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Background:Gastrointestinal carcinoids are prone to be neglected in clinical practice because of the poor specific symptoms in early stage. Aims:To analyze the clinicopathological characteristics,treatment modalities and prognosis of a series of cases of gastrointestinal carcinoids for strengthening the understanding of the disease. Methods:A total of 116 patients diagnosed as gastrointestinal carcinoids by pathology from Jan. 1997 to Jan. 2010 in 8 hospitals at Wuhan were enrolled in this retrospective study. Data on sex,age,major symptoms,diagnostic approaches,treatment modalities, pathological features and prognosis, etc. were collected and analyzed. Results:The most common sites of the gastrointestinal carcinoids were rectum(59. 5%)and stomach(19. 8%);the most common symptoms were abdominal pain,abdominal distention and hematochezia. The positivity rates of immunohistochemical marker NSE,Syn and CgA were 92. 7%,87. 5% and 62. 5%,respectively. The proportion of stomach carcinoids with diameter larger than 2 cm was 73. 9%, and that of rectal carcinoids was only 13. 0%(P 0. 05). Conclusions:Gastrointestinal carcinoids enrolled in this study distributed mainly in rectum and stomach. As compared with rectal carcinoids,gastric carcinoids were more advanced in disease stage with poorer prognosis. Regular health checks, strengthening the understanding of the disease,and grasping the specificities of carcinoids distributed at different sites might be helpful for the early diagnosis and treatment of gastrointestinal carcinoids,thus improving the survival rate.
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Objective To explore the correlation between the psychological resilience levelwith the emotional regulation modeand personality characteristicin the patientwith gastricarcinomto provide the theoretical reference fothe intervention measure.MethodOne hundred and forty-seven patientwith gastricancewere selected athe research subject(gastricancegroup) and contemporaneou150 individualwith healthy physical examination in the outpatiendepartmenwere selected athe control group .The Connoand Davidson Resilience Scale(CD-RISC) ,Eysenck Personality Questionnaire(EPQ) and Emotion Regu-lation Scale were adopted to perform the investigation .The correlation between the psychological resilience levelwith the emotional regulation modeand personality characteristicwaanalyzed .ResultThe overall CD-RISscore in the gastricancegroup wa(59 .12 ± 9 .19) point,which belonged to the poorescope ;the personality characteristic,emotional regulation modeand psycho-logical resilience had statistical differencebetween the gastricancegroup and the control group (P＜0 .05);the multivariate Lo-gistiregression analysiresultshowed thathe introversion ,extroversion ,neuroticism ,catharsiregulation and depression regula-tion had largeinfluence on the lowepsychological resilience level in the patientwith gastricance(P＜0 .05);the psychological resilience in the patientwith gastricancewapositively correlated with the catharsiregulation and the depression regulation (r=0 .287 ,0 .136 ,P＜0 .05) and negatively correlated with the introversion ,extroversion and neuroticism (r= -0 .232 ,-0 .789 , P＜0 .05) .Conclusion The introversion ,extroversion ,neuroticism ,catharsiregulation and depression regulation are the importanfactorinfluencing the psychological resilience level .The multi-angle interventional measureshould be taken to improve the psy-chological resilience level in the patientwith gastricance.
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Objective To analyze and explore the clinical features,pathological characters,treatment and prognosis of rectum carcinoid.Methods From January 1997 to January 2010,69 pathologically diagnosed rectum carcinoid cases were collected from Union Hospital of Tongji Medical College,Huazhong University of Science and Technology and other 7 hospitals.The clinical features,pathological characters,treatment and prognosis were analyzed. Results Of 69 rectum carconid cases,there were 36 males and 33 females.The average age was (49.3±12.9) years.The common symptom were hemotochezia,abdominal pain,constipation,diarrhoea and abdominal distension.There were 55 cases with lesions from the anus less than 8 cm and in other patients,lesions from the anus were all more than 8 cm.66 cases were typical carcinoid,3 cases were atypical carcinoid.40 cases underwent the immunohistochemical staining.The common markers for immunohistochemical staining were Syn,CgA and NSE,the positive percentage were 90％ (36/40),75％ (30/40) and 82.5％(33/40) respectively.A total of 24 patients received endoscopic therapy,44 patients had surgery,1 patient who refused surgery received only life support and symptomatic treatment.Conclusion No specific clinical symptoms of rectum carcinoid,and most were typical carcinoid.Lesions confined to mucosa and submucosa could be considered the endoscopic therapy.
