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OBJECTIVE: To study the illness cognition and related factors in patients with prostate cancer (PCa). METHODS: Using the convenience-sampling method, we selected 231 PCa patients treated in a general hospital in Xuzhou from October 2019 to October 2020. We conducted a cross-sectional study of the cases based on the general data of the patients and their scores on the Illness Cognition Questionnaire (ICQ). RESULTS: The PCa patients showed a high negative and a low positive illness cognition. The ICQ scores of the patients were high on "helplessness" (13.70 ± 3.54) and low on "acceptance" (16.64 ± 3.37) and "perceived benefits" (13.93 ± 3.76). Age, disease duration, disease stage and number of children were the four factors included in the regression equation of the participants' illness cognition. CONCLUSION: Negative illness cognition is high in PCa patients, higher in those at a younger age, with a longer disease duration, or with more than one child than in those at an older age, with a shorter disease duration, or with only one or no child.
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Cognição , Neoplasias da Próstata , Masculino , Humanos , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To explore the role of community-based reproductive health service in improving male reproductive health-related knowledge, behavior and psychology in middle-aged and elderly men. METHODS: We recruited 136 men aged 40ï¼69 years from 5 community health service centers in Xuzhou for this self-control study from July to August 2019. We carried out a 4-item health education among the subjects concerning reproductive health knowledge, reproductive system diseases, healthy life, and enjoying health. Before and at 6 months after education, we evaluated the effects of intervention using the General Condition Questionnaire, Reproductive System Symptoms Questionnaire, Male Reproductive Health-Related Knowledge, Attitude and Behavior Questionnaire, and the Chinese version of Connor-Davidson Resilience Scale. RESULTS: At 6 months after intervention, the subjects showed significantly increased scores on healthy eating habits, male reproductive health cognation and psychological resilience, and decreased unhealthy behaviors and positive rate of reproductive system symptoms as compared with those before intervention (all P < 0.05). The cost-effectiveness ratio of the study was 7.75. CONCLUSIONS: Community-based reproductive health service can effectively improve the reproductive health-related knowledge and psychology, eating habits and healthy behaviors of middle-aged and elderly men. And it has a high cost-effectiveness ratio and is worthy of promotion in other communities.
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Serviços de Saúde Comunitária , Serviços de Saúde Reprodutiva , Idoso , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Reprodutiva , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To explore the effect of family-centered psychological support (FCPS) on illness cognition and quality of life in patients with advanced prostate cancer (PCa). METHODS: Using a randomized controlled study design, we divided 84 advanced PCa patients into an intervention group and a control group, all provided with PCa-related knowledge and answers to their questions, while the former group with FCPS in addition. Before, immediately after and at 1 and 3 months after intervention, we evaluated the effectiveness using the Illness Cognition Questionnaire (ICQ) and Functional Assessment of Cancer Therapy ï¼ Prostate (FACT-P). RESULTS: Totally, 78 of the patients completed the whole intervention procedure, 38 in the intervention and 40 in the control group. There were statistically significant differences between the intervention and control groups in the scores on the three factors of ICQ acceptance (17.89 ± 3.86 vs 15.20 ± 2.83, t = 3.528, P < 0.05), perceived benefits (18.68 ± 3.02 vs 17.08 ± 2.74, t = 2.465, P < 0.05) and helplessness (13.37 ± 3.00 vs 15.63 ± 3.11, t = ï¼3.259, P < 0.05) immediately after intervention, and so were there at 1 and 3 months after intervention (P < 0.05). The patients in the intervention group showed remarkably higher quality of life scores than the controls immediately after (100.59 ± 11.66 vs 92.20 ± 9.54, t = 7.943, P < 0.05) and at 1 month (93.03 ± 13.33 vs83.55 ± 14.29, t = 3.481, P < 0.05) and 3 months after intervention (85.66 ± 17.39 vs 75.95 ± 16.66, t = 3.025, P < 0.05). The covariance analysis found that, excluding the time effect, FCPS significantly improved the positive illness cognition of the patients (P < 0.05). CONCLUSIONS: Family-centered psychological support contributes to the positive illness cognition of the patients with advanced PCa and helps improve their quality of life, and therefore deserves to be popularized in clinical practice.
