Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on ...Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on squamous cell carcinoma. Methods: Influence of AK auto Abs on the proliferation of Tca cells was observed by MTT colorimetry. Telomerase activity of cultured Tca cells and human keratinocytes was determined by telomeric repeat amplication protocol-ELISA (TRAP-ELISA) and polyacrylamide gel elec-trophoresis (PAGE). After being treated with AK auto Abs for 36 h at a concentration of 4, 8, 16 mg/L respectively, the changes of telomerase activity of Tea cells were also detected by TRAP-ELISA and PAGE. Results: MTT colorimetric determination showed that the capacity of proliferation of Tca cells correlated negatively with the concentration of AK auto Abs (r= -0. 74, P<0. 01). TRAP-ELISA and PAGE showed that telomerase activity of Tca cells increased significantly compared to that of cultured human keratinocytes (t = 3. 5396, P<0. 01). AK auto Abs at a concentrations of 4, 8, 16 mg/L had significant dose-dependent inhibitory effects on telomerase activity of Tca cells (r= - 0. 8358, P<0. 01). Conclusion: AK auto Abs have a significant dose-dependent inhibitory effect on the proliferation of cultured Tea cells. AK auto Abs inhibit telomerase activity of cultured Tca cells with dose-dependent pattern. It suggests that decrease of telomerase activity may play an important role in the inhibitory effects of AK auto Abs on squamous cell carcinoma.展开更多
Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data...Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.展开更多
The expression of c-erbB-1 and c-erbB-2 oncogenes were investigated by immunohistochemistry using monoclonal antibodies to c-erbB-2 and c-erbB-2 protein in 43 cases of basal cell carcinoma (BCC) and 26 cases of squamo...The expression of c-erbB-1 and c-erbB-2 oncogenes were investigated by immunohistochemistry using monoclonal antibodies to c-erbB-2 and c-erbB-2 protein in 43 cases of basal cell carcinoma (BCC) and 26 cases of squamous cell carcinoma (SCC). We found that the expression of c-erbB-1 oncogene in all BCC increased by different degrees and the expression of c-erbB-2 oncogene in BCC was significantly reduced or lost when compared to that in normal epidermal cells. Furthermore, apparent negative and positive rela-tionships were observed respectively between the tumor differentiation and the expression of cerbB-1 and c-erbB-2 oncogenes in SCC. It is suggested that the abnormal expression of c-erbB-1 and c-erbB-2 oncogenes in BCC and SCC may play a role in the development of skin tumors. The pattern of the c-erbB-1 and c-erbB-2 oncogenes expression in SCC may assist in distinguishing the biological behavior and prognosis of SCC.展开更多
Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the c...Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.展开更多
Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma(HNSCC)and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival...Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma(HNSCC)and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival of HNSCC.This study investigated the function of iASPP playing in proliferation and invasion of HNSCC in vitro.Methods HNSCC cell line Tu686 transfected with Lentiviral vector-mediated iASPP-specific shRNA and control shRNA were named the shRNA-iASPP group and shRNA-NC group,respectively.The non-infected Tu686 cells were named the CON group.CCK-8 assay,flow cytometry,transwell invasion assay were performed to detect the effects of iASPP inhibition in vitro.Results Our results demonstrated that the proliferation of shRNA-iASPP cells at the time of 72 h(F=32.459,P=0.000),96 h(F=51.407,P=0.000),120 h(F=35.125,P=0.000)post-transfection,was significantly lower than that of shRNANC cells and CON cells.The apoptosis ratio of shRNA-iASPP cells was 9.42%±0.39%(F=299.490,P=0.000),which was significantly higher than that of CON cells(2.80%±0.42%)and shRNA-NC cells(3.18%±0.28%).The percentage of shRNA-iASPP cells in G0/G1 phase was 74.65%±1.09%(F=388.901,P=0.000),which was strikingly increased,compared with that of CON cells(55.19%±1.02%)and shRNA-NC cells(54.62%±0.88%).The number of invading cells was 56±4 in the shRNA-iASPP group(F=84.965,P=0.000),which decreased significantly,compared with the CON group(111±3)and the shRNA-NC group(105±8).The survival rate of shRNA-iASPP cells administrated with paclitaxel was highly decreased,compared with CON cells and shRNA-NC cells(F=634.841,P=0.000).Conclusion These results suggest iASPP may play an important role in progression and aggressive behavior of HNSCC and may be an efficient chemotherapeutic target for the treatment of HNSCC.展开更多
