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Patterns of Resection among Patients with Hepatic-Only Metastatic Colorectal Cancer a Single Institution Experience and Review

Problem statement: Hepatic-only metastasis in colorectal cancer is not a rare clinical finding and can account for 30% of cases. However, only 10-25% of cases are suitable for hepatic resection as part of their treatment pathway. We sought to document our own findings by reviewing patients with hepatic-only disease. Approach: A retrospective analysis was designed to include all patients seen at our institution from 1st January 2000 until 30th June 2010 and information as derived from the patients� records. Results: Forty-four (44) patients were found, with an average age of 60.8 years and a male preponderance. The majority of patients (approximately 57%) with hepatic-only metastases developed their disease following adjuvant therapy. Better overall survival was seen when a primary tumor had a low grade of histological differentiation and fewer than 3 hepatic lesions appreciated on conventional radiology. Better outcome was seen in patients who underwent hepatic resection. Conclusion: Patients with hepatic-only metastases are not uncommon within our institution. Hepatic resection afforded better outcome and compares favorably with published literature.

Maternal Infection and Neurodevelopmental Disorders in the Offspring

Problem statement: Neurodevelopmental disorders such as schizophrenia and autism have been attributed to both genetic and environmental factors. Whether and how maternal infection as an environmental factor contributes to the development of neurological abnormalities in the offspring remains to be clearly defined. Approach: The literature was reviewed to examine the relationship between maternal infection and neurological disorders such as schizophrenia and autism. Results: Both epidemiological and experimental animal studies had found strong support for maternal infection as a significant risk factor for neurodevelopmental disorders. There was also accumulating evidence that inflammatory cytokines and glucocorticoids might be important mediators of maternal infection-induced effects on the offspring. Other factors such as oxidative stress and hypoxia might also aggravate neurodevelopmental damages. Conclusion: Studies are accumulating to support the link between maternal infection and neurodevelopmental disorders. Mechanisms underlying the link are also unfolding. Future studies examining how maternal infection contributes to the development of different neurodevelopmental disorders can help in developing effective intervention strategies.

Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

Problem statement: Bladder cancer is a common urologic cancer and intravesical Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the mainstay in the treatment of superficial bladder cancer. However, the current BCG therapy is not desirable with respect to its efficacy and side effects. Interleukin (IL)-10, a T helper type (Th) 2 cytokine, plays an important regulatory role in bladder cancer immunosurveillance and BCG immunotherapy. Therefore, blocking IL-10 activity could be beneficial for bladder cancer patients undergoing BCG therapy. Approach: Treatment with intravesical BCG in combination with systemic IL-10 monoclonal antibody (mAb) specific for IL-10 neutralization or IL-10 receptor (IL-10R) blockage has been evaluated in preclinical bladder cancer models. Results: Addition of anti-IL-10 neutralizing mAb or anti-IL-10R1 mAb enhances BCG induction of Th1 immune responses and anti-bladder cancer immunity. Conclusion/Recommendations: BCG immunotherapy of bladder cancer can be enhanced by addition of IL-10 blocking mAb. Future studies should aim to explore the mechanisms underlying the induction of enhanced antitumor immunity by BCG combination therapy and develop therapeutic regimens for clinical evaluation of the safety and efficacy of BCG combination therapy.

The Impact of Helicobacter Pylori Infection on Lung Function and Severity of Bronchial Hyperresponsiveness in Subjects with Allergic Asthma

Problem statement: There is evidence that Helicobacter pylori (H. pylori) infection may modify immune response and decrease the risk of asthma and other allergic diseases, as well. Approach: To assess the impact of H. pylori infection on lung function parameters and severity of Bronchial Hyperresponsiveness (BHR) in subjects with allergic asthma. A cross-sectional study including 38 H. pylori positive subjects with allergic asthma (18 males and 20 females, aged 21-54 years) and an equal number of H. pylori negative subjects with allergic asthma studied as a control was carried out. The impact of H. pylori infection was assessed by comparison of mean values of spirometric parameters and BHR severity (measured by histamine challenge and expressed as provocative concentration of histamine that causes FEV₁ fell by more than 20% of its base value-PC 20) between two examined groups. Results: The mean values of spirometric parameters were similar in both examined groups. The mean PC20 was lower in the group of subjects with allergic asthma and serological evidence of exposure to H. pylori but statistical significance was not reached (2.89 Vs. 3.14 mg mL^-1, P > 0.05. Conclusion: Our findings indicate that in cross-sectional analysis there is no significant relation between H. pylori seropositivity and the values of spirometric parameters and the degree of BHR severity in subjects with allergic asthma.

