Kenneth Alibek

Role of infectious agents in the carcinogenesis of brain and head and neck cancers.

This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV) in distinct types of brain tumour, namely glioblastoma multiforme (GBM) and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC). Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV) and head and neck squamous cell carcinoma (HNSCC); specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90%) and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of infection in carcinogenesis of brain and head and neck cancers. We review recent studies on the infectious origin of these cancers and present our current understanding of carcinogenic mechanisms, thereby providing possible novel approaches to cancer treatment.

Role of viruses in the development of breast cancer.

The most common cancer worldwide among women is breast cancer. The initiation, promotion, and progression of this cancer result from both internal and external factors. The International Agency for Research on Cancer stated that 18-20% of cancers are linked to infection, and the list of definite, probable, and possible carcinogenic agents is growing each year. Among them, biological carcinogens play a significant role. In this review, data covering infection-associated breast and lung cancers are discussed and presented as possible involvements as pathogens in cancer. Because carcinogenesis is a multistep process with several contributing factors, we evaluated to what extent infection is significant, and concluded that members of the herpesvirus, polyomavirus, papillomavirus, and retrovirus families definitely associate with breast cancer. Detailed studies of viral mechanisms support this conclusion, but have presented problems with experimental settings. It is apparent that more effort needs to be devoted to assessing the role of these viruses in carcinogenesis, by characterizing additional confounding and synergistic effects of carcinogenic factors. We propose that preventing and treating infections may possibly stop or even eliminate certain types of cancers.

The role of infectious agents in urogenital cancers

Since the late 1990s, infectious agents have been thought to play a role in the pathogenesis of approximately 15% of cancers. It is now widely accepted that infection of stomach tissue with the bacteria Helicobacter pylori is an important cause of stomach adenocarcinoma. In addition, oncogenic viruses, such as papilloma viruses, herpes viruses, and hepadnaviruses are strongly associated with increased risk of cervical cancer, lymphomas, liver cancer, amongst others. However, in the scientific community the percentage of cancers caused by pathogens is believed to be far higher than 15%. A significant volume of data collected to date show an association between infectious agents and urogenital cancers. These agents include Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium and certain viruses that have been implicated in ovarian cancer. Other pathogens include the hepatitis C and Epstein-Barr viruses, which are potentially involved in kidney cancer. In addition, infections with Schistosoma haematobium, the human papillomavirus, and human polyomaviruses are strongly associated with an increased risk of urinary bladder cancer. This article reviews publications available to date on the role of infectious agents in urogenital cancers. A greater understanding of the role of such agents could aid the identification of novel methods of urogenital cancer treatment.

Implication of human herpesviruses in oncogenesis through immune evasion and supression

All human herpesviruses (HHVs) have been implicated in immune system evasion and suppression. Moreover, two HHV family members, i.e. EBV and KSHV, are recognised as oncogenic viruses. Our literature review summarises additional examples of possible oncogenic mechanisms that have been attributed to other HHVs. In general, HHVs affect almost every cancer-implicated branch of the immune system, namely tumour-promoting inflammation, immune evasion, and immunosuppression. Some HHVs accomplish these effects by inhibiting apoptotic pathways and by promoting proliferation. Mechanisms related to immunosupression and low grade chronic inflammation could eventually result in the initiation and progression of cancer. In this article we open a discussion on the members of Herpesviridae, their immune evasion and suppression mechanisms, and their possible role in cancer development. We conclude that discerning the mechanisms of interplay between HHV, immune system, and cancer is essential for the development of novel preventative and therapeutic approaches for cancer treatment and prophylaxis.

Pathogen-driven gastrointestinal cancers: Time for a change in treatment paradigm?

The regulation of cancerous tumor development is converged upon by multiple pathways and factors. Besides environmental factors, gastrointestinal (GI) tract cancer can be caused by chronic inflammation, which is generally induced by bacteria, viruses, and parasites. The role of these inducers in cancer development, cell differentiation and transformation, cell cycle deregulation, and in the expression of tumor-associated genes cannot be ignored. Although Helicobacter pylori activates many oncogenic pathways, particularly those in gastric and colorectal cancers, the role of viruses in tumor development is also significant. Viruses possess significant oncogenic potential to interfere with normal cell cycle control and genome stability, stimulating the growth of deregulated cells. An increasing amount of recent data also implies the association of GI cancers with bacterial colonization and viruses. This review focuses on host-cell interactions that facilitate primary mechanisms of tumorigenesis and provides new insights into novel GI cancer treatments.

Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer

The Bcl proteins play a critical role in apoptosis, as mutations in family members interfere with normal programmed cell death. Such events can cause cell transformation, potentially leading to cancer. Recent discoveries indicate that some viral proteins interfere with Bcl proteins either directly or indirectly; however, these data have not been systematically described. Some viruses encode proteins that reprogramme host cellular signalling pathways controlling cell differentiation, proliferation, genomic integrity, cell death, and immune system recognition. This review analyses and summarises the existing data and discusses how viral proteins interfere with normal pro- and anti-apoptotic functions of Bcl-2 and Bcl-xL. Particularly, this article focuses on how viral proteins, such as Herpesviruses, HTLV-1, HPV and HCV, block apoptosis and how accumulation of such interference predisposes cancer development. Finally, we discuss possible ways to prevent and treat cancers using a combination of traditional therapies and antiviral preparations that are effective against these viruses.

Weight change therapy as a potential treatment for end-stage ovarian carcinoma

Patient: Female, 41 Final Diagnosis: Ovarian carcinoma Symptoms: Ascites • hepatomegaly • weight loss Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual or unexpected effect of treatment Background: The aim of this case report is to present the results of treatment of end-stage ovarian carcinoma in a 41-year-old women using weight loss therapy. Case Report: We describe the case of a female aged 41 years with epithelial invasive ovarian cancer of III–IV stage, T3N2M1. Concurrent diseases were: abdominal carcinomatosis; hepatomegaly; ascites; condition after laparocentesis and skin-abdominal fistula; condition after 6 courses of neo-adjuvant polychemotherapy; hypertension II stage, risk factor of 3–4; dyslipidemia; and metabolic syndrome. A weight loss method based on a very-low-calorie diet and physical activity was used. Body weight was reduced from 74 kg to 53 due to loss of adipose tissue after 6 months of therapy. At the same time, the percentages of water and muscle tissue were increased significantly. While overweight was reducing, clinical, laboratory, and instrumental results were improving. As a result of the weight loss therapy, about ≈100 mm-sized ovarian cancer was transformed into smaller-sized ovarian cysts. Conclusions: An analgesic effect was also achieved without use of narcotic or non-narcotic analgesics. These cyto-reversible processes were documented by laboratory and instrumental data. The mechanisms behind these differences remain to be elucidated. Future research with a larger study cohort and longer follow-up is needed to further investigate the role of caloric restriction diet in cancer cell changes in ovarian cancer.

Measuring the Implications of the D-Basis in Analysis of Data in Biomedical Studies

We introduce the parameter of relevance of an attribute of a binary table to another attribute of the same table, computed with respect to an implicational basis of a closure system associated with the table. This enables a ranking of all attributes, by relevance parameter to the same fixed attribute, and, as a consequence, reveals the implications of the basis most relevant to this attribute. As an application of this new metric, we test the algorithm for D-basis extraction presented in Adaricheva and Nation [1] on biomedical data related to the survival groups of patients with particular types of cancer. Each test case requires a specialized approach in converting the real-valued data into binary data and careful analysis of the transformed data in a multi-disciplinary environment of cross-field collaboration.

The effects of antiviral treatment on breast cancer cell line

BackgroundRecent studies have revealed the positive antiproliferative and cytotoxic effects of antiviral agents in cancer treatment. The real effect of adjuvant antiviral therapy is still controversial due to the lack of studies in biochemical mechanisms. Here, we studied the effect of the antiviral agent acyclovir on morphometric and migratory features of the MCF7 breast cancer cell line. Molecular levels of various proteins have also been examined.MethodsTo evaluate and assess the effect of antiviral treatment on morphometric, migratory and other cellular characteristics of MCF7 breast cancer cells, the following experiments were performed: (i) MTT assay to measure the viability of MCF7 cells; (ii) Colony formation ability by soft agar assay; (iii) Morphometric characterization by immunofluorescent analysis using confocal microscopy; (iv) wound healing and transwell membrane assays to evaluate migration and invasion capacity of the cells; (v) ELISA colorimetric assays to assess expression levels of caspase-3, E-cadherin and enzymatic activity of aldehyde dehydrogenase (ALDH).ResultsWe demonstrate the suppressive effect of acyclovir on breast cancer cells. Acyclovir treatment decreases the growth and the proliferation rate of cells and correlates with the upregulated levels of apoptosis associated cytokine Caspase-3. Moreover, acyclovir inhibits colony formation ability and cell invasion capacity of the cancer cells while enhancing the expression of E-cadherin protein in MCF7 cells. Breast cancer cells are characterized by high ALDH activity and associated with upregulated proliferation and invasion. According to this study, acyclovir downregulates ALDH activity in MCF7 cells.ConclusionsThese results are encouraging and demonstrate the possibility of partial suppression of cancer cell proliferation using an antiviral agent. Acyclovir antiviral agents have a great potential as an adjuvant therapy in the cancer treatment. However, more research is necessary to identify relevant biochemical mechanisms by which acyclovir induces a potent anti-cancer effect.