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1.
Ann Hematol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105740

RESUMO

Chronic neutrophil leukemia (CNL) is a rare and life-threatening disease. Cases of CNL combined with lymphoma are rare. Here, we report a case of CNL with T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in a 28-year-old male. After a regimen of ruxolitinib, VICLP (Vincristine, Idarubicin, Cyclophosphamide, Prednisone, Peg-asparaginase) regimen, high-dose cytarabine, and methotrexate regimens, the patient's bone marrow condition partially resolved. However, when the disease relapsed four months later, despite attempts with selinexor, venetoclax, and CAG(aclarubicin hydrochloride, Algocytidine, Granulocyte Stimulating Factor) chemotherapy, the leukocytes and peripheral blood primitive cells reduced, but the bone marrow did not achieve remission. This pathogenesis may be related to microenvironmental immune escape under prolonged inflammatory stimulation and gene disruption affecting protein function due to colony-stimulating factor 3 receptor gene (CSF3R) mutations. For this type of disease, early intervention may delay disease progression.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 308-312, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387940

RESUMO

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with splenomegaly as the major clinical manifestation, which is commonly considered to be linked to splenic extramedullary hematopoiesis. Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly. With the application of JAK1/2 inhibitors in clinical, the symptoms of splenomegaly have been significantly improved in PMF patients. This article will review the pathogenesis and targeted treatment progress of splenomegaly in PMF.


Assuntos
Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Esplenomegalia/complicações , Esplenomegalia/patologia , Esplenomegalia/terapia , Mielofibrose Primária/terapia , Medula Óssea/metabolismo , Baço , Células-Tronco Hematopoéticas , Inibidores de Janus Quinases/metabolismo
3.
Curr Med Sci ; 43(3): 539-550, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37119369

RESUMO

OBJECTIVE: This study aimed to explore the value of M701, targeting epithelial cell adhesion molecule (EpCAM) and CD3, in the immunotherapy of ovarian cancer ascites by the in vitro assay. METHODS: The expression of EpCAM in ovarian cancer tissues was analyzed by databases. The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry. The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay. The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens. Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells. RESULTS: The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue. The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites. The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells. M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites. M701 could mediate the binding of CD3+ T cells to EpCAM+ tumor cells and induce T cell activation in a dose-dependent manner. CONCLUSION: M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites, which had a promising application in immunotherapy for patients with ovarian cancer ascites.


Assuntos
Anticorpos Biespecíficos , Neoplasias Ovarianas , Feminino , Humanos , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Ascite , Moléculas de Adesão Celular/genética , Antígenos de Neoplasias , Apoptose , Linhagem Celular Tumoral , Anticorpos Biespecíficos/farmacologia , Imunoterapia/métodos
4.
Hum Reprod ; 37(12): 2856-2866, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36223608