Leukemia and Therapy

Problem statement: Leukemia is a cancer which linked intimately with the immune system. It is a group of heterogenous neoplastic disorder of white blood cells characterized by the uncontrolled proliferation and block in differentiation of hematopoeitic cells. Generally, leukemia can be classified into myeloid or lymphoid referring to the type of abnormal cell found most in the blood. Approach: Many drug discovery researches have utilized the leukemic cell lines to screen for their potential as chemotherapy agents for leukemia. Results: The understanding on the types of leukemia and current choice of chemotherapy drugs can help to select the best target cell lines to study and the most suitable chemotherapy drug as positive control. Conclusion/Recommendations: This review cover types of leukemia, current option of chemotherapy drugs and some potential cytotoxic and immunomodulatory natural products targeting leukemic cancer cell line.

Monoclonal Antibody-Based Therapeutics for Melioidosis and Glanders

Problem statement: Burkholderia Pseudomallei (BP) and B. Mallei (BM) were two closely related pathogenic gram-negative bacteria. They were the causative agents of melioidosis and glanders, respectively and are recognized by CDC as category B select agents. Significant efforts had been devoted to developing the diagnostic and therapeutic measures against these two pathogens. Monoclonal antibody-based therapeutic was a promising targeted therapy to fight against melioidosis and glanders. Valuable findings have been reported by different groups in their attempt to identify vaccine targets against these two pathogens. Approach: Our group has generated neutralizing Monoclonal Antibodies (MAbs) against BP and BM and characterized them by both in vitro and in vivo experiments. We present an overview of the MAb-based therapeutic approaches against BP and BM and demonstrate some of our efforts for developing chimeric and fully human MAbs using antibody engineering. Results: Throughout conventional mouse hybridoma technique and antibody engineering (chimerization and in vitro antibody library techniques), we generated 10 chimeric MAbs (3 stable MAbs and 7 transient MAbs) and one fully human MAb against BP and BM. In addition, we present the reactive antigen profiles of these MAbs. Our approaches had potentials to accelerate the development of therapeutics for melioidosis and glanders in humans. Conclusion: Our experience and findings presented here will be valuable for choosing the best antigenic targets and ultimately for the production of effective vaccines for these two pathogens.

Interplay of Cytokines and Chemokines in the Pathogenesis of Systemic Lupus Erythematosus

Problem statement: Dysbalance of T-helper-cell (Th) cytokines and chemokines was suggested to contribute to the pathogenesis of Systemic Lupus Erythematosus (SLE). Recent reports suggest the involvement of cytokines and chemokines in the pathogenesis of SLE, but their relationship with each other and particularly in the severity of disease, was not yet understood. We analyzed the interaction between cytokines and chemokines and their relationship with severity of disease in SLE. Approach: Serum levels of cytokines and chemokines were determined by ELISA and severity of disease were measured by by using SLE Disease Activity Index (SLEDAI) score. Results: The serum levels of cytokine (IL-2, IFN-γ, IL-6, IL-10 and IL-12) and chemokine (CCL2, CCL5 and CXCL10) were variably associated with disease activity in SLE patients. Strict interaction between cytokines and chemokines was observed in SLE patients. Interleukin-6 was positively correlated with CCL5 while IL-12 was also analogous correlated with CXCL10 in SLE patients. The kidney involvement in SLE patients was related with intense increased levels of cytokines (IFN-γ, IL-12) and chemokines (CCL2, CCL5 and CXCL10). Conclusion: These data suggest that interplay of cytokines and chemokines may be involved in the severity of disease. Also, a better understanding of the cytokines and chemokines interaction may likely to provide important clues to the pathogenic mechanism and pave the way toward more effective therapeutics.

