Antitumor effect of mIFN-λ3 in C57BL/6 mice model for papilloma tumors

Although several years have passed since the determination of the human papilloma virus (HPV) as the causative agent for cervical cancer, a definitive treatment has not yet been found. Interferon-alpha (IFN-α) immunotherapy is one of the promising methods for tumor treatment, although numerous side effects were observed in clinical trials. Recently, a new type of interferon, lambda-interferon (IFN-λ), has been discovered with fewer side effects than IFN-α since its receptor repertoire is limited. IFN-λ has a series of activities including antiviral, anti-proliferative and anti-tumor actions. In the present study, the effects of IFN-α and IFN-λ on the TC1 papilloma tumor model in C57BL/6 mice were evaluated. TC1 cells were injected into the mice subcutaneously. Upon tumor formation, murine IFN, mIFN-α and mIFN-λ, expression plasmids were injected intratumorally in combination or alone. The survival time and tumor size as well as apoptosis in tumors and NK cytoxicity were measured after three injections. As compared with the control group, the remarkable results especially in the group which received mIFN-α and mIFN-λ together were obtained for all of the measured parameters. Although IFN-λ is a new member of the interferon family and its properties should be studied in detail, the data obtained suggests that the use of IFN-λ especially in combination with IFN-α could be considered as an effective strategy for papilloma cervical cancer immunotherapy. © 2015, Pleiades Publishing, Inc

Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer

Background: Genistein (GEN), a naturally occurring flavonoid present in soy bean, has attracted scientific interest for its possible benefits in cancer. Objective: The potential immunomodulatory effects of genistein on the immune system and against TC-1 tumor cell line were evaluated in adult female C57BL/6 mice. Methods: Mice were treated with GEN 10 days before to 10 days after the tumor induction. Thirty days after the last GEN treatment, lymphocyte proliferation, Lactase Dehydrogenase (LDH) cytolytic activity and cytokine secretion were analyzed in GEN and control groups. Results: The results showed that ingestion of genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment with genistein also caused a significant increment in interferon gamma (IFN-γ). In addition, the treatment achieved significant therapeutic effect in tumor models compared to the control group. These results indicated that the effect of GEN on tumor growth may be attributed to its effect on lymphocyte proliferation, cytolytic activity and IFN-γ production. Conclusion: These results demonstrate that GEN exerts an immunomodulatory effect in a mouse model of Human Papillomavirus (HPV) associated-cervical cancer

Lambda phage nanoparticles for targetomics

The emerging aim of drug delivery requires the bioactive or therapeutic molecule to be protected from degradation and reach its target cell and intracellular location. Target specificity of nanoparticles is a prerequisite to attain the concentration of therapeutic agent required for therapeutic efficacy in the target tissue while minimising adverse effects on other parts of the body. Therefore, there is an urgent need for improvement of more effective drug delivery systems to direct the anticancer drugs to cancer cells, specifically. In the paper, we have described advantages of Lambda bacteriophage over other drug delivery vectors and proposed it as promising drug delivery vehicle. © 2012 Asian Network for Scientific Information

Study the effect of echinacea purpurea extract on cellular delayed type hypersensitivity and splenocyte proliferation in BALB/c mice

Objective: Purple cone flower plant (Echinacea purpurea) is one of the most important Herbal products in many countries. Up to now a lot of experiments demonstrated the controversial effects of this herb on immune system . In this research we study the in vivo and in vitro effect of Iranian E.purpurea extract on cellular immunity. Materials and Methods: At first we determined the lethal dose of E.purpurea extract after intraperitoneal injection in BALB/c mice. Then we made five groups of mice and treat them by four times intraperitoneal injection of 1 ml extract at different doses (0, 0.4, 2, 10 and 50 mg/ml) during two weeks. Splenocyte proliferation response to extract was assessed by MTT method. Delayed-Type Hypersensitivity (DTH) response was evaluated by priming mice with 1×108 Sheep Red Blood Cell (SRBC) injected subcutaneously in the back on day 7after treatment. Results: As a result no significant variation in weight and spleen index of test groups to control was observed. Splenocyte proliferation and DTH response of test groups to control increased significantly (p<0.05). Conclusion: However these data confirmed the results of previous studies, in addition presented the first results about significant increase in DTH response that could not be seen before. Scince the main reason of this difference refers to active compounds of herb extract, comparing effective component of this extract with that of E.purpurea cultivated in other geographical condition will consider as the next studies

Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of a DNA vaccine

We have investigated whether poly(I:C) Toll-like receptor 3 (TLR3) and resiquimod Toll-like receptor 7 (TLR7) agonists can serve as vaccine adjuvants and promote the efficiency of therapeutic DNA vaccination against tumors expressing the human papilloma virus 16 (HPV-16) E7 protein. For this purpose, C57BL/6 mice were inoculated with 2 × 105 TC-1 cells, and they were then immunized with HPV-16 E7 DNA vaccine alone or with 50 μg of resiquimod or poly(I:C) individually. We found that poly(I:C) and resiquimod could induce more antigen-specific lymphocyte proliferation and cytolytic activity compared to vaccination with E7 DNA alone. While E7 DNA had no significant inhibitory effect on tumor growth, co-administration of poly(I:C) and resiquimod with E7 DNA induced significant tumor regression. Peripheral and local cytokine assays demonstrated that co-administration of poly(I:C) and resiquimod with E7 DNA induced circulating antigen-specific IFN-γ and nonspecific intratumoral IL-12. TLR3 and TLR7 agonists can be used to enhance the immune response to DNA vaccine immunogens. Taken together, these data indicate that combined vaccination with DNA encoding HPV-16 E7 plus TLR agonists provides a strategy for improving the efficacy of a vaccine as a possible immunotherapeutic strategy for cervical cancer. © 2014 Springer-Verlag Wien

Echinacea purpurea polysaccharide reduces the latency rate in herpes simplex virus type-1 infections

Objective: During the latency period of herpes simplex virus type-1 (HSV-1), the virus can occasionally reactivate, travel back to the eye and cause recurrent ocular disease. As this condition arises from the ability of HSV-1 to produce a dormant infection, effective medication to prevent the virus enter a latent state should prevent it. In this study, we applied Echinacea polysaccharide (EP) fraction as prophylactic mediator for latency prevention. Methods: In order to investigate the protective properties of EP, we evaluated its immunostimulatory functions on different immune aspects that play important roles in latency prevention (particularly IFN-γ as one of the main indicators of cellular immunity and latency). Finally, we assessed establishment of latency by detection of thymidine kinase gene in trigeminal ganglia of BALB/c mice. Results: We demonstrated that EP promotes immune response, leading to a reduced latency rate, and it has a promising effect on latency prevention. Conclusion: EP was able to exert an antiviral action on the development of recurrent HSV-1 disease when supplied prior to infection. © 2009 S. Karger AG, Basel

Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16

Objective: Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage ('phage')-λ particles, rather than purified 'naked' DNA, have been described as highly efficient delivery vehicles for a DNA vaccine. Methods: In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system. Results: The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 1012 particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models. Conclusion: Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia. Copyright © 2010 S. Karger AG, Basel

Rubella seroprevalence among primary and pre- primary school pupils at Moi's Bridge location, Uasin Gishu District, Kenya