NEOPLASMS derive from small intestine are rareand most cases are adenocarcinomas andcarcinoid.1 Squamous cell carcinoma of smallintestine is even rarer and only few casesreported in literature.1 In this article, we re...NEOPLASMS derive from small intestine are rareand most cases are adenocarcinomas andcarcinoid.1 Squamous cell carcinoma of smallintestine is even rarer and only few casesreported in literature.1 In this article, we report a case of a68-year-old male who underwent a laparotomy due toperforation of the small intestine and was diagnosed withsquamous cell carcinoma of the small intestine.展开更多
Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of...Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.展开更多
Background:p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors.In this study,we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck...Background:p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors.In this study,we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma(HNSCC)cell death.Methods:CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively.The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay,flow cytometric analysis and MTT.The effects of DIRAS3 and p53 re-expression on Akt phosphorylation,oncogene expression,and the interaction of 4 E-BP1 with eIF4 E were determined by real-time PCR,Western blotting and immunoprecipitation analysis.The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy,LC3 fluorescence microscopy and Western blotting.The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model.Results:TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis(P<0.001).MTT and flow cytometric analysis revealed that DIRAS3 and p53 reexpression significantly inhibited proliferation and induced cell cycle arrest(P<0.001).Mechanistically,the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3(STAT3)and upregulated p21WAF1/CIP1 and Bax(P<0.001).DIRAS3 and p53 re-expression also inhibited Akt phosphorylation,increased the interaction of eIF4 E with 4 E-BP1,and reduced the expression of c-Myc,cyclin D1,vascular endothelial growth factor(VEGF),fibroblast growth factor(FGF),epidermal growth factor receptor(EGFR)and Bcl-2(P<0.001).Moreover,the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus(50.00%±4.55%vs.4.67%±1.25%,P<0.001).LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux,resulting in overall impaired autophagy.Finally,the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model[(3.12±0.75)mm^(3) vs.(189.02±17.54)mm^(3),P<0.001].Conclusions:The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.展开更多
Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morp...Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen （PCNA） and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results： Amlodipine concentration of 8.25umol/L （1/2 of ICs0） affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion： The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.展开更多
To investigate the inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2. Methods： HepG-2 cells were cultured in the presence of the different concentrations of mycophenolate m...To investigate the inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2. Methods： HepG-2 cells were cultured in the presence of the different concentrations of mycophenolate mofetil in vitro. MTT assay was used to analyze the inhibition of cell viability conferred by mycophenolate mofetil. Cell apoptosis was observed using Hoechst33258 staining, and the percentage of HepG-2 cells at different cell cycles was determined through flow cytometry. The ability of cell adhesion was evaluated by in vitro adhesion assay. Gene expressions of factors （ICAM-1 and VCAM-1） were detected by RT-PCR. Results： Mycophenolate mofetil significantly inhibited the growth of HepG-2 cells by inducing the apoptosis of cells and this drug also inhibited the adhesion of HepG-2 cells in a dose-dependent manner. Marked morphological changes characterized in cell apoptosis were demonstrated through Hoechst33258 staining. In addition, mycophenolate mofetil decreased the proportion of S phase cells and increased that of G0/G1 phase cells. [^3H]-Thymidine uptake assay indicated that the application of mycophenolate mofetil at different concentrations significantly inhibited the cell proliferation. RT-PCR identified the expression levels of ICAM-1 and VCAM-1 genes in liver cancer cells after cultured for 72 h with different concentrations of drug. An inverse relationship was found between the expressions of ICAM-1 and VCAM-1 and drug concentrations. Conclusion： Mycophenolate mofetil has remarkable inhibitory effect on hepatocarcinoma HepG-2 cells.展开更多
