Adil H. H. Bashir

Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer.

Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)

Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollos Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy.

Diabetes mellitus type 2 through oncology lens

Because metformin acts on both diabetic mellitus type 2 (DM type 2) and some types of cancers [1], metformin might be an indicator that cancer cells are naturally resistant to insulin. Thus, do DM type 2 and cancer are two faces of the same coin? In other words, does DM type 2 represent a silent form of cancer? Especially with recent publication hypothesizes that neoplasia can occur without dysplasia [2]. Recently, metformin has become an attractive agent that prevents and/or delays DM type 2 induced carcinogenesis through its activity in decreasing circulating insulin level [3–5] or direct anti-proliferative effect in vitro [6]. Poly cystic ovarian syndrome (PCOS) is explained currently via several theories but we are interested in only two of them: Firstly, it increases the level of testosterone in female that is why it responds to finasteride. Secondly, PCOS could be the results from insulin resistance so it responds to metformin and rosiglitazone [7–10]. Because metformin might precipitate male infertility [11], metformin has weak anti-androgenic activity. Therefore, it is an attractive agent against PCOS; it acts via insulin sensitization and it is equivalent to anti-androgenic too [12]. Interestingly, low testosterone level induces insulin resistance [13,14]. Plasma testosterone level in men with type 2 diabetes is lower than that of normoglycemic men and be improved after well controlled diabetes [15]. In addition, metformin decreases total testosterone level in obese men with type 2 diabetes; metformin with hypocaloric diet decreases free testosterone in obese nondiabetic men [11]. By now, metformin decreases insulin resistance via targeting AMPK and at the same time it can induce insulin resistance through decreasing level of testosterone which is compatible with Weiwei–Renming model. So, might the activity of metformin as an insulin sensitizer become conundrum? Activity of metformin against some metabolic disorders encourages us to pose additional important questions:

Primary Cutaneous Follicular Lymphoma Associated with Helicobacter pylori Infection

Background: Atopic dermatitis (AD) is one of inflammatory skin diseases that is characterized by intense pruritus and relapsable eczematous lesions. The hallmarks of AD are defects of epidermal barrier and immunoglobulin E (IgE)-mediated sensitization to several environmental allergens, and immune disorder mediated by an imbalance towards T-helper-2 (Th2) response. Melittin (Mel), a major component of Bee venom, has been studied in various inflammatory diseases including liver cirrhosis, atherosclerosis, and acne. However, beneficial effects of Mel on AD-like animal have not been explored. Therefore, we investigated the anti-atopic effects of Mel.A 66 year o ld male with a long standing uncontrolled gastric H pylori infect ion and Crohns disease presented with nodular lesions in the back. These were removed surgically. Pathologically the lesion consisted of ly mphocytes, giant cells with vacuolated cytoplasm and histiocytes. By immunohistochemistry there were stem cells, B cells and CD1a Langerhans cells. The diagnosis of Langerhans histiocytosis was made. The giant cells were positive for both CD 20 B cell marker and the macrophage marker CD 68 indicat ing that they were derived fro m B cells. They were strongly positive for H pylori antigen. A year later the patient reported with non-itching nodular lesions in the right flank. There was no ly mphadenopathy or Splenomegaly. A biopsy of the lesion showed a follicu lar center B cell ly mphoma. The tu mor cells were positive for H pylori antigen. He was treated for H pylori infection. He co mp letely recovered and was in good health a year later.

Dermatitis Herpetiformis (DH) in Association with H. pylori Infection: Description of a Case Report

Dermatitis herpetiformis (DH) is an autoimmune blistering disorder associated with a gluten-sensitive enteropathy (GSE), and is generally accepted as a cutaneous manifestation of celiac disease and is characterized by grouped excoriations; erythematous, urticarial plaques; and papules with vesicles. We reported an interesting case of adult DH occurred in a 30 year old Sudanese young adult with chronic inflammatory bowel disease, presented with typical string of pearls in the face, trunk and extremities for 2 months duration. The case is diagnosed and confirmed as DH where histopathologically shows a sub-epidermal bulla with microabscess formation, sigmoidoscopy and H. pylori ELISA test were positive IgA. Our case had an adult onset of presentation. Clinical features and histopathology are typical. It is associated of H. Pylori, although poorly responding to triple therapy (Doxycyclin 100 mg bid for 8 days, Cefixime 400 mg for 5 days and Rabeprazole as proton pump inhibitor (PPI) 20 mg for 28 days), but focusing as possible antigen was of paramount concern as possible causative antigen; as in this case all serological specific tests for Coeliac disease were negative. The case was considered to be the second case of DH with CIBD due to H. Pylori been reported in Sudan.