RESUMO

STUDY QUESTION: Would the construction of a competing endogenous RNA (ceRNA) network help identify new drug targets for the development of potential therapies for polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Both Food and Drug Administartion (FDA)-approved and candidate drugs could be identified by combining bioinformatics approaches with clinical sample analysis based on our established ceRNA network. WHAT IS KNOWN ALREADY: Thus far, no effective drugs are available for treating PCOS. ceRNAs play crucial roles in multiple diseases, and some of them are in current use as prognostic biomarkers as well as for chemo-response and drug prediction. STUDY DESIGN, SIZE, DURATION: For the bioinformatics part, five microarrays of human granulosa cells were considered eligible after applying strict screening criteria and were used to construct the ceRNA network for target identification. For population-based validation, samples from 24 women with and without PCOS were collected from January 2021 to July 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The public data included 27 unaffected women and 25 women with PCOS, according to the Rotterdam criteria proposed in 2003. The limma and RobustRankAggreg R packages were used to identify differentially expressed messenger RNAs and noncoding RNAs. Gene Ontology, Reactome and Kyoto Encyclopedia of Genes and Gemomes (KEGG) enrichment analyses were performed. A ceRNA network was constructed by integrating the differentially expressed genes and target genes. The population-based validation included human luteinized granulosa cell samples from 12 unaffected women and 12 women with PCOS. Quantitative real-time polymerase chain reaction was conducted to detect the levels of mRNAs and microRNAs (miRNAs). Connectivity map and computational model algorithms were implemented to predict therapeutic drugs from the ceRNA network. Additionally, we compared the predicted drugs with known clinical medications in DrugBank. MAIN RESULTS AND THE ROLE OF CHANCE: A set of 10 mRNAs, 11 miRNAs and 53 long non-coding RNAs (lncRNAs) were differentially expressed. Functional enrichment analysis revealed the highest relevance to immune system-related biological processes and signalling pathways, such as cytokine secretion and leucocyte chemotaxis. A ceRNA consisting of two lncRNAs, two miRNAs and five mRNAs was constructed. Through network construction via bioinformatic analysis, we identified some already approved drugs (such as metformin) that could target some molecules in the network as potential drug candidates for PCOS. LARGE SCALE DATA: Public sequencing data were obtained from GSE34526, GSE84376, GSE102293, GSE106724 and GSE114419, which have been deposited in the Gene Expression Omnibus database. LIMITATIONS, REASONS FOR CAUTION: Experiments, such as immunoprecipitation, luciferase reporter assays and animal model studies, are needed to validate the potential targets in the ceRNA network before the identified drug candidates can be tested using cellular and animal model systems. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide new bioinformatic insight into the possible pathogenesis of PCOS from ceRNA network analysis, which has not been previously studied in the human reproductive field. Our study also reveals some potential drug candidates for the future development of possible therapies against PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development Program of China (2021YFC2700400) and the National Natural Science Foundation of China (82001498). The authors have no conflicts of interest to disclose.


Assuntos
MicroRNAs , Síndrome do Ovário Policístico , RNA Longo não Codificante , Animais , Humanos , Feminino , RNA Longo não Codificante/genética , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 959-964, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680834

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by uncontrolled proliferation of activated macrophage, and secreting high amounts of inflammatory cytokines which lead to multi-organ dysfunction syndrome. HLH patients often show different clinical characteristics during the disease was progressed, in which coagulopathy were the most common, including thrombocytopenia and hypofibrinogenemia, those are the major cause of death in patients, and the clinicians should increase awareness of the mechanisms, clinical characteristics, prognosis and treatment. In this review, the above problems are briefly summarized, to deepen understanding of the HLH related coagulation dysfunctions, and early identification and treatment to reduce mortality, so as to provide more opportunities for HLH patients to recieve subsequent treatment.


Assuntos
Afibrinogenemia , Transtornos da Coagulação Sanguínea , Linfo-Histiocitose Hemofagocítica , Trombocitopenia , Transtornos da Coagulação Sanguínea/terapia , Humanos , Linfo-Histiocitose Hemofagocítica/terapia , Prognóstico
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1671-1675, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627460

RESUMO

Chronic lymphocytic leukemia (CLL) patients usually show immune dysfunction, which often leads to autoimmune hemocytopenia. Immune thrombocytopenia (ITP) is one of the common complications. The pathogenesis of CLL-related ITP is complex and has not been fully elucidated. At present, the researches mainly focus on humoral immunity, cellular immunity and innate immune disorders. Recent studies suggest that genomic abnormalities and microRNAs are also involved in CLL-related ITP. Traditional ITP standard therapy has a poor effect on CLL-related ITP. Chemotherapy or monoclonal antibody therapy against the primary pathogenesis of CLL can effectively treat thrombocytopenia, and the emergence of new targeted drugs also provides new treatment options for the disease. In this paper, the progresses of CLL-related ITP pathogenesis, prognosis and treatment in recent years are reviewed.


Assuntos
Leucemia Linfocítica Crônica de Células B , MicroRNAs , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Anticorpos Monoclonais , Humanos , Leucemia Linfocítica Crônica de Células B/complicações
7.
Curr Med Sci ; 41(2): 342-347, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877552