Objective： To observe the effect of the artesunate （ART） on cellular proliferation in vitro, to search for the possible anti-tumor mechanism of ART on endometrial carcinoma at the molecular level and to provide the...Objective： To observe the effect of the artesunate （ART） on cellular proliferation in vitro, to search for the possible anti-tumor mechanism of ART on endometrial carcinoma at the molecular level and to provide the experimental and theoretical foundations for the clinical applications of ART. Methods： The cell proliferation was observed by microscope; MTT was used to examine the effects of ART on proliferation of HEC-1B cells, and flow cytometric analysis was used to detect cell cycle and apoptosis. The human endometrial carcinoma HEC-1B cells were conventionally cultured; ART was administered with a concentration of 40 μg/ml before the total RNA were extracted, mRNA expression of Survivin, Caspase-3, N-Cadherin, E-Cadherin, Fibronectinl and Cox-2 were detected using RT-PCR. Results： ART reduced proliferation in human endometrial carcinoma cell line HEC-1B in a dose- and time-dependent effect. The cells of G0/G1 stage were significantly increased （P〈0.05）, but the cells of G2/M stages were significantly decreased （P〈0.05）, so it has shown that the cell cycle was probably blocked in G0/G1 stage. After intervention with ART at 20 and 80 μg/ml for 48 h, cellular apoptosis rate respectively was （36.42±0.77）% and （11.77±0.58）%, and the difference was statistically significant compared with the control （[6.64±0.191%, P〈0.01）. The expression of Cox-2 mRNA in the ART group was lower than those of control group, yet the expression of Caspase-3 and E-Cadherin mRNA in the ART group was higher than those of control group. Conclusion： ART can inhibit HEC-1B cell growth and proliferation in a dose- and time-dependent manner. Furthermore, ART can induce apoptosis in a dose-dependent manner. ART is able to downregulate Cox-2 mRNA expression and to upregulate E-Cadherin and Caspase-3 mRNA expression. So we can conclude that ART could induce the endometrial carcinoma HEC-1B cell apoptosis and inhibit tumor cell proliferation.展开更多
Locally recurrent head and neck squamous cell carcinoma(HNSCC)is often unresectable,and a repeat course of radiotherapy is associated with incremental toxicities.Boron neutron capture therapy(BNCT)is a novel targeted ...Locally recurrent head and neck squamous cell carcinoma(HNSCC)is often unresectable,and a repeat course of radiotherapy is associated with incremental toxicities.Boron neutron capture therapy(BNCT)is a novel targeted radiotherapy modality that can achieve a high dose gradient between cancerous and adjacent normal tissues.However,the relationships among the dose resulting from BNCT,tumor response to BNCT,and survival are not completely understood.Recently,a study published in Radiotherapy and Oncology investigated the efficacy of BNCT in the treatment of patients with locally recurrent HNSCC and the factors associated with favorable treatment response and survival.In this article,the findings,strengths and limitations of this study are discussed in depth,and the significance of the study and motivations for future research are highlighted.展开更多
Synchronous bilateral multiple chromophobe cell renal carcinoma is rare; here we report a case diagnosed with bilateral renal multiple tumors complicated with a cyst in the right kidney. Retroperitoneal laparoscopic b...Synchronous bilateral multiple chromophobe cell renal carcinoma is rare; here we report a case diagnosed with bilateral renal multiple tumors complicated with a cyst in the right kidney. Retroperitoneal laparoscopic bilateral nephron sparing surgery was performed and there was no serious postoperative renal dysfunction. Pathological and immunohistochemical diagnoses of both tumors were chromophobe cell renal carcinoma. The patient has been doing well without any evidence of recurrence or metastasis for 6 months.展开更多
Objective To evaluate the application of weak cation exchange (WCX) magnetic bead-based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in detecting differentially expressed...Objective To evaluate the application of weak cation exchange (WCX) magnetic bead-based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in detecting differentially expressed proteins in the urine of renal clear cell carcinoma (RCCC) and its value in the early diagnosis of RCCC.Methods Eleven newly diagnosed patients (10 males and 1 female, aged 46-78, mean 63 years) of renal clear cell carcinoma by biopsy and 10 healthy volunteers (all males, aged 25-32, mean 29.7 years) were enrolled in this study. Urine samples of the RCCC patients and healthy controls were collected in the morning.Weak cation exchange (WCX) bead-based MALDI-TOF MS technique was applied in detecting differential protein peaks in the urine of RCCC. ClinProTools2.2 software was utilized to determine the characteristic proteins in the urine of RCCC patients for the predictive model of RCCC.Results The technique identified 160 protein peaks in the urine that were different between RCCC patients and health controls; and among them, there was one peak (molecular weight of 2221.71 Da) with statistical significance (P=0.0304). With genetic algorithms and the support vector machine, we screened out 13 characteristic protein peaks for the predictive model.Conclusions The application of WCX magnetic bead-based MALDI-TOF MS in detecting differentiallyexpressed proteins in urine may have potential value for the early diagnosis of RCCC.展开更多