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An 18-year-old female presented with painful erythema and nodules on both legs for more than 2 years.Dermatological examination showed irregularly sized,mildly indurated,tender,deep subcutaneous nodules arising in diffused infiltrated dark erythematous patches in the inner and posterior region of the left leg.Histopathology showed no significant changes in the epidermis.There were perivascular lymphoid cell infiltrates in the dermis and subcutis.Multiple sites of necrosis of blood vessel walls with vascular occlusions were noted.The lumens of some blood vessels were filled with lymphocytes,among which were many atypical cells with hyperchromatic nuclei and pathologic mitotic figures.Immunohistochemistry showed that lymphocytes in the cavities of blood vessels were positive for CD3(+++),CD3ε(+++),CD2(+),CD56(+++),granzyme B(+++),perforin(+++),CD30(+),Ki67 (+++,100％ ),but negative for CD20,CD5,CD7,CD4,CD8,TdT,anaplastic lymphoma kinase,early membrane antigen (EMA) or pan cytokeratin (pCK).The endothelial cells lining the blood vessels stained positively for CD34.The intravascular lymphocytes were also positive for EBER1/2 by in situ hybridization.A diagnosis of cutaneous intravascular NK/T cell lymphoma was made.
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The effect of Smac gene on the TRAIL-induced apoptosis of the prostate cancer cell line PC-3 and the molecular mechanism were investigated. The Smac gene was transfected into PC-3 cells under the induction of liposome. The intrinsic Smac gene expression was detected by Western blotting. After treatment with TRAIL as an apoptosis inducer, in vitro cell growth activity was assayed by MTT colorimetry. The apoptosis rate of PC-3 cells was determined by annexin V-FITC and propidium iodide staining flow cytometry. The expression of cellular XIAP and caspase-3 genes was examined by Western blotting. Smac-transfected cells (PC-3/Smac group) had significantly increased Smac protein level as compared with PC-3 controls (P<0.01). After induction with 100-200 ng/mL TRAIL for 12-36 h, cellular proliferation rate in PC-3/Smac group was significantly lower than in PC-3 controls (P<0.05). After induction with 100 ng/mL TRAIL for 24 h, the apoptosis rate in PC-3/Smac group was significantly enhanced as compared with that of PC-3 controls (P<0.05). Accordingly, the XIAP expression level was down-regulated significantly (P<0.05) and caspase-3 subunit P20 was up-regulated significantly (P<0.05). It is suggested that the over-expression of cellular Smac can inhibit inhibitor of apoptosis proteins (IAPs), enhance caspases activity and the apoptosis rate of PC-3 cells induced by TRAIL, which may provide a useful experimental basis for prostate cancer therapy.
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A 20-year-old male patient presented with myalgia of upper limbs and myasthenia of extremities for more than 1 month. Physical examination showed diffuse erythema on the cheeks, upper eyelids, upper chest, neck and dorsa of the hands. The myodynamia of the proximal and distal muscles of upper and lower extremities was grade Ⅳ, Ⅴ, Ⅲ and Ⅴ respectively. Laboratory examinations revealed that the serum levels of creatine kinase, CK-MB and lactate dehydrogenase were 2103 U/L, 83 U/L and 489 U/L respectively, which were all above the normal range. Electromyogram revealed myopathic abnormality and normal nerve conduction velocity. Histopathology of gastrocnemius muscle showed hypertrophy and swelling of muscle fibers, disappearance or fuzziness of transverse striation, and intermuscular lymphoid cell infiltration. A biopsy of the skin lesion from the upper chest showed liquefaction degeneration of and colloid bodies in basal cell layer, perivascular lymphoid cell infiltration in the dermis. A diagnosis of dermatomyositis was established based on the clinical and laboratory findings. After management with intravenous prednisolone 80 mg once daily and symptomatic treatment for 4 weeks, the myodynamia of upper limbs was improved, serum levels of creatine kinase,CK-MB and lactate dehydrogenase reached the normal ranges. However, the myodynamia of lower limbs progressively deteriorated with the emergence of paresthesia. Enhanced MRI scan showed a tumor in the vertebral canal at the level of thoracic vertebra 11 to 12. A spherical encapsulated tumor measuring 3 cm in diameter was surgically removed. The tumor was diagnosed as paraganglioma in vertebral canal according to pathological and immunohistochemical findings. The patient was finally diagnosed with paraganglioma in vertebral canal superimposed on dermatomyositis.