RESUMO

Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect young females. To date, there have been few studies on YSTs. We evaluated the relationship between clinicopathologic characteristics of patients with ovarian YSTs and disease outcome based on Surveillance, Epidemiology, and End Results data. The Kaplan-Meier method and log-rank test were used to evaluate differences in survival rates. Data for 269 patients were analyzed. The incidence of YSTs among ovarian germ cell tumors (OGCTs) cases was 0.4%; median patient age was 22.0 years, and most tumors were unilateral. Patients presented with distant metastasis (37.5%), localized disease (49.1%), and regional spread (8.9%). American Joint Committee on Cancer stage was available for 13 patients (stage IA, n=2; stage IC, n=1; stage IIIA, n=1; stage IIIB, n=3; stage IIIC, n=2; and stage IV, n=4). Survival rates at 1, 3, and 5 years were 91.0%, 84.0%, and 83.2%, respectively, for overall survival (OS) and 92.0%, 85.4%, and 84.5%, respectively, for disease-specific survival (DSS). The 5-year OS and DSS of patients with ovary tumors were 91.5% and 92.9%, respectively, compared to 74.8% and 77.2%, respectively, for those with extra-ovarian spread (P<.001 for both OS and DSS). Age >50 years was associated with shorter OS and DSS (both P<0.001), whereas no associatios of OS and DSS were observed with pathologic grade (P=0.49 for OS and 0.52 for DSS). In summary, YSTs are typically unilateral, of a high grade, and localized to the ovary; extra-ovarian spread has a poor outcome, and postmenopausal women have worse prognosis than premenopausal women.


Assuntos
Tumor do Seio Endodérmico/epidemiologia , Tumor do Seio Endodérmico/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Fatores Etários , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Análise de Sobrevida
8.
Oncotarget ; 7(3): 3245-54, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26675546

RESUMO

Long-term outcome of high-grade serous epithelial ovarian carcinoma (HGSOC) remains poor as a result of recurrence and the emergence of drug resistance. Almost all the patients were given the same platinum-based chemotherapy after debulking surgery even though some of them are naturally resistant to the first-line chemotherapy. No method could verify this part of patients right after the surgery currently. In this study, we used 156 paraffin-embedded high-grade HGSOC specimens for immunohistochemical analysis with 37 immunology markers, and association between the expression levels of these markers and the chemoresponse were evaluated. A support vector machine (SVM)-based HGSOC prognostic classifier was then established, and was validated by a 95-patient independent cohort. The classifier was strongly predictive of chemotherapy resistance, and divided patients into low- and high-risk groups with significant differences progression-free survival (PFS) and overall survival (OS). This classifier may provide a potential way to predict the chemotherapy resistance of HGSOC right after the surgery, and then allow clinicians to make optimal clinical decision for those potentially chemoresistant patients. The potential clinical application of this classifier will benefit those patients with primary drug resistance.


Assuntos
Antineoplásicos/uso terapêutico , Técnicas de Apoio para a Decisão , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Critérios de Avaliação de Resposta em Tumores Sólidos , Máquina de Vetores de Suporte , Carcinoma Epitelial do Ovário , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia
9.
Asian Pac J Cancer Prev ; 16(9): 3773-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25987036

RESUMO

BACKGROUND: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. MATERIALS AND METHODS: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. RESULTS: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. CONCLUSIONS: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.


Assuntos
Carcinoma de Células Escamosas/secundário , Histerectomia/mortalidade , Excisão de Linfonodo/mortalidade , Nomogramas , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia
10.
J Huazhong Univ Sci Technolog Med Sci ; 34(5): 740-744, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25318886

RESUMO

To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Células HeLa , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismo
11.
J Huazhong Univ Sci Technolog Med Sci ; 34(2): 213-219, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24710935

RESUMO

Ovarian endometrioma is a common form of endometriosis, which may cause infertility, dysmenorrhea and pelvic pain in women of reproductive age. Although surgery is the treatment of choice for endometriomas, recurrence poses a formidable frustration. This study investigated potential risk factors of endometriomas recurrence, aiming to better understand its pathogenesis. A total of 307 patients with endometriomas were followed up for an average of 28.6 months and the 1-, 2- and 3-year cumulative recurrence rate was 9.5%, 21.9%, and 29.2%, respectively. Twenty-one potential risk factors for endometriomas recurrence were evaluated using Cox's proportional hazards models. Total revised American Fertility Society (rAFS) score was significantly associated with higher recurrence (OR=1.858, 95% CI=1.122-3.075, P=0.016), as well as younger age at surgery (OR=0.953, 95% CI=0.915-0.992, P=0.020). Semiradical surgical treatment was defined as surgical removal of cyst plus hysterectomy with preservation of bilateral or unilateral ovary, and was a significant factor that was associated with lower recurrence than the conservative surgery (OR=0.318, 95% CI=0.107-0.951, P=0.040). Postoperative pregnancy was favorable factors for disease recurrence (OR=0.217, 95% CI=0.102-0.460, P=0.000). The results suggest that endometrioma recurrence is inversely associated with age at surgery and postoperative pregnancy, and may correlate with total rAFS score and conservative surgery method.