This article reports a case of simultaneous occurrence of 2 primary renal tumors of different histology, a transitional cell carcinoma and a renal cell carcinoma. in the same kidney. The histological, immunohistochemi...This article reports a case of simultaneous occurrence of 2 primary renal tumors of different histology, a transitional cell carcinoma and a renal cell carcinoma. in the same kidney. The histological, immunohistochemical and ultrastructural changes of the tumors were described. A review of the literature to date revealed this case to be rare. only 24 other cases were reported previously.展开更多
Objective:To analyze the p16INK4a genomic alteration and expression status in 3 human pancreatic carcinoma cell lines with different potential of metastasis. Methods:Using PCR-SSCP, Dot-blot and immunohistochemistry, ...Objective:To analyze the p16INK4a genomic alteration and expression status in 3 human pancreatic carcinoma cell lines with different potential of metastasis. Methods:Using PCR-SSCP, Dot-blot and immunohistochemistry, the p16INK4a genomic mutation and expression were analyzed on DNA, mRNA and protein levels in 3 human pancreatic carcinoma cell lines Patu8902, Patu8988 and SW1990, which had different potential of metastasis. Results: (1) On DNA level: there was no deletion of p16INK4a Exon Ⅰ in 3cell lines; p16INK4a Exon Ⅱ was only deleted in Patu8902 while no deletion in Patu8988 and SW1990. No insertion, microdeletion and point mutation were found in the 3 cell lines. (2) On RNA level: the expression of p16INK4a protein was negative in Patu8902, low expressed in SW1990, but highly expressed in Patu8988.(3) On protein level: P16 protein was strongly stained in Patu8988, much lower in SW1990, but not stained in Patu8902. Conclusion:The genomic type and expression of p16INK4a are quite different in 3 pancreatic carcinoma cell lines which have different potential of metastasis. It is suggested that genomic homozygous deletion and low expression of mRNA might relate to the potential of metastasis of pancreatic cell lines. In other words, dysfunction of p16INK4a might be an important mechanism in the metastasis of pancreatic carcinoma.展开更多
The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of t...The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.展开更多
This study was aimed at providing an experimental model for the research of HCC. Twelve specimens that were pathologically identified as HCC were cultured in vitro . To investigate their biological characteristics, th...This study was aimed at providing an experimental model for the research of HCC. Twelve specimens that were pathologically identified as HCC were cultured in vitro . To investigate their biological characteristics, the survived cells were morphologically展开更多
Objective: To study the effect of 5-Aza-2’ -deoxycytidine (5-Aza-cdR) on tumour suppressor gene p16 expres- sion in hepatocellular carcinoma cells. Method: Expression of pl6 mRNA and protein in hepatocellular carcino...Objective: To study the effect of 5-Aza-2’ -deoxycytidine (5-Aza-cdR) on tumour suppressor gene p16 expres- sion in hepatocellular carcinoma cells. Method: Expression of pl6 mRNA and protein in hepatocellular carcinoma cell lines SMMC-7721 and HePG2 before and after treatment with 5-Aza-cdR were analyzed via reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemistrty Results: The expression levels of p16 mRNA and protein were increased dramatically after treatment with 5-Aza-cdR. Conclusion: Our data show that, 5-Aza-2’ -deoxycytidine can increase the expression of pl6 gene both at transcription and translation. The findings suggested that 5-Aza-cdR may reactivate the pl6 gene by demethylation.展开更多
The effects of two antisense oligodeoxynucleotides on the expression of c-Ha-ras proto-oncogene and the growth of human gastric carcinoma cell lines were observed. Synthetic 15-mer directed at the region of the transl...The effects of two antisense oligodeoxynucleotides on the expression of c-Ha-ras proto-oncogene and the growth of human gastric carcinoma cell lines were observed. Synthetic 15-mer directed at the region of the translational initiation site of c-Ha-ras proto-oncogene (ASO-r) greatly inhibited the proliferation (55. 61%,P<0. 05) and DNA synthesis (76. 79%,P<0. 05) of MGc-803 cell line. It also inhibited the proliferation (62. 02%,P<0. 05) and DNA synthesis (76. 78%, P<0. 05) of SGc-7901 cell line. A reduction in intracellular P21 ras protein levels in MGc-803 cell line was observed 6 h after the treatment with ASO-r and maintained over 12 h. Another synthetic 15-mer targeted against the initiation codon and downstream 4 codons of c-myc proto-oncogene (ASOm) inhibited only DNA synthesis of MGc-803 cell line (71. 37%, P<0. 05). The control 15-mer did not inhibit the expression of P21 protein and proliferation of these cell lines. These experiments seemed to provide evidence that ASO-r could be effective in inhibiting the expression of c-Ha-ras proto-oncogene and controlling the growth of human gastric carcinoma cells,and that the over-expression of c-Ha-ras proto-oncogene might mainly be associated with the malignant proliferation of human gastric carcinoma cells.展开更多
