Jagadish Singh

Evaluation of antitumor activity of stigmasterol, a constituent isolated from Bacopa monnieri Linn aerial parts against Ehrlich Ascites Carcinoma in mice

Cancer remains as one of the most common cause of mortality worldwide. Cancer chemoprevention by natural products is well accepted nowadays. Phytoserols are natural products, showing anticancer activity, besides other activities. The purpose of this study was to examine the antitumor and antioxidant activity of stigmasterol, a phytosterol isolated from aerial parts of Bacopa monnieri Linn. against Ehrlich Ascites Carcinoma (EAC) in swiss albino mice. The effect of stigmasterol on the growth of transplantable murine tumor, life span of EAC bearing hosts, simultaneous alterations in the hematological profile, liver biochemical parameters (lipid peroxidation, antioxidant enzymes) and histopthological studies of liver were examined. Stigmasterol decreased tumor volume, packed cell volume and viable cell count, and increased mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to near normal levels in stigmasterol treated mice. Stigmasterol decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase in the liver of EAC bearing mice. Histopathological study of liver tissues showed that stigmasterol had significant protective effect against EAC bearing mice, which corroborates the above findings. Lactate dehydrogenase (LDH) activity in ascitic fluid increased while membrane microviscosity of the EAC cells decreased upon stigmasterol treatment indicating its effect in the membrane integrity functions. The antitumor activity of stigmasterol might be mediated through the activation of protein phosphatase 2A by ceramide causing apoptosis, as is shown by structurally similar phytosterol.

Antihyperglycemic activity of bacosine, a triterpene from Bacopa monnieri, in alloxan-induced diabetic rats.

This article describes the antihyperglycemic activity, in vivo antioxidant potential, effect on hemoglobin glycosylation, estimation of liver glycogen content, and in vitro peripheral glucose utilization of bacosine, a triterpene isolated from the ethyl acetate fraction (EAF) of the ethanolic extract of Bacopa monnieri. Bacosine produced a significant decrease in the blood glucose level when compared with the diabetic control rats both in the single administration as well as in the multiple administration study. It was observed that the compound reversed the weight loss of the diabetic rats, returning the values to near normal. Bacosine also prevented elevation of glycosylated hemoglobin in vitro with an IC₅₀ value of 7.44 µg/mL, comparable with the one for the reference drug α-tocopherol. Administration of bacosine and glibenclamide significantly decreased the levels of malondialdehyde (MDA), and increased the levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the liver of diabetic rats. Bacosine increased glycogen content in the liver of diabetic rats and peripheral glucose utilization in the diaphragm of diabetic rats in vitro, which is comparable with the action of insulin. Thus, bacosine might have insulin-like activity and its antihyperglycemic effect might be due to an increase in peripheral glucose consumption as well as protection against oxidative damage in alloxanized diabetes.

Isolation and in vivo hepatoprotective activity of Melothria heterophylla (Lour.) Cogn. against chemically induced liver injuries in rats

OBJECTIVE To investigate hepatoprotective activity of ethanol extract of Melothria heterophylla Lour Cogn. (EEMH) against CCl(4)-induced hepatic damage in rats. METHODS β-sitosterol was isolated by column chromatography and characterized spectroscopically. Two different doses (200 and 400 mg/kg bw) of EEMH were administered orally in alternate days. The hepatoprotective activity was studied in liver by measuring biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total protein and total bilirubin. Lipid peroxidation product and different antioxidant enzyme activities were assessed in liver homogenate. RESULTS EEMH reduced all biochemical parameters and lipid peroxidation, as well as it increased the antioxidant enzyme activities in comparison with silymarin. The protective effect of the extract on CCl(4) induced damage was confirmed by histopathological examination of the liver. CONCLUSIONS This result strongly supports the protective effect of EEMH against acute liver injury, and may be attributed to its antioxidative activity.