<p>Abstract</p> <p>Background</p> <p>Rubella is an infectious and generally mild childhood viral disease. The disease is of public health importance because infection acquired during early pregnancy often results in foetal abnormalities that are classified as congenital rubella syndrome (CRS). The burden of rubella infection in most developing countries in not well documented because of limited epidemiological data. However, availability of an effective vaccine has made it necessary to have all the countries with no routine vaccination schedule to evaluate the burden of disease in order to make informed decisions on rubella vaccination and strategy. To address this gap we conducted a study to determine age-specific rubella seroprevalence rates and related risk factors among primary and pre-primary school children in Uasin Gishu district, Moi's Bridge location of Kenya.</p> <p>Methods</p> <p>Subjects of the study were 498 pupils from seven primary schools aged 4–20 years. Questionnaire surveys with blood sampling were conducted between January to July 2005. Samples were tested for rubella specific IgG antibody using ELISA test kit (Enzygnost^®Behring, Germany).</p> <p>Results</p> <p>Overall, rubella seropositivity rate was 80% and it increased with age from 59% (among ages 4–6 years) to 94% (ages 14–20 years). Multivariate logistic regression analysis model, showed that age of child and ownership of a television set which is a proxy measure of socio-economic status of family were significantly associated with rubella seropositivity. The odds of rubella seropositivity in a child older than 13 years was more than that in children younger than 7 years (OR = 3.8 95% CI 2.56–5.78). The odds of rubella seropositivity in a child whose family did not own a television set was 3 times higher than that of child whose family owned a set (OR 3.06, 95% CI 1.17–7.97).</p> <p>Conclusion</p> <p>The study provides important and highly useful information on rubella age specific seroprevalence rates in Kenya. Advancing age was found to be associated with increased risk of rubella. Low socio-economic factors suggest an increased risk of infection in certain categories of society, and control measures need to target this. Overall, the findings can also be used by policy makers to model introduction of routine rubella vaccination in the country and also other developing countries facing similar challenges. More than half of the children got infected in pre-primary and efforts to control rubella should target pre-school children. These data provides pre-vaccination information that can be used to guide immunization strategy as well as to determine success of an immunization programme.</p

آپوپتوز: مرگ برنامهريزي شده سلولي

فرايند آپوپتوز يا مرگ برنامهريزي شده سلول به عنوان روشي حفاظت شده، تحت كنترل ژنهاست كه به منظور حذف سلولهاي ناخواسته يا غيرضروري در موجودات زنده به كار ميرود و در بسياري از مكانيسمهاي سيستم ايمني يا بيماريها مداخله ميكند. اصليترين تفاوت اين مسير با نكروز سلولي به عنوان مسير اصلي حذف سلولهاي ناخواسته، در عدم ايجاد التهاب و اثر محدود به سلولهاي هدف است . آپوپتوز در فرايندهاي مهم زيست شناختي مانند تكامل طبيعي، هومئوستاز بافتي، حذف سلولهاي تخريب شده يا آلوده به ويروس و حذف سلولهاي ايمني فعال شده عليه آنتي ژنهاي خودي نقش بسيار حياتي را بر عهده دارد. اين فرايند در تنظيم ميزان رشد، تكثير سلولها، تكامل و سلامت بدن بسيار مهم بوده و بروز بسياري از بيماريهاي اتوايميون، سرطانها و عفونتهاي ويروسي نتيجه عملكرد ضعيف يا مهار شدن پديده مرگ برنامه ريزي شده سلولي و Bcl- است. بنابراين هدف اصلي مطالعههاي آپوپتوزي، تمركز بر روي شناخت اجزاي مولكولي و مكانيسم هاي تنظيمي به خصوص خانواده 2 به عنوان مهمترين گروههاي تنظيمي است و اين اطلاعات كمك ميكند تا با به كارگيري عوامل درماني كه اين فرايند را مت أثر IAP خانواده ميكنند، درمان بيماريهاي تخريب عصبي و بيماريهاي تكثيري نظير سرطان دور از ذهن نباشد

Purification of Herpes Simplex Virus Type 1 for Production of High Titer Polyclonal Antibody against the Virus

ABSTRACT: Introduction & Objective: Herpes simplex virus type 1 infection is one of the most prevalent viral infections worldwide. Different methods are being investigated for the virus’ detection, prevention and therapy. The aim of the present study was to purify the virus and to produce a high titer polyclonal antibody against the virus. Materials & Methods: This experimental study was done in the Virology Department of Tarbiat Modares University from 2001 to 2002. Virus purification was done using serial dilution and plaque purification protocols. A single plaque was chosen and propagated, and the virus titer was determined. In inoculated animals, the titer of produced antibody against the virus was measured by virus neutralization test. Results: Using virus neutralization test, it was found that the high level of antibody has been raised in animals against the virus. Conclusion: Considering the preparation of high titer antibody against the virus, the produced antibody can be used for the development and optimization of different diagnostic methods