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Cognição , Aconselhamento , Neoplasias da Próstata , Qualidade de Vida , Família , Humanos , Masculino , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/terapiaRESUMO
Recent studies suggest that SATB1 is a promising therapeutic target for prostate cancer. To develop novel SATB1-based therapeutic agents for prostate cancer, in this study, we aimed to construct ZD55-SATB1, an oncolytic adenovirus ZD55 carrying shRNA targeting SATB1, and investigate its effects on the inhibition of prostate cancer growth and metastasis. ZD55-SATB1 was constructed and used to infect human prostate cancer cell lines DU145 and LNCaP. The inhibitory effect of ZD55-SATB1 on SATB1 expression was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The cytotoxicity of ZD55-SATB1 was detected by MTT assay. Cell invasion was detected by Matrigel invasion assay. The in vivo antitumor activities of ZD55-SATB1 were evaluated in xenograft mouse model. We found that ZD55-SATB1 selectively replicated and significantly reduced SATB1 expression in DU145 and LNCaP cells. ZD55-SATB1 effectively inhibited the viability and invasion of DU145 and LNCaP cells in vitro and inhibited prostate cancer growth and metastasis in xenograft nude mice. In conclusion, replicative oncolytic adenovirus armed with SATB1 shRNA exhibits effective antitumor effect in human prostate cancer. Our study provides the basis for the development of ZD55-SATB1 for the treatment of prostate cancer.
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Proliferação de Células/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/antagonistas & inibidores , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , Camundongos , Vírus Oncolíticos/genética , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate whether chlorophyllin could protect human umbilical vein endothelial cell (HUVEC) against oxidative damage by inducing the expression of heme oxygenase-1 (HO-1) and to explore the underlying mechanism. METHODS: The cellular protection of chlorophyllin against oxidative damage was detected by cell-survival assay with flow cytometry. The level of free radicals was detected directly by electron spin resonance spectra. The induced expression of HO-1 was shown by RT-PCR, Western blot, immunofluorescence confocal laser microscopy and enzymatic activity test. Whether the activation of PI3K/Akt pathway was involved was detected by Western blot. RESULTS: Chlorophyllin could protect HUVEC against oxidative damage caused by H2O2 via scavenging the excessive free radicals. Chlorophyllin treatment could induce expression of HO-1 in a dose- and time-dependent manner. The activation of PI3K/Akt pathway was required in the induction of HO-1. LY294002, the specific inhibitor of PI3K, could suppress the activation of PI3K/Akt and the induced expression of HO-1 in a dose-dependent manner. CONCLUSIONS: Chlorophyllin shows cellular protection against oxidative damage by counteracting the excessive free radicals. Up-regulation of HO-1 expression plays a pivotal role in the protection of chlorophyllin, while the activation of PI3K/Akt signaling pathway is required in the induction of HO-1.
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Clorofilídeos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas , Cromonas/farmacologia , Heme Oxigenase-1 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Prostate cancer (PCa) is a common malignant tumor of the male urinary system and ranks the second in the causes of tumor-related deaths. Differential display code 3 (DD3) is a noncoding gene that is specifically expressed in PCa. High expression of sperm-associated antigen 9 (SPAG9) is closely related to tumorigenesis of PCa, and SPAG9 is a therapeutic target for PCa. In this study, a new oncolytic adenovirus DD3-ZD55-SPAG9 was constructed by using DD3 promoter to enhance the efficacy and safety of adenovirus. The combined use of DD3-ZD55-SPAG9 and docetaxel showed that DD3-ZD55-SPAG9 significantly improved the anti-tumor efficacy of docetaxel in PCa both in vitro and in vivo. The mechanism was related to the induction of tumor cell apoptosis and the inhibition of tumor cell invasion. In conclusion, DD3-ZD55-SPAG9 combined with docetaxel is an effective strategy for PCa therapy.
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Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity. Recent efforts have been focused on the modification of oncolytic adenovirus by encoding transgenes within the viral genome to efficiently and selectively replicate within cancer cells, destroy cancerous cells, induce tumor cell apoptosis, and stimulate the recruitment of immune cells to the tumor site. Nevertheless, there are still big challenges for translational research of oncolytic virotherapy in clinical cancer management. Therefore, here we summarize current status on the design and application of oncolytic adenovirus vectors for prostate cancer therapy. In particular, we describe the main receptors associated with the tropism and transduction of oncolytic adenovirus vectors, and propose new directions in future studies for prostate cancer virotherapy.