Assuntos
Endometriose/patologia , Laparoscopia/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Fatores Etários , Endometriose/cirurgia , Feminino , Seguimentos , Humanos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Período Pós-Operatório , Gravidez , Modelos de Riscos Proporcionais , Fatores de Risco
12.
J Huazhong Univ Sci Technolog Med Sci ; 33(5): 735-742, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24142729

RESUMO

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.


Assuntos
Vacinas Anticâncer/imunologia , Papillomavirus Humano 16/imunologia , Proteínas Oncogênicas Virais/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Adulto , Idoso , Sequência de Aminoácidos , Animais , Vacinas Anticâncer/administração & dosagem , Linhagem Celular , Linhagem Celular Tumoral , Dependovirus/genética , Feminino , Regulação Viral da Expressão Gênica/imunologia , Vetores Genéticos/genética , Papillomavirus Humano 16/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/prevenção & controle , Neoplasias Experimentais/virologia , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Análise de Sobrevida , Linfócitos T/imunologia , Linfócitos T/metabolismo , Carga Tumoral/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia
13.
Acta Pharmacol Sin ; 34(4): 541-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23474708

RESUMO

AIM: Hec1, a member of the Ndc80 kinetochore complex, is highly expressed in cancers. The aim of this study was to explore the role and mechanism of action of Hec1 with respect to the cytotoxicity of paclitaxel in ovarian cancer. METHODS: Thirty ovarian cancer samples and 6 normal ovarian samples were collected. Hec1 expression in these samples was determined with immunohistochemistry. Ovarian cancer cell lines A2780, OV2008, C13K, SKOV3, and CAOV3 and A2780/Taxol were examined. Cell apoptosis and cell cycle analysis were detected with flow cytometric technique. siRNA was used to delete Hec1 in the cells. The expression of related mRNAs and proteins was measured using RT-PCR and Western blot analysis, respectively. RESULTS: Hec1 expression was significantly higher in ovarian cancer samples than in normal ovarian samples, and was associated with paclitaxel-resistance and poor prognosis. Among the 6 ovarian cancer cell lines examined, Hec1 expression was highest in paclitaxel-resistant A2780/Taxol cells, and lowest in A2780 cells. Depleting Hec1 in A2780/Taxol cells with siRNA decreased the IC50 value of paclitaxel by more than 10-fold (from 590±26.7 to 45.6±19.4 nmol/L). Depleting Hec1 in A2780 cells had no significant effect on the paclitaxel sensitivity. In paclitaxel-treated A2780/Taxol cells, depleting Hec1 significantly increased the cleaved PARP and Bax protein levels, and decreased the Bcl-xL protein level. CONCLUSION: Hec1 overexpression is associated with the progression and poor prognosis of ovarian cancer. Inhibition of Hec1 expression can sensitize ovarian cancer cells to paclitaxel.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/biossíntese , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proteínas do Citoesqueleto , Feminino , Humanos , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
14.
Zhonghua Zhong Liu Za Zhi ; 35(10): 737-41, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24378093