Correlation and Path Analysis in Bottle Gourd [Lagenaria siceraria (Mol.) Standl.]

Bottle gourd [Lagenaria siceraria (Mol.) Standl.] is one of the most important cucurbit grown throughout the country for its tender fruits. It is also known as white flowered gourd or calabash gourd. It is a fast growing winter seasonal climbing annual, native to Africa. It is grown in both rainy and summer seasons and its fruits are available in the market throughout the year. It is a monoecious and highly cross-pollinated crop known to good potential for yield components.

1,3,4-Oxadiazoles as Telomerase Inhibitor: Potential Anticancer Agents

Cancer is a rapidly growing disease of current era which poses a major life threaten situation to human beings. Continuous research is going on in the direction to develop effective molecules for the treatment of the cancer. These efforts include searching of more active heterocyclic compounds possessing potential anticancer activity. The 1,3,4-Oxadiazole scaffold is a five member heterocyclic ring having versatile activities and created interest for synthetic organic and medicinal chemists for the designing of novel compounds having anticancer activity. The important mechanism behind tumor suppression by 1,3,4-Oxadiazole is related with the inhibition of different growth factors, enzymes and kinases etc. The current literature surveys revealed that 1,3,4-Oxadiazole is a promising lead for anti-cancer agents by the inhibition of telomerase activity. In cancerous cells telomerase enzyme is activated which maintains and restores the telomere which leads to cell proliferation. The telomerase inhibitors with enhanced specificity and improved pharmacokinetics have been considered for design and development of novel anti-cancer agents. This review focuses primarily on telomerase enzyme its function and mechanism of action. It also describes the interaction of telomerase enzyme with 1,3,4-Oxadiazole inhibitors including their structure activity relationships (SARs). With the knowledge of this molecular target, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer agents.

SYNTHESIS AND ANTICANCER ACTIVITY OF SOME 1, 3, 4-OXADIAZOLE DERIVATIVES AGAINST EHLIRCH ASCITES CARCINOMA BEARING MICE MODEL

Summary Five Schiff bases of 2-amino-5-aryl-1, 3, 4-Oxadiazole derivatives (a-e) have been synthesized starting from aromatic benzaldehyde. All five compounds have been prepared by using known reaction. The structures of the final compounds were determined by using IR, 1 H NMR Spectroscopy. The evaluation of anticancer activity was done against Ehrlich Ascites Carcinoma bearing albino mice. The synthesized compounds (a-e) were administered intraperitonially at the dose of 25 mg/kg; body weight per day for 7 days after 24 hour of tumor inoculation in mice. The standard compound used was 5-Fluorouracil (20mg/kg; body weight).The drug (a-e) treated groups exhibited decreased in body weight, tumor volume, packed cell volume, viable cell count and increased the tumor inhibition (%), tumor cells inhibition (%), nonviable cell count of EAC tumor bearing mice when compared with the EAC treated control group. The anticancer activity of synthesized (a-e) compounds has not yet been evaluated. The result of the present investigation may encourage us to develop and / improve similar other related compounds and test them for anticancer activity.T role of natural products as the valuable source of structurally diverse compounds possessing therapeutic potential for the treatment of human diseases and disorders has gained incredible interest in the last few decades. More and more doctors, researchers and scientists are looking for novel compounds focusing on plants used in traditional medicine. Recently a large number of studies have been reported on the benefits of natural products which are present in high quantities in medicinal and aromatic plants, fruits and vegetables. This harangue will concentrate on an assortment of theme related to the use of natural products in cancer chemoprevention, distinct chemical substances derived from plants that are considered as anticancer agent, simple synthetic modifications or copies of the naturally occurring substances, structural optimization of derivatives or analogues to stop carcinogenesis, association of anti-inflammatory, antioxidant and radical scavenging properties of natural products with reduced risk of cancer and innovation and extent of natural products to act as potential chemopreventive and/or chemotherapeutic agents. In addition, attendees of this talk will be accustomed with the efficacy of natural products against carcinogenesis, latest research in cancer chemoprevention