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Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias da Próstata , Adenoviridae/genética , Linhagem Celular Tumoral , Vetores Genéticos/genética , Humanos , Masculino , Vírus Oncolíticos/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , TropismoRESUMO
OBJECTIVE: To construct an oncolytic adenovirus with the DD3 promoter regulation, expressing small hairpin RNA and targeting the SATB1 gene (SATBI-shRNA), and to evaluate its potential for inhibiting the growth of human prostatic carcinoma cells (LNCaP) in vitro. METHODS: SATB1-shRNA expression cassettes containing the H1 promoter were produced by PCR from pSilencer3. 1-SATB1 and inserted into the pZD55 vector, and the recombinant plasmid pZD55-SATB1-shRNA was constructed, pZD55SATB1-shRNA and pZXC2-DD3-E1A were digested with EcoRV and Xba I , and the obtained expression cassettes linked each other to construct the recombinant plasmid pDD3-ZD55-SATB1, which was cotransfected with the pBHGE3 packaging plasmids mixture into 293 cells by Effectence. The recombined adenoviruses DD3-ZD55-SATB1 were identified by PCR. Viruses were propagated on HEK293 cells and purified by standard techniques, and the functional PFU titers determined by plaque assay on 293 cells. The antitumor potential of DD3-ZD55-SATB1 to LNCaP was evaluated by the crystal violet dye method. The expression level of the E1A gene was detected by Western blot, and that of the SATB1 gene in the adenovirus-infected LNCaP cells by both Western blot and RT-PCR. RESULTS: An oncolytic adenovirus expressing SATB1-shRNA with the DD3 promoter regulation, DD3-ZD55-SATB1, was constructed successfully, whose functional PFU titer was 1.2 x 10(10) PFU/ml. DD3-ZD55-SATB1 showed an obvious cytopathic effect and a selective expression of E1A in the adenovirus-infected LNCaP cells; it exhibited a high LNCaP-targetability and specific SATB1-silencing effect. CONCLUSION: The successful construction of the oncolytic adenovirus DD3-ZD55-SATB1 offers a new tool for researches on the gene therapy for human prostate cancer.
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Adenoviridae/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Vírus Oncolíticos/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Carcinoma/terapia , Linhagem Celular Tumoral , Vetores Genéticos , Humanos , Masculino , Terapia Viral Oncolítica/métodos , Regiões Promotoras Genéticas , Neoplasias da Próstata/terapiaRESUMO
Prostate cancer is a common malignant tumor and the second leading cause of cancer-related death in men. Radiation therapy is a curative treatment for localized prostate cancer and has a limited effect for castration-resistant prostate cancer (CRPC). Interleukin 24 (IL-24) has a radiosensitizing effect in cancer cells. Our previous studies showed that ZD55-IL-24, an oncolytic adenovirus harboring IL-24, had better anti-tumor effect with no toxicity to normal cells. In this study, we evaluated the synergistic anti-tumor effect of oncolytic adenovirus ZD55-IL-24 combined with radiotherapy in prostate cancer. In Vitro and In Vivo experiments showed that the combined therapy significantly inhibited the growth of prostate cancer and provoked apoptosis of prostate cancer cells. In conclusion, the combination of ionizing radiation and oncolytic adenovirus expressing IL24 could achieve synergistic anti-tumor effect on prostate cancer, and is a promising strategy for prostate cancer therapy.
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OBJECTIVE: To improve the diagnosis and treatment of far advanced prostate cancer without clinically detectable bone metastasis. METHODS: Cancer metastatic lesions were found in the liver and lungs respectively of two patients on routine medical examination, and only an abnormally elevated level of the serum prostate specific antigen (PSA) was observed in the following system examinations. The patients were diagnosed as having prostate cancer by prostate biopsy. MRI showed a discontinued prostate capsule, and ECT revealed no bone metastasis. Diagnostic treatment was conducted by giving LHRHa combined with antiandrogens. One of the patients underwent surgical castration at 12 months, and both received intensity modulated radiation therapy (80 Gy) at 15 and 18 months, respectively. RESULTS: The metastatic lesions in the liver and lungs of the patients were either absent or significantly reduced after treated by maximal androgen blockade for 3 months, and all disappeared after 6 months'treatment, with the PSA level stabilized at less than 0.02 microg/L in one patient, and around 0.5 microg/L in the other. Antiandrogen treatment was suspended after radiotherapy. The results of liver, lung and bone scanning were normal during the 12-month follow-up, and the PSA level was below 1.0 microg/L. CONCLUSION: Remote metastasis of prostate cancer may occur in ectosteal organs first, which deserves special attention. A combination of different treatment methods promises satisfactory results.