RESUMO

OBJECTIVE: Due to their lower risk for induction of resistance, antimicrobial peptides with selective anticancer effect could be developed into a new generation of anticancer drugs. We conjugated an antimicrobial peptide with tumor-targeting peptides (TMTP1) to explore whether it has inhibiting effect on the progression and metastasis of transplanted prostate cancer and gastric cancer in nude mice. METHODS: Subcutaneously transplanted human prostate cancer and orthotopically transplanted human gastric cancer in nude mice were prepared. 50 µmol/L PBS (control group), 50 µmol/L TMTP1 (TMTP1 group) or 50 µmol/L TMTP1-GG-D(KLAKLAK)(2) (treatment group) were injected i.p. to the three groups of nude mice, respectively. The binding ability of the novel fusion polypeptide TMTP1-GG-D(KLAKLAK)(2) to the tumors and its antitumor effect were assessed by measurement of tumor volume, histopathological examination of the tumor tissues, testing apoptosis index of tumor cells with TUNEL staining, and survival curve plotting of the mice. RESULTS: The median survival time of subcutaneous prostate cancer-bearing mice was 50 days in the control group, 55 days in the TMTP1 group, and 70 days in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.05). The median survival time of the subcutaneous gastric cancer-bearing mice was 25 days in the control group, 30 days in the TMTP1 group, and 45 days in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). The tumor volume in the subcutaneous prostate cancer-bearing mice was (2.5 ± 0.3)cm(3) in the control group, (1.8 ± 0.2) cm(3) in the TMTP1 group, and (0.3 ± 0.1)cm(3) in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). The tumor volume of the subcutaneous gastric cancer-bearing mice was (3.8 ± 0.4) cm(3) in the control group, (3.2 ± 0.2)cm(3) in the TMTP1 group, and (0.4 ± 0.1) cm(3) in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). Large tumors were observed in the stomach of the orthotopic gastric cancer-bearing mice of the control and TMTP1 groups. The tumor volume of the TMTP1-GG-D(KLAKLAK)(2) group was obviously reduced. White metastases in the liver, spleen and abdominal wall were observed in the control and TMTP1 groups (P < 0.01). TUNEL staining revealed that the apoptosis index of the control group was (31.9 ± 1.5)%, TMTP1 group (37.2 ± 2.3)% and TMTP1-GG-D(KLAKLAK)(2) group (69.7 ± 2.1)% (P < 0.01). CONCLUSIONS: The results of our study demonstrate that the novel fusion peptide of antimicriobial peptide conjugated with TMTP1 can effectively inhibit tumor progression and metastasis, therefore, is promising to be a novel effective anticancer drug.


Assuntos
Apoptose/efeitos dos fármacos , Oligopeptídeos/farmacologia , Peptídeos/farmacologia , Neoplasias da Próstata/patologia , Neoplasias Gástricas/patologia , Carga Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/secundário , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Esplênicas/secundário , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Asian Pac J Cancer Prev ; 13(10): 5299-302, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23244152

RESUMO

PURPOSE: To investigate the diet of patients with cervical cancer and precancerosis in the Wufeng area, a high- incidence region in China. METHODS: In the case group, 104 patients diagnosed with cervical cancer or cervical intraepithelial neoplasias (CINII/III) were recruited from the Wufeng area. Nine hundred thirty-six healthy women were selected from the same area as the matched controls. A questionnaire, which included questions about general lifestyle conditions, smoking and alcohol status, source of drinking water, green tea intake, and diet in the past year, was presented to all participants. RESULTS: Green tea intake (P=0.022, OR=0.551, 95% CI=0.330-0.919) and vegetable intake (P=0.035, OR=0.896, 95% CI=0.809-0.993) were identified as protective factors against cervical cancer or CINII/III. There was no indication of any associations of other lifestyle factors (smoking status, alcohol status, source of drinking water) or diet (intake of fruit, meat/egg/milk, soybean food, onion/garlic, staple food and pickled food) with cervical cancer. CONCLUSIONS: The results suggest that eating more fresh vegetables and drinking more green tea may help to reduce the risk of cervical cancer or CINII/III in people of the Wufeng area.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Dieta , Fumar/efeitos adversos , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Comportamento Alimentar , Feminino , Humanos , Incidência , Estilo de Vida , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Inquéritos e Questionários , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/etiologia , Displasia do Colo do Útero/prevenção & controle
16.
Zhonghua Yi Xue Za Zhi ; 92(28): 1954-8, 2012 Jul 24.
Artigo em Chinês | MEDLINE | ID: mdl-22944267

