A mathematical modeling of tumor therapy with oncolytic viruses is discussed. The model consists of two coupled, deterministic differential equations allowing for cell reproduction and death, and cell infection. The m...A mathematical modeling of tumor therapy with oncolytic viruses is discussed. The model consists of two coupled, deterministic differential equations allowing for cell reproduction and death, and cell infection. The model is one of the conceptual mathematical models of tumor growth that treat a tumor as a dynamic society of interacting cells. In this paper, we obtain an approximate analytical expression of uninfected and infected cell population by solving the non-linear equations using Homotopy analysis method (HAM). Furthermore, the results are compared with the numerical simulation of the problem using Matlab program. The obtained results are valid for the whole solution domain.展开更多
Among 6706 women screened by cytology, only 9 (0.13%) showed evidence of human pppillomavirus infection (HPVI). In 133 women examined by colposcopy for abnormal cytology or/ and suspected lestions on the cervix, 41.(3...Among 6706 women screened by cytology, only 9 (0.13%) showed evidence of human pppillomavirus infection (HPVI). In 133 women examined by colposcopy for abnormal cytology or/ and suspected lestions on the cervix, 41.(30. 8%) showed subclinical papillomavirus infection (SPI), while 17. 4% and 5. 3% showed HPVI by histopathology and cytology, respectively. The conformation rate between colposcopy and pathology was 69. 6%. Sixty-nine specimens out of 133 colposcopy piled biopaies were assayed by HPV-DNA dot hybridization with 6B/11, 16, 18 probes to detect the presence of HPV-DNA In the cervical specimens. Thirty-nine (56.5%) gave a positive result. The colposcopic predictive value of positive result for HPVI was 76.7%. The difference between colposcopy (59%) and pathology (20. 5%) is statistically significant (P<0. 01). These results suggest that colposcopy is superior to cytology and hjstopathology for the detection of SPI in the cervix. In colposcopy HPV-DNA positive women, aceto while epithelium was most common (28. 2%) . As it is difficult to differentiate SPI from cervical intraepithelial neoplasia especially the Grade Ⅰ lesion by colposcopy, discrimination criteria are proposed together with the chief colposcopic features of SPI.展开更多
The antiretroviral action of dC14 in vitro has been proven in previous experiments. This paper deals with the effect of dC14 in vivo.Intraperitoneal inoculation of tumor cells into mice without dC14 treatment induced ...The antiretroviral action of dC14 in vitro has been proven in previous experiments. This paper deals with the effect of dC14 in vivo.Intraperitoneal inoculation of tumor cells into mice without dC14 treatment induced ascitic tumors after a latency of 6 days and death of the mice after 11 days. Both incidence and mortality of disease were 100%. In animals receiving dC14 treatment, the incidence and mortality were less, latency and survival periods were longer. Viral sequences could be detected in tumor cells and in spleens of tumor cell inoculated animals, receiving dC14 treatment or not but could not be detected in normal animals. Studied suggest that the suppressive action of dC14 on the development of mouse SRS ascitic tumor may be through blocking gene expression of virus.展开更多
Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonala...Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.展开更多
AIM To study hepatocarcinogenesis of hepatitis C virus (HCV). METHODS Expression of HCV antigens (CP10, NS3 and NS5) and several cancer associated gene products (ras p21, c myc, c erbB 2, mutated p53 and p16 pr...AIM To study hepatocarcinogenesis of hepatitis C virus (HCV). METHODS Expression of HCV antigens (CP10, NS3 and NS5) and several cancer associated gene products (ras p21, c myc, c erbB 2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n =46) and its surrounding liver tissue were studied by the ABC (avidin biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group. RESULTS Positive immunostaining with one, two or three HCV antigens was found in 20 (43 5%) cases, with either of two or three HCV antigens in 16 (34 8%) cases, and with three HCV antigens in 9 (19 6%) cases. Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20) was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups. CONCLUSION HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibiting the function of p16 gene, which acts as a negative regulator of cell cycle.展开更多