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Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapiaRESUMO
PURPOSE: Oncolytic adenoviruses emerge as new agents for cancer therapy. This study aimed to investigate the synergistic anti-tumor activity of oncolytic adenovirus armed with IL-24 (ZD55-IL-24) and docetaxel (DTX) on advanced prostate cancer in vitro and in vivo. METHODS: DU145 prostate cancer cells or nude mice xenografted with DU145 prostate cancer cells were treated by ZD55-IL-24 and DTX alone or in combination. RESULTS: DTX did not affect ZD55-IL-24 replication and IL-24 expression in DU145 cells. In vitro, the combination of ZD55-IL-24 and DTX showed synergistic inhibitory effects on prostate cancer cell viability and invasion. In vivo, ZD55-IL-24 and DTX synergistically inhibited the growth and activated the apoptosis of DU145 xenografts, accompanied by significantly decreased PARP-1 levels and increased caspase-3 and caspase-8 levels as well as decreased CD31 expression. CONCLUSION: We reported the synergistic anti-tumor efficacy of ZD55-IL-24 and DTX on prostate cancer. Our results suggest that chemotherapy combined with oncolytic adenovirus mediated gene therapy is a promising strategy for the treatment of advanced prostate cancer.
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BACKGROUND: Post-stroke depression (PSD) is the most common psychiatric complication after a stroke. The most frequently used antidepressants are selective serotonin receptor inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), however, these exhibit a series of side effects. Traditional Chinese medicine has been used to treat PSD with few side effects. The aim of this study is to evaluate the efficacy and safety of Jiedu Tongluo granules for treating PSD with qi deficiency and blood stasis syndrome. METHODS: The planned study is a double-blind, randomized, placebo-controlled pilot trial. Eighty participants will be randomly assigned to receive either treatment or placebo. The treatment group will receive Jiedu Tongluo granules (JDTLG) with conventional treatment, and the placebo group will receive placebo with conventional treatment for 8 weeks. The primary outcome is the effectiveness of JDTLG on depression after 8 weeks treatment, which is defined as a decrease of 50% or more in 17-item Hamilton Depression Scale (HAMD-17) score or clinical recovery (score < 7). Secondary outcomes are improvement in neurological function, degree of independence, activities of daily living, and TCM syndrome at each visit, which will be measured with National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and TCM scale, respectively. Interleukin (IL)-6, IL-8, and small-molecule metabolites will be monitored to explore the mechanism of action of JDTLG on PSD. Safety measures include vital signs, results of electrocardiography, laboratory index (full blood count, kidney and liver function tests) and adverse events. DISCUSSION: The purpose of this trial is to evaluate the therapeutic effects and safety of JDTLG in individuals with PSD with concomitant qi deficiency and blood stasis syndrome. If successful, the outcome of this trial will provide a viable treatment option for PSD patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03147053 . Registered on 27 April 2017.
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Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/psicologia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Adesão à Medicação , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos PilotoRESUMO
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins. In addition, prostate cancer cells modulate surrounding stromal cells via the exosomes. Affected stromal cells employ the exosomes to modulate microenvironment and promote tumor growth and metastasis. Exosomes derived from prostate cancer cells contribute to cancer chemoresistance. The lipid bilayer membrane of the exosomes makes them promising carriers of drugs and other therapeutic molecules targeting prostate cancer. Furthermore, exosomes can be detected and isolated from various body fluids for the diagnosis of prostate cancer.
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Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy.
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Adenoviridae , Antineoplásicos/farmacologia , Dacarbazina/farmacologia , Interleucina-18/farmacologia , Melanoma/terapia , Adenoviridae/fisiologia , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dacarbazina/uso terapêutico , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Interleucina-18/uso terapêutico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Melanoma/patologia , Camundongos , Camundongos Nus , Terapia Viral Oncolítica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Special AT-rich sequence binding protein 1 (SATB1) plays important role in the regulation of chromatin structure and gene expression. Recent studies have indicated oncogenic role of SATB1. However, the function of SATB1 in prostate cancer progression and metastasis remains unclear. In this study SATB1 expression vector or siRNA was employed to modulate the expression level of SATB1 in prostate cancer cells and xenograft tumor in nude mouse model. Immunohistochemical analysis was performed on clinical prostate cancer samples. Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous tumor in nude mice. Immunohistochemical and Western blot analysis of the xenografts showed that silencing SATB1 led to decreased expression of vimentin and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led to increased expression of vimentin and MMP2 and decreased expression of E-cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased significantly while E-cadherin expression was reduced significantly in clinical samples of prostate carcinoma with metastasis compared to prostate carcinoma without metastasis and benign prostate hyperplasia. Taken together, these findings suggest that the modulation of epithelial-mesenchymal transition by SATB1 may contribute to prostate cancer metastasis.