RESUMO

OBJECTIVE: To explore the expression and clinical significance of signal protein Sema4C in esophageal cancer, gastric cancer and rectal cancer. METHODS: Fifty esophageal cancer, 75 gastric cancer, 50 rectal cancer and 20 corresponding normal mucous membrane specimens, collected during the period of January 2008 to December 2010, were detected with streptavidin-peroxidase immunohistochemistry to detect the expression levels of Sema4C. And the relationships of the Sema4C expression with clinicopathological data was analyzed. RESULTS: The expression levels of Sema4C in three kinds of cancers were significantly higher than the corresponding normal mucous membranes (80.0% (n = 40) vs 20.0% (n = 4), 77.3% (n = 58) vs 25.0% (n = 5), 80.0% (n = 40) vs 15.0% (n = 3), all P = 0.000). Furthermore, the percentage of Sema4C positive cells was significantly higher in carcinoma nests of tumors with lymphatic metastasis than those without (90.3% (n = 28) vs 63.2% (n = 12), 85.0% (n = 51) vs 46.7% (n = 7), 92.0% (n = 23) vs 68.0% (n = 17), P = 0.049, 0.005, 0.034). However, no significant correlations were found between the Sema4C expression with gender, age, location of tumors, types of cancer cells, cell differentiation, tumor size, depth of invasion or tumor stage (all P > 0.05). CONCLUSION: There is a high expression of Sema4C in esophageal cancer, gastric cancer and rectal cancer. And it is strongly correlated with lymphatic metastasis. Thus Sema4C may play critical roles in the invasion and lymphatic metastasis of esophageal cancer, gastric cancer and rectal cancer.


Assuntos
Neoplasias Esofágicas/metabolismo , Neoplasias Retais/metabolismo , Semaforinas/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Mucosa/patologia , Metástase Neoplásica , Neoplasias Retais/patologia , Neoplasias Gástricas/patologia
17.
Zhonghua Yi Xue Za Zhi ; 92(23): 1641-5, 2012 Jun 19.
Artigo em Chinês | MEDLINE | ID: mdl-22944136

RESUMO

OBJECTIVE: To screen and prepare the vaccine of human papillomavirus (HPV) 18 E7 peptide target at human leukocyte antigen (HLA)-A2 plus CpG through SYFPEITHI. METHODS: (1) The SYFPEITHI database was employed for predicting and screening of HPV18 E7 HLA-A2 restricted T cell epitopes.(2) The peripheral blood and tumor tissue sample of HLA-A2 positive and HPV18 positive/negative patients were collected and randomly divided into 7 groups, i.e. E7PA + CpG, E7PB + CpG, E7PC + CpG, E7PD + CpG, CpG, IR-T + CpG and control groups respectively. T cell proliferation was detected by thiazolyl blue tetrazolium bromide (MTT) assay at different timepoints. Lactate dehydrogenase delivery method (LDH) was used to test the cytolytic t lymphocyte (CTL) activity of peripheral blood mononuclear cell (PBMC) in different ratios of effect and target (E:T). And the level of activity T cells was evaluated by interferon gamma (IFN-γ)-related enzyme-linked immuno-spot assay (ELISPOT). RESULTS: (1) Four peptides named E7PA, E7PB, E7PC and E7PD were obtained separately with high levels of affinity and specificity. (2) During continuous observations after vaccination, the E7PA + CpG group had the most pronounced proliferation rate. When E:T = 100:1, the E7PA + CpG group had more powerful CTL effect than the control group with statistic significance (P < 0.00). E:T was concentration-dependent. Except for IR-T + CpG, all other groups had great difference than control group with statistic significance (P < 0.05) but no significant difference between the groups. The levels of IFN-γ spot-forming T cells were higher in the E7PA + CpG group than the control group with statistic significance (P < 0.01). In terms of specificity, E7PA + CpG in the HPV18 positive group could induce the proliferation of IFN-γ-secreting T cells. And there was statistical difference with the control group (P < 0.05). CONCLUSION: Screening the HPV18 E7 peptide target at HLA-A2 plus CpG as the candidate targets by SYFPEITHI may active specific immunological cellular responses to HPV18 positive disease.