The resurgence of infectious diseases on the African continent plays a major role in the increase in cancer occurrence. Whereas in developed countries the causes of occurrence of cancers are related mainly to non-infe...The resurgence of infectious diseases on the African continent plays a major role in the increase in cancer occurrence. Whereas in developed countries the causes of occurrence of cancers are related mainly to non-infectious factors;cancers of infectious origin become a dramatic particularity in Africa. The proportion of virus-induced cancers may reach up to 75% of cancer cases in certain countries. Oncogenic viruses such as human papilloma virus (HPV), hepatitis viruses B and C, human herpes virus 8 and Epstein Barr virus in association with human immunodeficiency virus are the main viral etiologies of cancers in Africa, representing around 30% of cancers causes. Optimistically, 30% of cancers could be prevented in Africa. However, health burden prevails on the continent due to the weakness of health policy especially regarding preventive medicine, but also the limited technical facilities, poor manpower and insufficient political commitment. We felt urgent to review the state of the art of the question, and necessary to analyze and publicize the current epidemiological advances in oncogenic viruses and virus-induced cancers in Africa. Prevention implies understanding, which is compulsory to reverse the current trends and to potentially instate a control of virus-induced cancers.展开更多
Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct che...Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.展开更多
目前国内外对肾上腺皮质激素治疗重型肝炎的利弊存在一定的争议.但 Muto et al 报告,1993年从日本各大中心收集的数百例暴发性病毒性肝炎(相当于我国的急性重型肝炎),用激素疗法者占52.7%～61.2%.我们应用激素短程疗法治疗病毒性重型肝...目前国内外对肾上腺皮质激素治疗重型肝炎的利弊存在一定的争议.但 Muto et al 报告,1993年从日本各大中心收集的数百例暴发性病毒性肝炎(相当于我国的急性重型肝炎),用激素疗法者占52.7%～61.2%.我们应用激素短程疗法治疗病毒性重型肝炎亦取得了一定的疗效,为进一步探讨其疗效机制,我们于1998-03/1999-06,对13例激素治疗的病毒性重型肝炎患者血清 TNFα和 sIL-2R 水平进行了观察.展开更多
Background Dendritic cells (DCs) are the most powerful antigen-presenting cells to induce specific T-cell immunity, which plays an important role in the body’s anti-tumor responses. In this study, we assessed the fe...Background Dendritic cells (DCs) are the most powerful antigen-presenting cells to induce specific T-cell immunity, which plays an important role in the body’s anti-tumor responses. In this study, we assessed the feasibility and efficacy of inducing T-cell immunity against Epstein-Barr virus (EBV)-associated tumors in vivo using dendritic cells transfected with EBV latent membrane 2A (LMP2A) recombinant adenovirus.Methods Cytokine-activated bone marrow-derived DCs transfected with EBV LMP2A recombinant adenovirus were infused into BALB/c mice. Splenic cytotoxic T-cell responses were evaluated by cytotoxicity and interferon-γ production assays. in vivo immune protection was then assessed in the mice tumor models implanted with tumor cells expressing EBV LMP2A.Results DCs transfected with EBV LMP2A recombinant adenovirus could strongly induce EBV LMP2A-specific cytotoxic T-cell responses and upregulate interferon-γ production in vivo. Vaccination using these DCs led to prolongation of overall survival rates in the mice tumor models and retarded tumor growth. Conclusions The results suggest that DCs transfected with EBV LMP2A recombinant adenovirus can serve as a feasible and effective tool for eliciting LMP2A-specific cytotoxic T-cell responses against EBV LMP2A in vivo in the treatment of EBV-associated tumors.展开更多
文摘A mathematical modeling of tumor therapy with oncolytic viruses is discussed. The model consists of two coupled, deterministic differential equations allowing for cell reproduction and death, and cell infection. The model is one of the conceptual mathematical models of tumor growth that treat a tumor as a dynamic society of interacting cells. In this paper, we obtain an approximate analytical expression of uninfected and infected cell population by solving the non-linear equations using Homotopy analysis method (HAM). Furthermore, the results are compared with the numerical simulation of the problem using Matlab program. The obtained results are valid for the whole solution domain.
文摘Among 6706 women screened by cytology, only 9 (0.13%) showed evidence of human pppillomavirus infection (HPVI). In 133 women examined by colposcopy for abnormal cytology or/ and suspected lestions on the cervix, 41.(30. 8%) showed subclinical papillomavirus infection (SPI), while 17. 4% and 5. 3% showed HPVI by histopathology and cytology, respectively. The conformation rate between colposcopy and pathology was 69. 6%. Sixty-nine specimens out of 133 colposcopy piled biopaies were assayed by HPV-DNA dot hybridization with 6B/11, 16, 18 probes to detect the presence of HPV-DNA In the cervical specimens. Thirty-nine (56.5%) gave a positive result. The colposcopic predictive value of positive result for HPVI was 76.7%. The difference between colposcopy (59%) and pathology (20. 5%) is statistically significant (P<0. 01). These results suggest that colposcopy is superior to cytology and hjstopathology for the detection of SPI in the cervix. In colposcopy HPV-DNA positive women, aceto while epithelium was most common (28. 2%) . As it is difficult to differentiate SPI from cervical intraepithelial neoplasia especially the Grade Ⅰ lesion by colposcopy, discrimination criteria are proposed together with the chief colposcopic features of SPI.
