A novel synthetic C-1 analogue of 7-deoxypancratistatin induces apoptosis in p53 positive and negative human colorectal cancer cells by targeting the mitochondria: enhancement of activity by tamoxifen

The natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis plant, specifically induces apoptosis in many cancer cell lines. Unlike many other chemotherapeutics, PST is not genotoxic and has minimal adverse effects on non-cancerous cells. However, its availability for preclinical and clinical work is limited due to its low availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7-deoxypancratistatin with different modifications at C-1 were synthesized and screened for apoptosis inducing activity in human colorectal cancer (CRC) cells. We found that a C-1 acetoxymethyl derivative of 7-deoxypancratistatin, JC-TH-acetate-4 (JCTH-4), was effective in inducing apoptosis in both p53 positive (HCT 116) and p53 negative (HT-29) human CRC cell lines, demonstrating similar efficacy to that of natural PST. JCTH-4 was able to decrease mitochondrial membrane potential (MMP), increase levels of reactive oxygen species in isolated mitochondria, cause release of the apoptogenic factor cytochrome c (Cyto c) from isolated mitochondria, and induce autophagy in HCT 116 and HT-29 cells. Interestingly, when JCTH-4 was administered with tamoxifen (TAM), there was an enhanced effect in apoptosis induction, reactive oxygen species (ROS) production and Cyto c release by isolated mitochondria, and autophagic induction by CRC cells. Minimal toxicity was exhibited by a normal human fetal fibroblast (NFF) and a normal colon fibroblast (CCD-18Co) cell line. Hence, JCTH-4 is a novel compound capable of selectively inducing apoptosis and autophagy in CRC cells alone and in combination with TAM and may serve as a safer and more effective alternative to current cancer therapies.     

Factors of importance for self-reported mental health and depressive symptoms among ages 60-75 in urban Iran and Sweden

Scand J Caring Sci; 2011; 25; 696–705 Factors of importance for self‐reported mental health and depressive symptoms among ages 60–75 in urban Iran and Sweden Background: Depression is a common experience affecting 121 million people around the world. In high income countries, depression is one of the most common psychiatric conditions among the elderly. Studies show that immigrants are particularly at risk for mental ill health. Aim: This study investigates the self‐reported mental health among two Iranian groups; one born and residing in Iran and one consisting of Iranian immigrants in Sweden, as well as native Swedes living in Sweden. The study also aims to explore and compare self‐reported depressive symptoms among three groups. Methods: This study is based on a cross‐sectional design measuring self‐reported health with a study specific questionnaire. The programme SPSS V.17.0 was used for all statistical analyses. Findings: 1088 participants were approached (668 Iranians in Iran; 105 immigrated Iranians in Sweden; and 305 Swedes in Sweden). Factors effecting self‐reported mental health was self‐reported health, smoking, satisfaction with social life and also a sense of connection to ones cultural roots and traditions. Also demographic variables such as group belonging (Swedes vs. Iranians), sex and satisfaction with Income were shown to be important when performing the regression analysis. In the chi‐square analysis the Iranian samples reported depressive symptoms to a larger extent than the Swedish group in all aspects of self‐reported depressive symptoms. Self‐reported depressive symptoms were reported to a greater extend in women compared to men. Our findings indicate that the Iranian populations living in both Tehran and Stockholm report depressive symptoms to an extent that merits concern. The findings indicate that Iranians living in Tehran and Iranians who have immigrated to Sweden require more attention regarding mental health care. Health care providers in both countries should be aware of the current state of mental health among Iranians in both Sweden and Iran.     

Anti-angiogenesis therapy in cancer: current challenges and future perspectives

It has been nearly 9years since the FDA (Food and Drug Administration) approved the first anti-angiogenic drug (bevacizumab) for treatment of metastatic colorectal cancer. Other angiogenic inhibitors have since been approved or are in different stages of clinical trials. However, continued clinical and preclinical investigations have identified major drawbacks associated with the application of this class of agents, including inherent/acquired resistance and induction of tumor invasiveness. In addition, lack of thoroughly validated predictive biomarkers has been one of the major hurdles to stratify cancer patients and to monitor tumor progression and response to the therapy. Investigations in clinic and preclinical models have provided some molecular and cellular mechanisms for the above challenges. This review aims to provide a concise update from recent findings.     

Overlapping gastroesophageal reflux disease and irritable bowel syndrome:Increased dysfunctional symptoms

AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome crit...     

Cervical transverse myelitis after chickenpox in an immunocompetent patient

Varicella-zoster viruses complications involving the CNS are estimated to occur rarely, transverse myelitis after Varicella-zoster virus in most patients is characterized by an abrupt onset of progressive weakness and sensory disturbance in the lower extremities , like other viruses. We describe the case of 17 year-old boy who experienced cervical transverse myelitis after chickenpox with inability to walk and with urinary retention. He was not treated with any medication but complete recovery has been occurred.     

Pregnancy outcome in patients with stage 1a endometrial adenocarcinoma,who conservatively treated with megestrol acetate

Objective  

The most effective treatment of well-differentiated endometrial carcinoma is surgery. The aim of this study is the evaluation of megestrol acetate on young patients with well-differentiated endometrial cancer who wish to preserve their fertility, with regard to the receptors.     

Refractoriness to antivascular endothelial growth factor treatment: role of myeloid cells

CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived suppressor cells, have been shown to contribute to tumor angiogenesis. Recently, we found that accumulation of CD11b+Gr1+ in tumors renders them refractory to angiogenic blockade by vascular endothelial growth factor (VEGF) antibodies. This effect was traced to a pathway of CD11b+Gr1+-mediated angiogenesis that is, at least in part, driven by the secreted protein Bv8, which is up-regulated by the important myeloid growth factor granulocyte colony-stimulating factor (G-CSF). Thus, G-CSF may promote tumor angiogenesis through a Bv8-dependent pathway that bypasses VEGF and renders tumors refractory to anti-VEGF therapy.     

Hydroa Vacciniforme with Eye Involvement: Report of Two Cases

We herein report two patients with hydroa vacciniforme and concomitant ophthalmic involvement, primarily in the form of keratoconjunctivitis leading to corneal opacity. Awareness of this occasional manifestation may help to prevent severe complications.