文摘Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on squamous cell carcinoma. Methods: Influence of AK auto Abs on the proliferation of Tca cells was observed by MTT colorimetry. Telomerase activity of cultured Tca cells and human keratinocytes was determined by telomeric repeat amplication protocol-ELISA (TRAP-ELISA) and polyacrylamide gel elec-trophoresis (PAGE). After being treated with AK auto Abs for 36 h at a concentration of 4, 8, 16 mg/L respectively, the changes of telomerase activity of Tea cells were also detected by TRAP-ELISA and PAGE. Results: MTT colorimetric determination showed that the capacity of proliferation of Tca cells correlated negatively with the concentration of AK auto Abs (r= -0. 74, P<0. 01). TRAP-ELISA and PAGE showed that telomerase activity of Tca cells increased significantly compared to that of cultured human keratinocytes (t = 3. 5396, P<0. 01). AK auto Abs at a concentrations of 4, 8, 16 mg/L had significant dose-dependent inhibitory effects on telomerase activity of Tca cells (r= - 0. 8358, P<0. 01). Conclusion: AK auto Abs have a significant dose-dependent inhibitory effect on the proliferation of cultured Tea cells. AK auto Abs inhibit telomerase activity of cultured Tca cells with dose-dependent pattern. It suggests that decrease of telomerase activity may play an important role in the inhibitory effects of AK auto Abs on squamous cell carcinoma.
基金supported by the National Innovation and Enterpreneurship Training Program for College Students(202210367002)the Key Laboratory Open Project of An-hui Province(AHCM2022Z004).
文摘Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.
文摘The expression of c-erbB-1 and c-erbB-2 oncogenes were investigated by immunohistochemistry using monoclonal antibodies to c-erbB-2 and c-erbB-2 protein in 43 cases of basal cell carcinoma (BCC) and 26 cases of squamous cell carcinoma (SCC). We found that the expression of c-erbB-1 oncogene in all BCC increased by different degrees and the expression of c-erbB-2 oncogene in BCC was significantly reduced or lost when compared to that in normal epidermal cells. Furthermore, apparent negative and positive rela-tionships were observed respectively between the tumor differentiation and the expression of cerbB-1 and c-erbB-2 oncogenes in SCC. It is suggested that the abnormal expression of c-erbB-1 and c-erbB-2 oncogenes in BCC and SCC may play a role in the development of skin tumors. The pattern of the c-erbB-1 and c-erbB-2 oncogenes expression in SCC may assist in distinguishing the biological behavior and prognosis of SCC.
文摘Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.
基金Supported by Beijing Medical Health Public Welfare Foundation(grant no.YWJKJJHKYJJ-B17468 and running period:2017.09.01-2020.09.01)
文摘Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma(HNSCC)and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival of HNSCC.This study investigated the function of iASPP playing in proliferation and invasion of HNSCC in vitro.Methods HNSCC cell line Tu686 transfected with Lentiviral vector-mediated iASPP-specific shRNA and control shRNA were named the shRNA-iASPP group and shRNA-NC group,respectively.The non-infected Tu686 cells were named the CON group.CCK-8 assay,flow cytometry,transwell invasion assay were performed to detect the effects of iASPP inhibition in vitro.Results Our results demonstrated that the proliferation of shRNA-iASPP cells at the time of 72 h(F=32.459,P=0.000),96 h(F=51.407,P=0.000),120 h(F=35.125,P=0.000)post-transfection,was significantly lower than that of shRNANC cells and CON cells.The apoptosis ratio of shRNA-iASPP cells was 9.42%±0.39%(F=299.490,P=0.000),which was significantly higher than that of CON cells(2.80%±0.42%)and shRNA-NC cells(3.18%±0.28%).The percentage of shRNA-iASPP cells in G0/G1 phase was 74.65%±1.09%(F=388.901,P=0.000),which was strikingly increased,compared with that of CON cells(55.19%±1.02%)and shRNA-NC cells(54.62%±0.88%).The number of invading cells was 56±4 in the shRNA-iASPP group(F=84.965,P=0.000),which decreased significantly,compared with the CON group(111±3)and the shRNA-NC group(105±8).The survival rate of shRNA-iASPP cells administrated with paclitaxel was highly decreased,compared with CON cells and shRNA-NC cells(F=634.841,P=0.000).Conclusion These results suggest iASPP may play an important role in progression and aggressive behavior of HNSCC and may be an efficient chemotherapeutic target for the treatment of HNSCC.