文摘The antiretroviral action of dC14 in vitro has been proven in previous experiments. This paper deals with the effect of dC14 in vivo.Intraperitoneal inoculation of tumor cells into mice without dC14 treatment induced ascitic tumors after a latency of 6 days and death of the mice after 11 days. Both incidence and mortality of disease were 100%. In animals receiving dC14 treatment, the incidence and mortality were less, latency and survival periods were longer. Viral sequences could be detected in tumor cells and in spleens of tumor cell inoculated animals, receiving dC14 treatment or not but could not be detected in normal animals. Studied suggest that the suppressive action of dC14 on the development of mouse SRS ascitic tumor may be through blocking gene expression of virus.
文摘Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.
文摘AIM To study hepatocarcinogenesis of hepatitis C virus (HCV). METHODS Expression of HCV antigens (CP10, NS3 and NS5) and several cancer associated gene products (ras p21, c myc, c erbB 2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n =46) and its surrounding liver tissue were studied by the ABC (avidin biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group. RESULTS Positive immunostaining with one, two or three HCV antigens was found in 20 (43 5%) cases, with either of two or three HCV antigens in 16 (34 8%) cases, and with three HCV antigens in 9 (19 6%) cases. Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20) was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups. CONCLUSION HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibiting the function of p16 gene, which acts as a negative regulator of cell cycle.
文摘The resurgence of infectious diseases on the African continent plays a major role in the increase in cancer occurrence. Whereas in developed countries the causes of occurrence of cancers are related mainly to non-infectious factors;cancers of infectious origin become a dramatic particularity in Africa. The proportion of virus-induced cancers may reach up to 75% of cancer cases in certain countries. Oncogenic viruses such as human papilloma virus (HPV), hepatitis viruses B and C, human herpes virus 8 and Epstein Barr virus in association with human immunodeficiency virus are the main viral etiologies of cancers in Africa, representing around 30% of cancers causes. Optimistically, 30% of cancers could be prevented in Africa. However, health burden prevails on the continent due to the weakness of health policy especially regarding preventive medicine, but also the limited technical facilities, poor manpower and insufficient political commitment. We felt urgent to review the state of the art of the question, and necessary to analyze and publicize the current epidemiological advances in oncogenic viruses and virus-induced cancers in Africa. Prevention implies understanding, which is compulsory to reverse the current trends and to potentially instate a control of virus-induced cancers.
基金Supported by United States National Institutes of Health grant,No.R01AI070042
文摘Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.
文摘目前国内外对肾上腺皮质激素治疗重型肝炎的利弊存在一定的争议.但 Muto et al 报告,1993年从日本各大中心收集的数百例暴发性病毒性肝炎(相当于我国的急性重型肝炎),用激素疗法者占52.7%～61.2%.我们应用激素短程疗法治疗病毒性重型肝炎亦取得了一定的疗效,为进一步探讨其疗效机制,我们于1998-03/1999-06,对13例激素治疗的病毒性重型肝炎患者血清 TNFα和 sIL-2R 水平进行了观察.
基金ThisprojectwassupportedbytheNaturalScienceFoundationofChina(No 3 0 170 880 )andtheScienceCommitteeFoundationofJiangsuProvince (No BJ9810 0 )
文摘Background Dendritic cells (DCs) are the most powerful antigen-presenting cells to induce specific T-cell immunity, which plays an important role in the body’s anti-tumor responses. In this study, we assessed the feasibility and efficacy of inducing T-cell immunity against Epstein-Barr virus (EBV)-associated tumors in vivo using dendritic cells transfected with EBV latent membrane 2A (LMP2A) recombinant adenovirus.Methods Cytokine-activated bone marrow-derived DCs transfected with EBV LMP2A recombinant adenovirus were infused into BALB/c mice. Splenic cytotoxic T-cell responses were evaluated by cytotoxicity and interferon-γ production assays. in vivo immune protection was then assessed in the mice tumor models implanted with tumor cells expressing EBV LMP2A.Results DCs transfected with EBV LMP2A recombinant adenovirus could strongly induce EBV LMP2A-specific cytotoxic T-cell responses and upregulate interferon-γ production in vivo. Vaccination using these DCs led to prolongation of overall survival rates in the mice tumor models and retarded tumor growth. Conclusions The results suggest that DCs transfected with EBV LMP2A recombinant adenovirus can serve as a feasible and effective tool for eliciting LMP2A-specific cytotoxic T-cell responses against EBV LMP2A in vivo in the treatment of EBV-associated tumors.