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In our previous study, we identified a novel testis-specific expressed gene 2 (TSEG-2) from mouse testis. To further investigate its functions, 35 male Balb/c mice (8 weeks old) were divided into cryptorchidism group (n=20), sham group (n=10), and control group (n=5). In cryptorchidism group, the right testes were anchored to the inner lateral abdominal wall. In situ hybridization (ISH) was applied to measure the localization of TSEG-2 in mouse testis. Real-time quantitative PCR was performed to detect the expression of TSEG-2 gene. Meanwhile, under the mediation of polyethylenimine (PEI), the recombinant vector pEGFP-TSEG-2 (n=5) or empty vector (mock, n=5) was transfected into the testis of male mice. The transfection efficiencies were measured under a fluorescence microscope. The apoptosis of spermatogenic cells was detected by terminal deoxynuleotidyl-mediated nick end labeling (TUNEL). The results showed that TSEG-2 was expressed in convoluted seminiferous tubules, more precisely, in spermatogonia and spermatocytes. As compared with sham and control groups, the TSEG-2 transcription was significantly enhanced (P<0.05) and was correlated with apoptosis of spermatogenic cells in cryptorchid testes (P<0.05). PEI was efficient in mediating transfection of TSEG-2 into seminiferous tubules of testis. One week post-transfection, intratesticular injection of TSEG-2 resulted in increased apoptosis of spermatogenic cells in vivo (P<0.05). These results indicate that TSEG-2 may participate in the apoptosis of spermatogenic cells and the pathogenesis of cryptorchidism.
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Objective To investigate the clinical characteristics of primary gastrointestinal lymphoma (PGIL) on different origin site in order to improve its diagnosis.Methods The clinical data from 202 patients with PGIL diagnosed by histology from January 1999 to June 2007 were identified from the clinical databases of 8 hospitals in Wuhan area and retrospectively analyzed.The patients were divided into gastric,small intestinal and large intestinal lymphoma groups according to the site of origin and there clinical characteristics were compared.Results The PGIL localization was gastric in 113 (56.0%) cases, small intestine in 37(18.3%) cases and large intestine in 52 (25.7%) cases.One hundred and thirty (64.4%) were males and 72 (35.6%) were females.The male patients were predominant.The median duration of symptoms in gastric lymphoma group was longer than small intestinal lymphoma group (3.0 months vs.1.0 month,P=0.013).The most common symptoms were abdominal pain and anemia. The clinical stage was Ⅰ E and Ⅱ E in 71.3% of cases.The large intestinal lymphoma group presented more advanced-stage disease compared with gastric lymphoma group (P = 0.014).The frequent histological type was mucosa-associated lymphoid tissue lymphoma (MALT),diffuse large B-cell lymphoma and T-cell lymphoma.Gastric,small intestinal and large intestinal lymphomas presented more frequently as low-grade MALT lymphoma (56.9%),T-cell lymphoma (34.4%) and high-grade B-cell lymphoma (51.1%),respectively (all P value ＜0.05).The common macroscopic type of PGIL were nodular protruding and ulcerative type.Compared with gastric lymphoma,nodular protruding type was more common and ulcerative type was less common in large intestinal lymphoma (P = 0.000).The diagnosis confirmed by endoscopic biopsy were 58.7% (61/104),25.0% (4/16),48.2% (13/27) in gastric,small intestinal and large intestinal lymphoma groups,respectively.Conclusions The clinical characteristics are different in patients with different localization of PGIL including patient characters, initial symptoms,histological classification,clinical stage,macroscopic feature,endoscopic findings. Analysis of these clinical characteristics is helpful to improve its diagnosis.
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The expression of X-linked inhibitor of apoptosis protein (XIAP) gene and its effect on chemotherapeutic sensitivity in bladder carcinoma was explored. By using immunohistochemistry,the expression of XIAP was detected in 47 bladder carcinomas and 5 normal bladder tissues. The XIAP gene was transfected into bladder cancer cell line T24 by liposome and the positive clone was screened by G418. Cellular XIAP mRNA level was detected by RT-PCR. Low-dose mitocycin C was administered to induce the apoptosis of T24 cells. The in vitro growth of bladder carcinoma cells was analyzed by MTT colorimetry, and the apoptosis rate was assayed by TUNEL methods. It was found XIAP was moderately expressed in bladder carcinomas with the the positive rate being 78.73% (37/47), but the positive rate was not correlated with carcinoma stages and grades (P＜0.05). XIAP mRNA level in transfected T24 cells was significantly increased by 3.8 times as compared with that in the cells not transfected with XIAP. After treatment with low-dose mitomycin C (0.005 and 0.05 mg/mL), the growth rate in XIAP no-transfected control group was increased by (11.60±0.25)% and (16.51±0.87)% (P＜0.05), and the apoptosis rate was decreased by (10.1±0.2)% and (11.9±0.2%) (P＜0.05) respectively as compared with XIAP transfected group. It was concluded that XIAP was expressed in most of bladder carcimoma samples. Overexpression of XIAP in T24 could significantly reduce the MMC-induced apoptosis of bladder carcinoma, suggesting its effect on the chemotherapeutic sensitivity of T24 cells.