Assuntos
Ilhas de CpG , Proteínas de Ligação a DNA/imunologia , Proteínas Oncogênicas Virais/imunologia , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Peptídeos/imunologia , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/virologia
18.
Zhonghua Fu Chan Ke Za Zhi ; 45(6): 445-8, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21029596

RESUMO

OBJECTIVE: To explore the sensitivity and the molecular mechanism of cisplatin-resistance ovarian cancer cell line C13 to proteasome inhibitors and the combination with cisplatin. METHODS: After different treatments, methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, annexin-V/propidium iodide (PI) apoptosis detection kit was used to determine the apoptosis rate of different groups, western blot assay was introduced to evaluate the expression levels of Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIPs), and the activity of caspase-8 was examined. RESULTS: MTT assay shown that the cell viability ratios of combination group at serial time points from 12, 24, 36, 48, 60, 72 hours were (56.0 ± 8.4) %, (44.7 ± 7.3) %, (33.7 ± 11.2) %, (27.6 ± 8.0) %, (27.6 ± 7.6) % and (28.1 ± 2.4) %, which were much lower than those of cisplatin group (P < 0.05). After treated for 24 hours, apoptosis rates of cisplatin group, bortezomib group and combination group were (16.7 ± 1.7) %, (23.4 ± 2.1) % and (26.9 ± 1.6) %, respectively. The rate of combination group was much higher than that of non-treated group and that of cisplatin group or bortezomib group (P < 0.05). Western blot assay showed the changes of expression levels of cFLIPs, which were down-regulated seriously after cisplatin, bortezomib or combination treatment [(43.2 ± 2.3) % vs (75.7 ± 3.0) % vs (67.9 ± 2.1) %, P < 0.05]. The caspase-8 activity of combination group was (5.6 ± 1.6) folds than that of non-treated group, which was higher than those of other two groups [(2.3 ± 1.0) and (4.2 ± 0.9) folds, P < 0.05]. CONCLUSIONS: The tumor cell lethal effect of cisplatin could be increase significantly by the combination application of proteasome inhibitors, bortezomib. And the cFLIPs/caspase-8 signaling pathway may be play an important role in the molecular mechanism of the combination treatment.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Ovarianas/patologia , Inibidores de Proteases/farmacologia , Antineoplásicos/administração & dosagem , Western Blotting , Ácidos Borônicos/administração & dosagem , Bortezomib , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Inibidores de Proteases/administração & dosagem , Pirazinas/administração & dosagem
19.
Zhonghua Yi Xue Za Zhi ; 90(43): 3035-9, 2010 Nov 23.
Artigo em Chinês | MEDLINE | ID: mdl-21211321

RESUMO

OBJECTIVE: to the explore the effect of Human papillomavirus (HPV) 16 peptide vaccine in combination with paclitaxel-cisplatin (TP) chemotherapy on cervical cancer in vitro and in vivo. METHODS: (1) the major histocompatibility complex (MHC) class I restricted T cell epitopes were studied by bioinformatics for transporter associated with antigen processing (TAP). Their effects were compared and E7Pa had the most dramatic effect. (2) In vivo, the C57BL/6 mice were divided equally into 6 groups randomly after loading with TC-1 cells (HPV 16 positive tumor cells from C57BL/6 mouse), named as E7Pa + CpG + TP, E7Pa + CpG, CpG + TP, TP and CpG group as experiment groups and control (blank injection with physiological saline). The tumor volumes were measured regularly by tumor growth curve to compare the therapeutic effects in different groups; the related cell factors in murine peripheral blood were evaluated by enzyme-linked immunosorbent assay (ELISA); the TUNEL test kit was used to explore cellular apoptosis in tumor tissue; the survival curve was drawn from the TC-1 cell loading to natural death; safety was tested by pathological test and leucocyte count. RESULTS: at day 60 of tumor growth, the tumor volume of immunotherapy plus TP chemotherapy group was (0.013 ± 0.010) cm(3) versus the control (1.900 ± 0.075) cm(3) with a great significant deviation (P < 0.01). Meanwhile, the volumes were E7Pa + CpG group (0.340 ± 0.038) cm(3), TP + CpG group (0.650 ± 0.029) cm(3), TP group (1.100 ± 0.052) cm(3) and that of CpG group was (0.890 ± 0.047) cm(3) separately. And these groups had significant difference with the controls (P < 0.05). The average survival time of different groups were E7Pa + CpG + TP group (108.50 ± 8.97) d, E7Pa + CpG group (100.02 ± 2.27) d, CpG + TP group (79.63 ± 4.05) d, TP group (73.24 ± 3.11) d, CpG group (68.63 ± 1.38) d and controls (52.37 ± 2.47) d. And the difference between the E7Pa + CpG + TP and E7Pa + CpG groups had great significance with the controls (P < 0.01). Furthermore, the immune system was effectively stimulated for suppressing tumor growth in the immunotherapy group while cell apoptosis was significantly induced in the chemotherapy group. The combination of immunotherapy and chemotherapy was significantly efficacious than either of them alone. And it could thoroughly stimulate the immune effects and enhance the anti-tumor function of chemotherapeutical drugs. In safety test, there was no significant difference among all groups. CONCLUSION: the HPV16 peptide vaccine in combination with TP chemotherapy can treat the HPV16 E7 positive tumor effectively in experiment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Papillomavirus Humano 16/imunologia , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/terapia , Animais , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia
20.
Zhonghua Fu Chan Ke Za Zhi ; 44(12): 903-8, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20193416

