity of cases and lack of large prospective randomized research. This ar-ticle aims to outline recent advances in the clinical and therapeutic aspects of PESCC as well as review the different opinions concerned to better understand PESCC and solve clinical problems.
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<p><b>OBJECTIVE</b>To investigate the role of death associated protein kinase(DAPK) in colon cancer drug-resistance.</p><p><b>METHODS</b>Immunohistochemistry was used to detect DAPK expression in colon carcinoma tissues of 61 cases and adjacent tissues of 32 cases. 5-fluorouracil (5-FU)-induced drug-resistant colon cancer cell lines HCT116/5-FU model was established. DAPK-siRNA was transfected into cells to down-regulate the DAPK gene expression (DAPK-siRNA grouyp), FAM-siRNA was transfected as control group, and DAPK over-expression plasmid vectors were constructed to up-regulate the DAPK gene expression(DAPK over-expression group). Real-time quantitative PCR and Western blotting were used to examine the mRNA and protein expression levels of DAPK, multidrug resistance protein (MRP) and P- glycoprotein (P-gp). MTT and flow cytometry were used to detect cell proliferation and apoptosis for cells treated with 5-FU (8 mg/L) and cells without treatment of 5-FU in 3 groups respectively.</p><p><b>RESULTS</b>Positive expression rate of DAPK in colon cancer tissues was significantly lower than that in adjacent normal tissues [18.0% (11/61) vs. 90.6% (29/32), P < 0.05]. Compared with FAM-siRNA group, DAPK mRNA and protein expression levels were significantly lower in DAPK-siRNA group, but significantly higher in DAPK over-expression group (P<0.05). After treatment of 5-FU, cell proliferation was significantly inhibited, but cell apoptosis was significantly increased in DAPK over-expression group compared to FAM-siRNA group (P < 0.05). Cell proliferation and apoptosis were not significantly different between DAPK siRNA and FAM-siRNA groups (all P < 0.05). Compared with FAM-siRNA group, DAPK over-expression could significantly reduce the mRNA and protein levels of MRP and P-gp, whereas DAPK siRNA had no obvious such effects.</p><p><b>CONCLUSION</b>DAPK can inhibit the proliferation and promote the apoptosis in drug-resistant colon cancer cells, and it probably enhances the sensitivity of cancer cells to drugs by down-regulating the mRNA and protein levels of MRP and P-gp.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Antineoplastic Agents , Apoptosis , Cell Proliferation , Colorectal Neoplasms , Drug Therapy , Death-Associated Protein Kinases , Metabolism , Drug Resistance, Neoplasm , Fluorouracil , Genetic Vectors , HCT116 Cells , RNA, Messenger , RNA, Small Interfering , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To investigate the roll of bone sialoprotein (BSP), a secreted glycoprotein, found in mineralized tissues in the development and progression of human esophageal squamous cell carcimoma (ESCC), and explore its association with clinicopathological characteristics and five-year survival of the patients.</p><p><b>METHODS</b>The expression of BSP was determined in 211 primary ESCC tumors and their paired nontumorous tissues using tissue-array, RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>Primary ESCC tissues showed a significantly higher expression rate of BSP mRNA than their paired nontumorous tissues (93.8% vs. 16.6%, P < 0.001), the same with BSP protein (56.9% vs. 31.3%, P < 0.001). The expression rate of BSP protein was correlated to lymph node metastasis and TNM stage (P < 0.05). The 5-year survival rate of BSP protein-positive ESCC patients was significantly lower than that of BSP protein-negative ESCC patients (P < 0.05). Multivariate analysis showed that tumor differentiation, TNM staging and BSP protein expression were independent factors affecting the prognosis of ESCC patients (P < 0.05).</p><p><b>CONCLUSIONS</b>The abnormal expression of BSP may play a significant role in the malignant progression and prognosis of ESCC, and BSP might be a marker reflecting the biologial behavior of ESCC.</p>
Subject(s)