基金Supported by Young Scientists Fund of National Natural Science Foundation of China(81101707)Zhejiang Traditional Chinese Medicine Foundation Project(2014ZB119)Science and Technology Bureau of Jiaxing(2012AY1071-2)
文摘NEOPLASMS derive from small intestine are rareand most cases are adenocarcinomas andcarcinoid.1 Squamous cell carcinoma of smallintestine is even rarer and only few casesreported in literature.1 In this article, we report a case of a68-year-old male who underwent a laparotomy due toperforation of the small intestine and was diagnosed withsquamous cell carcinoma of the small intestine.
基金the National Key Research&Development Program of China(2022YFF1100305)the National Natural Science Foundation of Ningxia Province(2021AAC02019)the Major Projects of Science and Technology in Anhui Province(201903a06020021,201904a06020008,202004a06020042,202004a06020052).
文摘Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.
基金supported by Funding for the Basic Research of the Ministry of Sciences and Technology,Sichuan Province(2015JY0090)the National Natural Science Foundation of China(81972546,81602373)。
文摘Background:p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors.In this study,we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma(HNSCC)cell death.Methods:CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively.The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay,flow cytometric analysis and MTT.The effects of DIRAS3 and p53 re-expression on Akt phosphorylation,oncogene expression,and the interaction of 4 E-BP1 with eIF4 E were determined by real-time PCR,Western blotting and immunoprecipitation analysis.The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy,LC3 fluorescence microscopy and Western blotting.The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model.Results:TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis(P<0.001).MTT and flow cytometric analysis revealed that DIRAS3 and p53 reexpression significantly inhibited proliferation and induced cell cycle arrest(P<0.001).Mechanistically,the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3(STAT3)and upregulated p21WAF1/CIP1 and Bax(P<0.001).DIRAS3 and p53 re-expression also inhibited Akt phosphorylation,increased the interaction of eIF4 E with 4 E-BP1,and reduced the expression of c-Myc,cyclin D1,vascular endothelial growth factor(VEGF),fibroblast growth factor(FGF),epidermal growth factor receptor(EGFR)and Bcl-2(P<0.001).Moreover,the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus(50.00%±4.55%vs.4.67%±1.25%,P<0.001).LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux,resulting in overall impaired autophagy.Finally,the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model[(3.12±0.75)mm^(3) vs.(189.02±17.54)mm^(3),P<0.001].Conclusions:The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.
文摘Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen （PCNA） and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results： Amlodipine concentration of 8.25umol/L （1/2 of ICs0） affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion： The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.
文摘To investigate the inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2. Methods： HepG-2 cells were cultured in the presence of the different concentrations of mycophenolate mofetil in vitro. MTT assay was used to analyze the inhibition of cell viability conferred by mycophenolate mofetil. Cell apoptosis was observed using Hoechst33258 staining, and the percentage of HepG-2 cells at different cell cycles was determined through flow cytometry. The ability of cell adhesion was evaluated by in vitro adhesion assay. Gene expressions of factors （ICAM-1 and VCAM-1） were detected by RT-PCR. Results： Mycophenolate mofetil significantly inhibited the growth of HepG-2 cells by inducing the apoptosis of cells and this drug also inhibited the adhesion of HepG-2 cells in a dose-dependent manner. Marked morphological changes characterized in cell apoptosis were demonstrated through Hoechst33258 staining. In addition, mycophenolate mofetil decreased the proportion of S phase cells and increased that of G0/G1 phase cells. [^3H]-Thymidine uptake assay indicated that the application of mycophenolate mofetil at different concentrations significantly inhibited the cell proliferation. RT-PCR identified the expression levels of ICAM-1 and VCAM-1 genes in liver cancer cells after cultured for 72 h with different concentrations of drug. An inverse relationship was found between the expressions of ICAM-1 and VCAM-1 and drug concentrations. Conclusion： Mycophenolate mofetil has remarkable inhibitory effect on hepatocarcinoma HepG-2 cells.