Evaluation of Immunomodulatory Effect: Selection of the Correct Targets for Immunostimulation Study

Problem statement: Numerous plants or remedies that are traditionally used for various diseases had been claimed to maintain general good health, particularly the immune system. With the advanced understanding on immunology and ethnopharmacology, study on the interaction of this herb with the immune system is critical to understand the safety and its efficacy as a potent immunomodulatory agent. Approach: Selecting proper immune cells from a suitable immune organ allowed for the understanding on the mode of immunomodulation. Lymphocytes isolated from mammalian thymus, spleen and bone marrow represented great candidates for this immunomodulatory study. Results: A number of herbal extracts including that of Rhaphidophora korthalsii and compounds isolated from this plant, namely lectin and zerumbone, had been identified as potent immunostimulators. Conclusion/Recommendations: Future studies are needed to elucidate the mechanism underlaying activites of these immunomodulatory agents.

Evaluating the Effect of Booster Dose of Hepatitis B Vaccine in Low-and Non-Responders Healthcare Workers and the Role of some Host-Related Factors

Problem statement: Hepatitis B comprises one of the major health problems worldwide. Health Care Workers (HCW) are a group at risk for Hepatitis B Virus (HBV) infection. Infection with hepatitis B virus has become a vaccine-preventable disease. Vaccination against Hepatitis B Virus infection (HBV) is safe and effective. The aim of this study is evaluation the immunologic response of booster dose of Hepatitis B vaccine in none and low responder health care workers and effects of some host-related factors. Approach: In a cross sectional descriptive analytic study carried out on the medical staff of Tabriz Shahid Madani Hospital in 2009-2010, we evaluated the immunologic response of booster dose of Hepatitis B vaccine in none and low responder health care workers and effects of some host-related factors. Results: Of 331 studied health care workers, 123 people (37.2%) were male and 208 people (62.8%) female. The mean antibody titer in the studied medical staff was 304.07�199.98 IU L^-1 in the range of 0-1000 and median of 330. Dividing the antibody titer into three groups of �no response� (Titer<10 IU L^-1), �Low response� (Titer10-100 IU L^-1) and �Good response� (Titer>100 IU L^-1) revealed that from 331 studied staff, 31 people (9.4%) were in �no response� group, 40 people (12.1%) in �Low response� group and 260 people (78.59%) in �Good response� group and after one booster dose of vaccine in none and low responder group, 7 people (2.1%) were in �no response� group, 5 people (1.5%) in �Low response� group and 319 people (96.4%) in �Good response� group. Conclusion: One booster dose of vaccine in people with low and none Response to hepatitis B vaccination cause to significantly increase of antibody titer so that, Good response rate increase from 78.5-96.4% and low response rate decrease from 12.1-1.5% and none response rate decrease from 9.4-2.1%. Use one booster dose of vaccine recommended in people with antibody titer blow 100.

Immunologic Response to Hepatitis B Vaccine in Health Care Workers: A Screening Program and Evaluation of Some Host-Related Factors Role

Problem statement: To evaluation the immunologic response to hepatitis B vaccine in health care�s workers and effects of host-related factors? Approach: In a cross sectional descriptive analytic study carried out on the medical staff of Tabriz Shahid Madani Hospital in 2009-2010, we evaluated the immunologic response of the staff to vaccination against Hepatitis B and factors affecting it. Results: The mean antibody titer in the studied medical staff was 366.76�169.714 IU L^-1. 2.05% were in �no response� group, 1.46% in �Low response� group and 96.49% in �Good response� group. Conclusion: Immunological response in the smoking staff was significantly less (p < 0.001) but no significant difference was observed in the response between genders (p = 0.127) and no case of hyperlipidemia was reported. There was a significant reverse linear relation between age and antibody titer in the studied staff (p = 0.003, R = 0.162) but no significant linear relation was observed between weight, height and BMI and antibody titer.