and treatment using natural products, pertinent molecular mechanisms involved in the pharmacological effects of natural products, challenges and opportunities.C cytology (CVC) evaluated by the current methodologies, such as the bethesda system, has low sensitivity and high false negative rates. One of the categories used for CVC diagnosis is ASCUS, which represents a nonspecific category under which intraepithelial lesions of low or high grade can be easily masked, evidentiating the importance of establishing an objective and reproducible method for determining the degree of differentiation of cervical squamous epithelial cells. In a previous work developed by Rodriguez et al., a new diagnostic method based on fractal geometry was developed to quantitatively differentiate normal cells from cells with low-grade lesions, based on the mathematical concept of intrinsic mathematical harmony (IMH) and variability of fractal dimension. In the present work, starting from fractal geometry and the concepts of IMH and cellular variability there were developed computational simulations of possible paths that could be taken by the squamous cervical cells from a normal stage to malignity. For this purpose, there were selected 10 normal cells, and 3 geometric variations of each one were made in the box counting space from normality to H-SIL, maintaining cellular IMH of each state, according to the developed diagnostic method. The simulations included relationships corresponding to the state called ASCUS, whose mathematical values can be normal or of L-SIL. The simulations obtained of possible paths from normality to ASCUS, L-SIL and H-SIL constitutes quantitative, objective and reproducible measures that evidence a fractal organization in the cellular architecture.Each year, about 22,000 women in the United States are diagnosed with ovarian cancer. In theUnitedStates, ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death, after lung and bronchus, breast, colorectal, and pancreatic cancers. Ovarian cancer causes more deaths than any other cancer of the female reproductive system, but it accounts for only about 3% of all cancers in women. Metastatic ovarian tumors are thought to account for 10–30% of malignant ovarian tumors; it is difficult to determine the precise incidence of ovarian metastasis.Most metastatic ovarian tumors originate from the gastrointestinal tract, breasts, and gynecologic organs. The pathway of cancer cell metastasis from no gynecologic cancer to the ovary remains unclear except for the case of direct dissemination. The 5-year survival after resection of metastaticovarian tumor is 19%.Besides primary ovarian malignancies, the ovaries are also a frequent location of metastasis from other malignant primary tumors. Most cases of metastases to the ovary originate from the gastrointestinal (GI) tract, breast, and other gynecologic organs. Management and treatment of metastatic ovarian cancer is a challenge.RNA-based therapeutics has been developed as a potentialtherapeutic agent to treat human diseases including cancer. RNA molecules such as siRNA and miRNA are highly effective therapies for cancer, as it silences the expression of cancer-related genes/ selectively regulate the pathways that are involved in the development and progression of cancer. It has been shown that, inhibition of c-Myc, MDM2, and VEGF protein expression by siRNA formulated with tumor-targeting scFv modified LPH nanoparticles markedly suppressed B16F10 metastatic tumor growth. Thiswas achieved by codelivering of miRNA and siRNA in the LPH formulation, the combination strategy is effective to trigger an enhanced therapeutic effect. This methodology of the formulation modified with tumor-targeting scFv is highly effective for delivery of siRNA or miRNA into the affected body organ(s) in patients with ovarian cancer metastasis.scFv has several advantages over the conventional monoclonal antibody or small molecule as a target moiety for drug/gene delivery to cancer. They include profound penetration into the tumor site, high specificity, strong affinity, low toxicity, and weak induction of the unwanted immune response. Nanoparticles modified with GC4 scFv may be internalized by the cells through receptor-mediated endocytosis. miRNA, a potential therapeutic agent, regulates cellular behavior via specific targeting and downregulating mRNAs by nearly perfect base pairing. It has been reported that certain miRNAs are involved in the oncogenic and tumor suppressor networks and can potentially inhibit tumorgenesis. The miR-34a was found to suppress tumor proliferation and migration and cause apoptosis in cancer cells by activating p53 and