文摘Objective： To observe the effect of the artesunate （ART） on cellular proliferation in vitro, to search for the possible anti-tumor mechanism of ART on endometrial carcinoma at the molecular level and to provide the experimental and theoretical foundations for the clinical applications of ART. Methods： The cell proliferation was observed by microscope; MTT was used to examine the effects of ART on proliferation of HEC-1B cells, and flow cytometric analysis was used to detect cell cycle and apoptosis. The human endometrial carcinoma HEC-1B cells were conventionally cultured; ART was administered with a concentration of 40 μg/ml before the total RNA were extracted, mRNA expression of Survivin, Caspase-3, N-Cadherin, E-Cadherin, Fibronectinl and Cox-2 were detected using RT-PCR. Results： ART reduced proliferation in human endometrial carcinoma cell line HEC-1B in a dose- and time-dependent effect. The cells of G0/G1 stage were significantly increased （P〈0.05）, but the cells of G2/M stages were significantly decreased （P〈0.05）, so it has shown that the cell cycle was probably blocked in G0/G1 stage. After intervention with ART at 20 and 80 μg/ml for 48 h, cellular apoptosis rate respectively was （36.42±0.77）% and （11.77±0.58）%, and the difference was statistically significant compared with the control （[6.64±0.191%, P〈0.01）. The expression of Cox-2 mRNA in the ART group was lower than those of control group, yet the expression of Caspase-3 and E-Cadherin mRNA in the ART group was higher than those of control group. Conclusion： ART can inhibit HEC-1B cell growth and proliferation in a dose- and time-dependent manner. Furthermore, ART can induce apoptosis in a dose-dependent manner. ART is able to downregulate Cox-2 mRNA expression and to upregulate E-Cadherin and Caspase-3 mRNA expression. So we can conclude that ART could induce the endometrial carcinoma HEC-1B cell apoptosis and inhibit tumor cell proliferation.
文摘Locally recurrent head and neck squamous cell carcinoma(HNSCC)is often unresectable,and a repeat course of radiotherapy is associated with incremental toxicities.Boron neutron capture therapy(BNCT)is a novel targeted radiotherapy modality that can achieve a high dose gradient between cancerous and adjacent normal tissues.However,the relationships among the dose resulting from BNCT,tumor response to BNCT,and survival are not completely understood.Recently,a study published in Radiotherapy and Oncology investigated the efficacy of BNCT in the treatment of patients with locally recurrent HNSCC and the factors associated with favorable treatment response and survival.In this article,the findings,strengths and limitations of this study are discussed in depth,and the significance of the study and motivations for future research are highlighted.
文摘Synchronous bilateral multiple chromophobe cell renal carcinoma is rare; here we report a case diagnosed with bilateral renal multiple tumors complicated with a cyst in the right kidney. Retroperitoneal laparoscopic bilateral nephron sparing surgery was performed and there was no serious postoperative renal dysfunction. Pathological and immunohistochemical diagnoses of both tumors were chromophobe cell renal carcinoma. The patient has been doing well without any evidence of recurrence or metastasis for 6 months.
文摘Objective To evaluate the application of weak cation exchange (WCX) magnetic bead-based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in detecting differentially expressed proteins in the urine of renal clear cell carcinoma (RCCC) and its value in the early diagnosis of RCCC.Methods Eleven newly diagnosed patients (10 males and 1 female, aged 46-78, mean 63 years) of renal clear cell carcinoma by biopsy and 10 healthy volunteers (all males, aged 25-32, mean 29.7 years) were enrolled in this study. Urine samples of the RCCC patients and healthy controls were collected in the morning.Weak cation exchange (WCX) bead-based MALDI-TOF MS technique was applied in detecting differential protein peaks in the urine of RCCC. ClinProTools2.2 software was utilized to determine the characteristic proteins in the urine of RCCC patients for the predictive model of RCCC.Results The technique identified 160 protein peaks in the urine that were different between RCCC patients and health controls; and among them, there was one peak (molecular weight of 2221.71 Da) with statistical significance (P=0.0304). With genetic algorithms and the support vector machine, we screened out 13 characteristic protein peaks for the predictive model.Conclusions The application of WCX magnetic bead-based MALDI-TOF MS in detecting differentiallyexpressed proteins in urine may have potential value for the early diagnosis of RCCC.