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Transição Epitelial-Mesenquimal , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Antígenos CD , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Neoplasias da Próstata/genética , Tela Subcutânea/patologia , Vimentina/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To observe the changes in peripheral blood T lymphocyte rDNA transcription activity and to study the significance of immune monitoring for patients with chronic benzene poisoning. METHODS: Venous blood samples were withdrawn from 39 patients with chronic benzene poisoning, 20 patients with malignant disease and 22 healthy controls. Cell culture, argyrophil staining method, I-CLQ cell image analysis system were used in this study. rDNA transcription activity which was expressed by the ratio of integrated area (IA) of nucleolus to that of nucleus, and the ratio of integrated optical density (IOD) of argyrophilic nucleolus to that of argyrophilic nucleus. RESULTS: (1) The value of IA and IOD in chronic benzene poisoning patients (7.95% +/- 1.13% and 7.15% +/- 1.15% respectively) were lower than those in controls (9.59% +/- 1.26% and 8.92% +/- 1.18% respectively), P < 0.01. The value of IA and IOD in chronic moderate benzene poisoning patients (6.54% +/- 0.88%) and (5.47% +/- 0.80%) were lower than those to be observed (7.98% +/- 1.06% and 7.13% +/- 0.96% respectively) as well as in mild poisoning patients (8.19% +/- 1.06% and 7.44% +/- 1.06% respectively), P < 0.05. (2) The value of IA and IOD in malignant group (4.10% +/- 1.50%, 3.67% +/- 1.42%) were much more lower than those in controls and in chronic benzene poisoning patients (P < 0.01). CONCLUSION: rDNA transcription activity may be an index to monitor the cellular immune function of chronic benzene poisoning patients.
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Benzeno/intoxicação , DNA Ribossômico/genética , Linfócitos T/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismoRESUMO
OBJECTIVES: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. METHODS: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. RESULTS: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AAµAC genotype (P<0.05). CONCLUSION: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células de Transição/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Proteínas Nucleares/genética , Polimorfismo Genético/genética , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária/metabolismo , Povo Asiático/genética , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Ilhas de CpG/genética , Metilação de DNA , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Fatores de Risco , Neoplasias da Bexiga Urinária/patologiaRESUMO
Malignant melanoma is one of the most lethal and aggressive human malignancies. It is notoriously resistant to all of the current therapeutic modalities, including chemotherapy. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to the malignancy of melanoma. Dacarbazine (DTIC) has been considered as the gold standard for melanoma treatment with a response rate of 15-20%. Unfortunately, the resistance to this chemotherapeutic agent occurs frequently. ZD55-IL-24 is a selective conditionally replicating adenovirus that can mediate the expression of interleukin-24 (IL-24) gene, which has a strong anti-tumor effect. In this study, we hypothesized that a combination of ZD55-IL-24-mediated gene virotherapy and chemotherapy using DTIC would produce an increased cytotoxicity against human melanoma cells in comparison with these agents alone. Our results showed that the combination of ZD55-IL-24 and DTIC significantly enhanced the anti-tumor activity by more effectively inducing apoptosis in melanoma cells than either agent used alone without any overlapping toxicity against normal cells. This additive or synergistic effect of ZD55-IL-24 in combination with DTIC in killing human malignant melanoma cells implies a promising novel approach for melanoma therapy.
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Adenoviridae/fisiologia , Antineoplásicos/farmacologia , Dacarbazina/farmacologia , Terapia Genética/métodos , Interleucinas/genética , Melanoma/terapia , Terapia Viral Oncolítica/métodos , Adenoviridae/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Terapia Combinada , Regulação para Baixo , Humanos , Interleucinas/biossíntese , Melanoma/genética , Melanoma/metabolismo , Melanoma/virologia , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/fisiologia , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução Genética , Regulação para Cima , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética , Proteína bcl-X/biossíntese , Proteína bcl-X/genéticaRESUMO
It has been demonstrated that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. ZD55-IL-18 could express substantially more IL-18 than Ad-IL-18 because of replication of the vector. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in renal cell carcinoma. ZD55-IL-18 significantly decreased VEGF and CD34 expression in the tumor cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity via inhibition of angiogenesis and offer a novel approach to cancer therapy.