downregulating c-Met and E2F3. In addition, it was shown that miR-34a induced apoptosis, suppressed the survivin expression and inactivated MAPK pathway in cancer cells. The LPH nanoparticle formulation for RNA-based metastatic ovarian cancer therapy is potentially suitable for clinical use due to its reduced toxicity. Moreover, the ability of the nanoparticles to target tumor site further increases the therapeutic value of the RNA therapeutics. It is noted, that the capacity to deliver siRNA and/or miRNA with a single formulation simultaneously targeting several different oncogenic pathways is an important advantage of the current approach. To conclude, this co-delivery of miRNA and siRNA has the potential of development therapeutic agent for metastatic ovarian cancer.L cancer is a major cause of cancer deaths throughout the word but the complexity of apoptosis resistance in lung cancer is unclear. This study defined important roles for inducing apoptosis in A549 human lung cancer cell line with sea anemone venom. In our previous study we found Heteractis magnifica displayed cytotoxic and cytolytic activity on human lung cancer cell line. However the detailed mechanism underlying this process has not yet been elucidated. This study shows that chemopreventive action of venom from H. magnifica might be due to its ability to induce apoptosis and cell cycle arrest. H. magnifica venom inhibited the growth of A549 cells line in a concentration dependent manner. The venom at 40 μg/ml on A549 cell line induced 32.2% apoptosis compared to 2.2% in untreated cells. Caspase 3/7 assay and JC-1 staining detected increases in the levels of apoptosis-regulating proteins and mitochondrial membrane potential, respectively. The findings of this study indicate that the crude extracts from H. magnifica induce apoptosis in A549 human lung cancer cell line and that this phenomenon is mediated via both the death receptor-mediated and mitochondria-mediated apoptotic pathway. Thus, novel compounds from H. magnifica may be developed as effective treatments for lung cancer.Introduction: The incidence of renal cell carcinoma cases diagnosed in the elderly population (≥65 years-old) is rising as a result of an increasing life expectancy. Up to the end of the last decade cytokine-based therapy was the only, even if only moderately effective systemic therapy. The treatment of mRCC has changed dramatically over the past few years: targeted therapies have fundamentally altered the therapy of mRCC. Despite this, the role of targeted therapies is still poorly documented in elderly patients with metastatic renal cell carcinoma (mRCC). The aim of this study is to evaluate the outcome of target therapies in elderly patients in daily clinical practice after the era of cytokine-based therapy in mRCC. Materials and Methods: We retrospectively analyzed all consecutive elderly patients with mRCC treated at clinical oncology unit of the University Hospital of Ferrara (Italy) from June 1998 to September 2010. We divided the general case study into 2 subgroups: patients treated only with immunotherapy and patients treated with targeted therapies in first or subsequent lines and we compare results in term of overall survival (OS), censoring surviving patients at the time of last follow-up, with statistical significance (p<0.05) of differences evaluated by log-rank test; the initial date for survival was calculated from the date mRCC was first recognized. Results: Among 61 patients affected by mRCC treated in the same period at our Clinical Oncology Unit, 27 patients (44.3%) were elderly patients: 13 patients (48.1%) were treated with only cytokine-based therapy and 14 patients (51.9%) were treated with target therapies in first line or subsequent lines. At last follow-up (September 2010), 6 patients (22.2%) were alive with metastasis, 19 patients (70.4%) were deceased and 2 patients (7.4%) were lost during follow-up (PFU). Median time follow-up was 19.3 months (range 2.1-70.3). For patients treated with only immunotherapy (especially in early years, before 2007) median time follow-up was 28.6 months (range 2.1-70.4) and for patients treated with target therapies (especially in late years, after 2007 for patients with previous treatment for mRCC) median time follow-up was 15.3 months (range 5.8-54.8). Median age was 70.0 years (range 65-81 years). Twenty (74.1%) were “young-old” patients (65≤x<74 years old) and 7 patients were “old-old” (75≤x<84 years old); there were not “oldest-old” patients (≥85 years old). The general case study is summarized on Table 1. Median OS for patients treated only with immunotherapy was 29.2 months (95% Confidence Interval: 9.8-48.5). Median OS for patients with target therapies was 19.8 months (95% Confidence Interval: 11.1-28.5). By the univariate analysis there was no statistical significance difference in OS (p=0.900) between the two subgroups Conclusion: The incidence of mRCC in elderly patient is high in the clinical practice. Our data do not seem to confirm a significant impact in terms of survival atfer the introduction of target therapies in the elderly population. These results probably confirm the need for a longer follow-up before we can draw conclusions on the actual impact of the introduction of targeted therapies in this subgroup. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy.Introduction: Women are potential consumers of health care services. Critical consideration has been dedicated to women’s participation in breast cancer prevention but our knowledge about a link between breast health-seeking behaviours and community participation in breast cancer prevention remains incomplete. Understanding human behaviour is precondition to change behaviour and improve community participation in health. This study starts with the assumption that there is a need to develop a model for understanding breast health-seeking behaviour (e.g. mammography screening) among women (health consumers) in order to explore their participation in prevention programs. Purpose: This study attempts to understand individual health-seeking behaviour as a tool for explaining how health consumers engage with health services or preventive activities which is a first attempt in a less developed countries such as Iran. Methods: To come up with the model, an assessment framework was developed based on three theoretical underpinnings namely the health belief model, the theory of reasoned action and the social cognitive theory with the purpose of identifying the significant psycho-social factors influencing breast health behaviour among women. This model also focused on a typology of community participation approaches in health, as well as five levels of participation in health programs proposed by Rifkin. The model explains the practical aspect of community participation for breast cancer prevention in developing and less developed countries. Results: This result was concluded on the basis of empirical evidence presented in the recent study regarding women’s participation in breast cancer prevention programs or activities in Iran. We have demonstrated that more positive belief, greater social influence, and lower barriers toward preventive health behaviours (e.g. mammography use) can motivate women to be involved in health activities. Contrary to earlier expectations, self efficacy was not significantly related to the higher level of participation. In the study, community participation exhibits at a health benefit and program activity levels. In fact, this study showed what seems to have been changed is the need to shift from community involvement to meaningful participation in decision-making processes. However, the study highlighted that women have some preliminary problems in the acceptance of prevention techniques like mammography use, so their involvement or participation is mostly originated from health information sharing by professionals. Despite the limited levels of participation, we can describe that community participation may benefit with or without health professionals if the community decide to do preventive behaviours. Conclusion: Drawing attention to the current practice of need for breast health-seeking behaviour prior to community participation in breast cancer prevention will help to reduce delayed diagnosis of breast cancer among women, to improve treatment, and to develop health promotion strategies in a variety of context. More effort should be in placed to increase women’s awareness, psychosocial needs, and their willingness to cooperate with health professionals for breast cancer screening. Community involvement in preventive health behaviours helps increasingly aware of voluntary participation in health promotion programs. This could be accomplished using a holistic model of community participation in breast cancer prevention through combining the individual and community concerns in designing an intervention program for promoting breast health behaviours among women. The presentation of this model is not a chronological order of how these approaches of community participation have been expanded, but rather follows a logic means from individual participation to community participation in health showing how psycho-social factors adjust the different models and levels of participation. This initiative is about improving health status among women