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The expression of X-linked inhibitor of apoptosis protein (XIAP) gene and its effect on chemotherapeutic sensitivity in bladder carcinoma was explored. By using immunohistochemistry, the expression of XIAP was detected in 47 bladder carcinomas and 5 normal bladder tissues. The XIAP gene was transfected into bladder cancer cell line T24 by liposome and the positive clone was screened by G418. Cellular XIAP mRNA level was detected by RT-PCR. Low-dose mitomycin C was administered to induce the apoptosis of T24 cells. The in vitro growth of bladder carcinoma cells was analyzed by MTT colorimetry, and the apoptosis rate was assayed by TUNEL methods. It was found XIAP was moderately expressed in bladder carcinomas with the the positive rate being 78.73% (37/47), but the positive rate was not correlated with carcinoma stages and grades (P<0.05). XIAP mRNA level in transfected T24 cells was significantly increased by 3.8 times as compared with that in the cells not transfected with XIAP. After treatment with low-dose mitomycin C (0.005 and 0.05 mg/mL), the growth rate in XIAP no-transfected control group was increased by (11.60+/-0.25)% and (16.51+/-0.87)% (P<0.05), and the apoptosis rate was decreased by (10.1+/-0.2)% and (11.9+/-0.2%) (P<0.05) respectively as compared with XIAP transfected group. It was concluded that XIAP was expressed in most of bladder carcinoma samples. Overexpression of XIAP in T24 could significantly reduce the MMC-induced apoptosis of bladder carcinoma, suggesting its effect on the chemotherapeutic sensitivity of T24 cells.
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The enhancing effects of Smac gene on the mitomycin C-induced apoptosis of the bladder cancer cell line T24 were investigated. The Smac gene was transfected into bladder cancer cell line T24 under the induction of liposome. The intrinsic Smac level was detected by using immunohistochemistry and RT-PCR. The in vitro cellular growth activities were assayed by MTT colorimetry.Apoptosis was assayed by the flow cytometry. The results showed that as compared with the control cells, the apoptosis rate of T24 cells induced by mitomycin C was enhanced by transfected Smac gene. Flow cytometry revealed that, the apoptosis rate was 18.84% and 33.52%, and 10.72% and 26.24% respectively in blank and transfected cells treated with 0.05 or 0.005 mg/mL mitomycin C (P＜0.05). It was concluded that Smac could enhance the apoptosis of T24 by mitomycin C,which could provide a useful experimental evidence for bladder cancer therapy.
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The enhancing effects of Smac gene on the mitomycin C-induced apoptosis of the bladder cancer cell line T24 were investigated. The Smac gene was transfected into bladder cancer cell line T24 under the induction of liposome. The intrinsic Smac level was detected by using immunohistochemistry and RT-PCR. The in vitro cellular growth activities were assayed by MTT colorimetry. Apoptosis was assayed by the flow cytometry. The results showed that as compared with the control cells, the apoptosis rate of T24 cells induced by mitomycin C was enhanced by transfected Smac gene. Flow cytometry revealed that, the apoptosis rate was 18.84% and 33.52%, and 10.72% and 26.24% respectively in blank and transfected cells treated with 0.05 or 0.005 mg/mL mitomycin C (P < 0.05). It was concluded that Smac could enhance the apoptosis of T24 by mitomycin C, which could provide a useful experimental evidence for bladder cancer therapy.
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The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6-24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 μmol/L- 40 μmol/L NVC and NGC for 6 - 24 h, the growth inhibitory effects on EJ cells were 6.71% -65.13 % (P＜0.05), 10.96 % -73.01% (P ＜0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P＜0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumortargeted chemotherapeutic drugs.