RESUMO

OBJECTIVE: To prepare the human papillomavirus (HPV) 16 peptide vaccine and explore the effect in vitro and in vivo. METHODS: (1) Prediction of the major histocompatibility complex (MHC) class I restricted T cell epitopes by bioinformatics target at transporter associated with antigen processing (TAP) and named by E7Pa, E7Pb, E7Pc separately. (2) In vivo, the C57BL/6 mice were divided into five groups with same amounts randomly after loading with TC-1 cells (HPV 16 positive tumor cells from C57BL/6 mouse), named as E7Pa + CpG, E7Pb + CpG, E7Pc + CpG (as experiment groups, and added 50 microg/ml E7Pa, E7Pb, E7Pc, respectively), CpG (as positive control group and added Con A with 12 mg/L final concentration) and blank control group (without any treatment). The T cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay at different time points; the lactate dehydrogenase (LDH) delivery method was used to test the cytolytic T lymphocyte (CTL) activity of mouse splenic lymphocyte in different ratio of effector cells and target cells (E:T); the related cytokines in tumor tissue and mouse peripheral blood were evaluated by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The tumor volumes were measured to contrast the therapeutic effect in different groups. RESULTS: (1) Three peptide named E7Pa, E7Pb, E7Pc were successfully preparated which had high affinity and specificity. (2) After vaccination of 24, 48, 72, 96 hours, MTT results shown that the proliferation rate in E7Pa + CpG group were (131 +/- 32)%, (302 +/- 15)%, (552 +/- 28)%, (731 +/- 24)% individually, which were much higher than those in blank control [(72 +/- 15)%, (120 +/- 57)%, (176 +/- 41)%, (288 +/- 29)%; P < 0.01], and the other groups i.e. E7Pb + CpG, E7Pc + CpG and CpG groups all proliferated much higher than those in blank control group with statistic signification (P < 0.05), but there was no significant difference between groups (P > 0.05); the LDH delivery assay showed that when the ratio of E:T was 100:1, the activity of CTL in the E7Pa + CpG group was most powerful than the other groups with statistic signification (P < 0.01).Meanwhile, the ratio of E:T was concentration-dependent. Compared E7Pb + CpG, E7Pc + CpG or CpG groups with blank control group, there were significantly difference (P < 0.05), while there was no significant difference between groups (P > 0.05). The mRNA levels of interferon gamma (IFN-gamma), interleukin-2 (IL-2) in tumor tissue and peripheral blood in E7Pa + CpG group were significantly higher than those in blank control group (P < 0.01), which was the similar results when compared E7Pb + CpG, E7Pc + CpG or CpG groups with control group (P < 0.05), and without significant difference between groups (P > 0.05). The tumor volumes were suppressed obviously in all the experiment groups, especially at the 60th days, the volumes in E7Pa + CpG group were much smaller than that in blank control group with statistic signification (P < 0.01), which was the similar results that E7Pb + CpG, E7Pc + CpG or CpG groups had difference than blank control group with statistic signification (P < 0.05), and without significant difference between groups (P > 0.05). CONCLUSION: The HPV16 E7 peptide target at TAP combination with CpG as a vaccine could treat effectively the HPV16 E7 positive tumor in experiment.


Assuntos
Papillomavirus Humano 16 , Interleucina-2 , Animais , Humanos , Interferon gama , Camundongos Endogâmicos C57BL , Vacinas de Subunidades Antigênicas
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