and acknowledges community development endeavor.Background: The Polycystic ovary syndrome (PCOS) is established in the presence of two of the three following criteria: clinical and / or biochemical hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology in ultrasound. Longterm metformin treatment may increase ovulation, improve menstrual cyclicity, and decrease androgen levels in these patients. Aim: The aim of this study was to investigate the effectiveness of short and long term metformin treatment in Iraqi PCOS women and the role of anti-mullerian hormone (AMH) levels in assessment of this treatment. Subjects and Methods: This study was carried out at biochemistry department, college of medicine, University of Baghdad, Iraq. It included twenty PCOS women aged (18-38 year) studied on cycle day (cd) from 2-4 (group I). These women were followed up after they were used metformin hydrochloride tablet 500 mg three times daily for 3 months (and considered as group II). Moreover, 18 PCOS women aged (22-36 year) who were already on metformin hydrochloride treatment 500 mg tablet three times daily for 6 months to 3 years and was studied on cd 2-4 ( and considered as group III). Serum investigations included measurements of AMH, FSH, LH, Free Testosterone, E2, prolactin and 17alpha hydroxyprogesterone. Furthermore, ultrasonic study included ovarian volume and number of ovarian follicles was also studied. Results: The mean (±SEM) value of serum AMH levels was significantly decreased in group II with short term metformin treatment when compared with that of Group I PCOS women before treatment (P<0.01). In addition, the mean of serum AMH levels of group II was insignificantly reduced in comparison with that of Group III long term treatment (P>0.05). However, there was no significant difference in serum AMH mean value between Group I and Group III. Conclusions: This study revealed the effectiveness of three months short term metformin treatment in Iraqi PCOS women and the efficacy of serum AMH measurement in evaluation of this treatment. Long term metformin treatment of more than 3 months has no advantage over that of short treatment in correction of PCOS condition.G colonization by Helicobacter pylori increases the risk of atrophic gastritis and gastric cancer. Serum levels of pepsinogen I and gastrin-17 which are respectively biomarkers of corpus and antrum mucosal activity are well known parameters of atrophic gastritis. We examined the diagnostic efficacy of GastroPanel serological kit (pepsinogen I& II, gastrin-17 and H. pylori IgG), in diagnosing and scoring atrophic gastritis. Dyspepsia patients undergoing gastroscopy with biopsy were recruited prospectively on voluntary basis at the Yaounde Central and University Teaching Hospitals, from March to July 2011. The degree of atrophy was classified according to levels of serum pepsinogen I &II, gastrin-17 and H.pylori IgG and compared with histological profiles. 86 volunteers aged 21 to 83, mean ± C.I. (46.4±3.3) were enrolled. The prevalence of gastritis was statistically similar between GastroPanel test and histology (89.5% versus 83.7%: p>0.20). However, the GastroPanel diagnosed more atrophic gastritis than histology (17.4% versus 7.0%: p 0.05). These results suggest that diagnosis of atrophic gastritis and H. pylori infection obtained with an optional serological method, GastroPanel is in strong agreement with biopsy findings, and thus can be a useful non-endoscopic assessment of stomach mucosal atrophy in patients with dyspepsia.With the aging and growth of world population and high prevalence of unhealthy behaviors and lifestyles, colorectal cancer (CRC) has become a big burden on global health. CRC is associated with multiple risk factors and its risk factors vary by population which makes intervention very difficult in the general population. Mass CRC screening is effective in reducing CRC mortality and incidence among asymptomatic individuals in the community although the magnitude of effectiveness is small due to many barriers. Based on current literature evidence and the fact of economic crisis, the editorial depicted the perspectives of mass CRC screening and early clinical diagnosis. A currently cost-effective and feasible Risk-Stratification-Based mass CRC screening protocol for CRC early detection and prevention is recommended and emphasized especially benefiting medically and economically underserved populations/areas. Existing issues for future research including urgent needs of serum biomarker and more efficient screening protocol for mass CRC screening are discussed.Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutated form of HSP 110 (HSP110DE9) in colorectal cancer displaying microsatellite instabi lity (MSI CRC), generated from an aberrantly splice d mRNA and lacking the HSP110 substrate binding domain. This mutant is expressed at variable levels in MSI CRC cell lines and primary tumors. HSP110DE9 impaired both the normal cellular localiz ation of HSP110 and its interaction with other HSPs , thus abrogating the chaperone activity and anti-apoptotic function of HSP110 in a dominant negative manner. HSP110DE9 overexpression caused the sensitization of cells to anticancer age nts such as oxaliplatin and 5-fluorouracil which ar e routinely prescribed in the adjuvant treatment of CRC patients. The expression level of mutant HSP110 correlates wi th the size of allelic deletions in the HSP110 T17 DNA repeat located in intron 8. We recently examined a consecutive, multi centre series of 329 patients with stage II or stag e III CRC whose positive MSI status was prospectively identified at diagnosi s using standardized methods. Both stage II and sta ge III CRC patients with large HSP110 T17 deletions and who received adjuvant chemotherapy s howed excellent relapse-free survival regardless of the regimen used. Multivariate models confirmed that the survival of stage III MSI CRC patients and of chemotherapytreated MSI CRC patients was dependent on the mutat ion s atus of HSP110 T17. Mutations in HSP110 T17 thus predict the outcome of patients with MSI CRC. The likely mechan ism for this association is the chemosensitization of cancer cells following the loss of HSP110 chaperone function.T lecture will address the debated role of cytomegalovirus (CMV) replication for the outcome of patients with B-cell lymphomas undergoing allogeneic hematopoietic stem cell transplantation (HSCT). CMV replication can cause multi-organ disease, which is usually associated with acute or chronic graft-versus-host-disease (GVHD), suppression of graft hemopoiesis and immunosuppression, and eventually results in higher non-relapse mortality (NRM). However, it was recently reported that post-transplant CMV replication was associated with a reduced risk of relapse for patients with acute myeloid leukemia. We therefore investigated the role of CMV replication in a retrospective cohort, from seven different Italian institutions, of 200 patients with B-cell lymphomas and transplanted with a similar conditioning regimen comprising the association of thiotepa and cyclophosphamide. In univariate analysis we found that CMV replication was associated with a reduced risk of lymphoma relapse especially for patients transplanted from a HLA identical sibling and with a disease in complete remission post-transplant. Multivariate analysis showed a more complex role for CMV replication that substantially influenced the NRM rate. This lecture will focus also on recent findings of different subsets of the immune-system activated by CMV replication and that might be involved in the reduced relapse rate of lymphoma patients. In particular the lecture will focus on NK and gamma-delta T cells and will propose some pre-clinical mouse models to investigate the potential connection between CMV replication and graft versus lymphoma (GVL) effect.E evidence suggests that supernumerary centrosomes drive chromosomal instability and is linked to oncogenesis. We have recently characterised a novel cellular centrosomal protein, which we named TAX1BP2 and have shown to play an important role in centrosome duplication. TAX1BP2 is targeted by human T cell leukaemia virus (HTLV-I) to create chromosome instability and aneuploidy. While aneuploidy is frequently observed in human liver cancer, we hypothesize that dysregulation of TAX1BP2 plays a role in the hepatocarcinogenesis. Using quantitative RT-PCR, our data has suggested that TAX1BP2 was frequently lost in human HCC. The underexpression of TAX1BP2 transcript was significantly associated with shorter overall survival rates, thus a poorer prognosis, in HCC patients. Furthermore, we demonstrated that TAX1BP2 is regulated by CDK2 kinase and the regulation of TAX1BP2 by CDK2 is tightly linked to the upregulation of tumor suppressor, p53. Thus, we propose that TAX1BP2 is a novel tumor suppressor in liver cancer.METHODOLOGY This descriptive analytical study determines knowledge, attitudes and acceptability of HPV vaccination amongst primary school girls aged ≥ 9 years in Minakulu Sub County, Oyam district-Northern Uganda. Systematic sampling of 415 pupils and 5 purposively selected key informants was conducted using semi structured questionnaires. Quantitative data was analyzed using SPSS 16.0. Directed content analysis of themes of transcribed qualitative data was conducted manually.