文摘This article reports a case of simultaneous occurrence of 2 primary renal tumors of different histology, a transitional cell carcinoma and a renal cell carcinoma. in the same kidney. The histological, immunohistochemical and ultrastructural changes of the tumors were described. A review of the literature to date revealed this case to be rare. only 24 other cases were reported previously.
文摘Objective:To analyze the p16INK4a genomic alteration and expression status in 3 human pancreatic carcinoma cell lines with different potential of metastasis. Methods:Using PCR-SSCP, Dot-blot and immunohistochemistry, the p16INK4a genomic mutation and expression were analyzed on DNA, mRNA and protein levels in 3 human pancreatic carcinoma cell lines Patu8902, Patu8988 and SW1990, which had different potential of metastasis. Results: (1) On DNA level: there was no deletion of p16INK4a Exon Ⅰ in 3cell lines; p16INK4a Exon Ⅱ was only deleted in Patu8902 while no deletion in Patu8988 and SW1990. No insertion, microdeletion and point mutation were found in the 3 cell lines. (2) On RNA level: the expression of p16INK4a protein was negative in Patu8902, low expressed in SW1990, but highly expressed in Patu8988.(3) On protein level: P16 protein was strongly stained in Patu8988, much lower in SW1990, but not stained in Patu8902. Conclusion:The genomic type and expression of p16INK4a are quite different in 3 pancreatic carcinoma cell lines which have different potential of metastasis. It is suggested that genomic homozygous deletion and low expression of mRNA might relate to the potential of metastasis of pancreatic cell lines. In other words, dysfunction of p16INK4a might be an important mechanism in the metastasis of pancreatic carcinoma.
文摘The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.
文摘This study was aimed at providing an experimental model for the research of HCC. Twelve specimens that were pathologically identified as HCC were cultured in vitro . To investigate their biological characteristics, the survived cells were morphologically
文摘Objective: To study the effect of 5-Aza-2’ -deoxycytidine (5-Aza-cdR) on tumour suppressor gene p16 expres- sion in hepatocellular carcinoma cells. Method: Expression of pl6 mRNA and protein in hepatocellular carcinoma cell lines SMMC-7721 and HePG2 before and after treatment with 5-Aza-cdR were analyzed via reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemistrty Results: The expression levels of p16 mRNA and protein were increased dramatically after treatment with 5-Aza-cdR. Conclusion: Our data show that, 5-Aza-2’ -deoxycytidine can increase the expression of pl6 gene both at transcription and translation. The findings suggested that 5-Aza-cdR may reactivate the pl6 gene by demethylation.
文摘The effects of two antisense oligodeoxynucleotides on the expression of c-Ha-ras proto-oncogene and the growth of human gastric carcinoma cell lines were observed. Synthetic 15-mer directed at the region of the translational initiation site of c-Ha-ras proto-oncogene (ASO-r) greatly inhibited the proliferation (55. 61%,P<0. 05) and DNA synthesis (76. 79%,P<0. 05) of MGc-803 cell line. It also inhibited the proliferation (62. 02%,P<0. 05) and DNA synthesis (76. 78%, P<0. 05) of SGc-7901 cell line. A reduction in intracellular P21 ras protein levels in MGc-803 cell line was observed 6 h after the treatment with ASO-r and maintained over 12 h. Another synthetic 15-mer targeted against the initiation codon and downstream 4 codons of c-myc proto-oncogene (ASOm) inhibited only DNA synthesis of MGc-803 cell line (71. 37%, P<0. 05). The control 15-mer did not inhibit the expression of P21 protein and proliferation of these cell lines. These experiments seemed to provide evidence that ASO-r could be effective in inhibiting the expression of c-Ha-ras proto-oncogene and controlling the growth of human gastric carcinoma cells,and that the over-expression of c-Ha-ras proto-oncogene might mainly be associated with the malignant proliferation of human gastric carcinoma cells.