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To clone Uroplakin Ⅱ gene from Chinese transitional cell carcinoma (TCC) of bladder and construct its eukaryotic expression vector, the molecular cloning method was used to extract total RNA from a GⅢ/ T3N0M0 tissue sample of the bladder TCC patients. The primers were designed by Primer 5.0 software. Full length cDNA of Uroplakin Ⅱ gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), assayed by nucleic acid sequencing and then inserted between Xba Ⅰ and HindⅢ restrictive sites of eukaryotic expression vector pcDNA3.0. The recombinant was assayed by restricted enzyme digestion. Under the induction of Lipofectamine 2000, the recombinant was transfected into Uroplakin Ⅱ negative bladder cancer cell line EJ. Cellular expression levels of Uroplakin Ⅱ were detected by RT-PCR. The nucleic acid sequencing results indicated that Chinese Uroplakin Ⅱ cDNA (555 bp) was successfully cloned. The BLAST analysis demonstrated that the cloned sequence is 100 % homologous with sequences reported overseas. The GenBank accession number AY455312 was also registered. The results of restricted enzyme digestion indicated that eukaryotic vector pcDNA-UP Ⅱ for Uroplakin Ⅱ was successfully constructed.After being transferred with pcDNA-UPⅡ for 72 h, cellular Uroplakin Ⅱ mRNA levels were significantly improved (P＜0.01). It is concluded that human Uroplakin Ⅱ gene was successfully cloned from Chinese TCC tissues, which provided a basis for further exploration of the roles of Uroplakin Ⅱ gene in TCC biological behaviors and potential strategies for targeted biological therapy of TCC.
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The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6 - 24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 micromol/L - 40 micromol/L NVC and NGC for 6 - 24 h, the growth inhibitory effects on EJ cells were 6.71% - 65.13% (P < 0.05), 10.96% - 73.01% (P < 0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P < 0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumor-targeted chemotherapeutic drugs.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Curcumin/pharmacology , Dose-Response Relationship, Drug , Prodrugs/chemical synthesis , Prodrugs/pharmacology , Tumor Cells, Cultured , Urinary Bladder Neoplasms/pathologyABSTRACT
To study the growth-inhibitory effects of curcumin on human ovary cancer A2780 cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780 cancer cells, after being treated with 10 micromol/L-50 micromol/L curcumin for 6-24 h, were examined by MTT method. The morphological changes of cancer cells were observed under inversion microscopy. Cellular apoptotic rates were determined by using TUNEL. The protein expression levels of bcl-2, p53 and MDM2 in cancer cells were examined by SP immunohistochemistry. After being treated by various concentrations of curcumin, the growth of cancer cells was inhibited significantly. Some cancer cells presented characteristic morphological changes of apoptosis. The rates of apoptosis were 6.41%-28.48% (P<0.01). The expression of bcl-2 and p53 was decreased, which depended on the action time (P<0.01). There were no obvious changes in MDM2 expression. It was concluded that curcumin could significantly inhibit the growth of ovary cancer cells. The induction of apoptosis by down-regulating the expression of bcl-2 and p53 was probably one of its molecular mechanisms.
Subject(s)
Female , Humans , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Cell Division , Curcuma , Chemistry , Curcumin , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Nuclear Proteins , Metabolism , Ovarian Neoplasms , Pathology , Proto-Oncogene Proteins , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Proto-Oncogene Proteins c-mdm2 , Tumor Cells, Cultured , Tumor Suppressor Protein p53 , MetabolismABSTRACT
The resistin-like molecules(RELMs)are a novel protein family with tissue-specific distribution.Recent evidences suggest their important roles in type II diabetes mellitus,inflammation,immunological reactions and cell proliferation,which provoked many interests for the researchers.This overview summarizes the structure,tissue distribution,biological functions,regulatory pathways,and their relationship with diseases of these family members.
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Aim To explore the growth inhibition effects of jasmonates on human neuroblastoma SH-SY5Y cell line,and to investigate its mechanisms.Methods After administration of 0.5~2.5 mmol?L-1 jasmonates for 6~24 hrs, the growth inhibition rates of SH-SY5Y cells were studied by MTT colorimetry.Cell cycle phases were assayed by propidium iodide staining flow cytometry. Cellular apoptosis was inspected by Hoechst 33258 fluorescent staining and Annexin V-FITC and propidium iodide staining flow cytometry.Gene expressions of PCNA, cyclin D1 and N-myc were determined by reverse transcription polymerase chain reaction.Results Jasmonates inhibited the growth of SH-SY5Y cells in a dose-and time-dependent manner,while the methyl jasmonate was the most efficient. After administration of 0.5 to 2.5 mmol?L-1 of methyl jasmonate for 24 hrs,the growth inhibition rates of cells reached 5.75%~88.7%(P