Humans , Blotting, Western , Carcinoma, Squamous Cell , Diagnosis , Metabolism , Esophageal Neoplasms , Diagnosis , Metabolism , Immunohistochemistry , Integrin-Binding Sialoprotein , Genetics , Metabolism , Lymphatic Metastasis , Neoplasm Staging , Prognosis , RNA, Messenger , Survival RateABSTRACT
Objective To investigate the expression of β-catenin and Oct-4 in colonal carcinoma and explore the relationship with recurrence and metastasis after operation. MethodsImmunohistochemical analysis was used to evaluate the expression of β-catenin and Oct-4.The correlation of β-catenin and Oct-4 expression with tumor cell differentiation,T stage,N stage and metastasis was analyzed.The gene expression of Oct-4 was examined by RT-PCR in 20 frozen tumor tissues and normal tissues adjacent to tumor.Results Thirty-five patients had metastasis. The positive rates of β-catenin and Oct-4 expression were significantly higher in metastasis group than in the non-metastasis group (65.71％ vs 31.11％,51.43 ％vs 13.33 ％,x2 =9.843,P =0.002,x2 =13.605,P =0.001).Expression of β-catenin and Oct-4 was not associated with differentiation,T stage or N stage.The positive expression rate of Oct-4 in colonal carcinoma tissues was significantly higher than that in normal tissues.Metastatic rates in patients with positive expression of β-catenin and Oct-4 was higher than that in negative expression.The survival analysis showed that time of metastasis was significantly different in two groups of patients (P ＜0.05).Conclusion The expression of β-catenin and Oct-4 in tumor tissues is related to metastasis of colonal cancer after surgery and might be used to predict metastasis of colonal cancer after operation.
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Objective To compare the short-term efficacy and adverse effects of docetaxe or oxaliplatin combined with capecitabine in the treatment of late-staged gastric cancer in aged patients. Methods Eighty-two aged patients with late-staged gastric cancer were randomly divided into two groups,of which 38 patients were treated group) ,and 44 patients were treated with oxaliplatin (100 mg/m2 ivgtt on 1st day) and eapecitabine (2000 mg/1 cycle). Results There is no failure of follow-up. In the docetaxe group,the effective rate was 52.63% (20/38) and 54.55 % (24/44) for the docetaxe and oxaliplatin group,respectively (P>0.05). The median progression-free survival(PFS) in the docetaxe group (6.1 months) was similar to that in the oxaliplatin group (6.3 months) (P>0.05). Gastrointestinal response,myelosuppression and neurotoxicity (Ⅰ or Ⅱ level) were the most common ad-verse effects observed in both groups (P>0.05). No chemotherapy-related death was observed. Conclusions The short-term efficacy of decetaxe or oxaliplatin combined with capecitabine in the treatment of late-staged gastric cancer in aged patients is similar,and the adverse effects are all within tolerance limits.
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Background and purpose: In recent years indirubin-3'-monoxime has been found to be capable of inhibiting some cell proliferation in vitro and in vivo studies, but human colon cancer HT-29 cells, therefore the purpose in this paper was to study the effect of indirubin-3'-monoxime on proliferation and apoptosis of HT-29 cells and its associated mechanism. Methods: HT-29 cells were treated with indirubin-3'-monoxime. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay, flow cytometry (FCM) was used to measure the apoptosis rate. RT-PCR was used to measure the transcription of apoptosis suppressor gene bcl-2, survivin and apoptosis promoting gene Bar. Results: Indimbin-3'-monoxime inhibited growth of HT-29 cells in a dose-dependent and time-dependent manner (F=11.25, P<0.01). The apoptosis rate increased after the treatment by indirubin-3'-monoxime at 10 μmol/L. There were significant differences between different time groups (F=195.25, P<0.01). The transcription of survivin (F=78.75, P<0.01) and Bax (F=87.61, P<0.01) mRNA in HT-29 cells were increased; the transcription of bcl-2 was significantly decreased (F=95.82, P<0.01). Conclusion: Indirubin-3'-monoxime has obviously inhibited proliferation and induce apoptosis of colon cancer HT-29 cells, its mechanism may be related to decrease the bcl-2/Bax ratio.