Diastereo- and enantioselective copper-catalyzed intramolecular carboamination of alkenes for the synthesis of hexahydro-1H-benz[f]indoles.

A new method for the enantioselective synthesis of hexahydro-1H-benz[f]indoles is described. This copper-catalyzed enantioselective intramolecular alkene carboamination process can install vicinal tertiary and quaternary carbon stereocenters with high levels of diastereo- and enantioselectivity. The C-C bond-forming component of the reaction constitutes a C-H functionalization and no electronic activation of the aryl ring that undergoes addition is required. A known 5-HT(1A) receptor antagonist was synthesized efficiently using this method.

Malignant lymphoma in Al-Qassim, Saudi Arabia, reclassified according to the WHO classification.

OBJECTIVE: To determine the frequency of various types of malignant lymphoma (ML) in the Al-Qassim region of Kingdom of Saudi Arabia (KSA) according to recently introduced the WHO classification. METHODS: For this retrospective analysis, material was available in 385 out of 519 cases diagnosed as ML from 1988-2007. Morphological assessment was followed by immunohistochemistry using a panel of antibodies. The study was conducted at Prince Faisal Oncology Centre (PFOC) of King Fahad Specialist Hospital (KFSH), Buraidah, Al-Qassim, KSA. RESULTS: Out of 385 cases reviewed, 251 (65.2%) had non-Hodgkin lymphoma (NHL) and 117 (30.4%) had Hodgkin lymphoma (HL). Male preponderance (male to female ratio 1.6:1) and a wide age range was observed (6 months to 103 years). B cell neoplasms were the most common NHL seen (81.6%) and diffuse large B cell lymphoma (DLBCL) was the most frequent type of NHL encountered (50.1%). Indolent lymphomas like follicular lymphoma (FL) and small lymphocytic lymphoma (SLL) were rather uncommon (13.2%). T cell lymphoma comprised 18.3% of the NHL. The most common type of HL was nodular sclerosis classical Hodgkin lymphoma (NSCHL) (68.3%). CONCLUSION: In Al-Qassim region of KSA, NHL is the most common ML seen and DLBCL the most common type. Unlike other parts of KSA and Middle East, NSCHL is the most common type of HL encountered.

In vitro and in vivo anticancer effects of the novel vitamin E ether analogue RRR-alpha-tocopheryloxybutyl sulfonic acid in prostate cancer.

PURPOSE: Among derivatives of alpha-vitamin E, alpha-vitamin E succinate (VES), has attracted much attention due to its potent anti-prostate cancer activity in vitro and in vivo. However, the in vivo antitumor activity of VES might be compromised if administrated orally due to the VES hydrolysis by esterases in the gastrointestinal tract. EXPERIMENTAL DESIGN: New nonhydrolyzable VES ether analogues were synthesized and their growth inhibition was screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide growth assay. Among them, RRR-alpha-tocopheryloxybutyl sulfonic acid (VEBSA) was further characterized by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling apoptosis assay, soft agar assay, and in vivo tumor formation. RESULTS: VEBSA has potent antitumor ability, albeit to a lesser extent than VES, in in vitro cultured prostate cancer LNCaP and PC3 cells. Like VES, VEBSA induced apoptosis, repressed androgen receptor protein expression, and enhanced vitamin D receptor expression, suggesting that VEBSA can go through mechanisms similar to those used by VES to inhibit the growth of prostate cancer cells in vitro. However, 6 weeks of oral consumption of VEBSA, but not of VES, reduced the tumor burden in the xenografted prostate tumors in nude mice. Furthermore, oral intake of VEBSA for 20 weeks inhibited prostate tumor growth and progression more efficiently compared with VES in the prostate cancer tumor model of TRAMP mice. CONCLUSION: Oral consumption of VEBSA allows a greater anticancer activity compared with VES. Chemoprevention prefers the oral consumption of agents; the advantage of VEBSA over VES to be administrated orally will allow VEBSA to serve as an agent for both preventive and therapeutic purposes for prostate cancer.

The Prognostic Value of E-cadherin Expression in Breast Cancer.

BACKGROUND: Breast cancer continues to be a major cause of morbidity and mortality throughout the world. The behavior of breast cancer varies widely. Several parameters have been investigated to predict the prognosis in breast cancer. But still there is no single parameter that can predict prognosis in an individual patient. Among the novel prognostic markers is E-cadherin; a calcium-dependent epithelial cell adhesion molecule. Its loss has been associated with metastases, thereby providing evidence for its role as an invasion suppressor. The objective of the present study was to assess the prognostic value of E-cadherin expression in breast cancer cases, and its correlations with the other studied prognostic parameters. METHODS: The study comprised 54 breast cancer patients admitted at King Fahd Specialist Hospital, Qassim during the period 2001-2006. The median tumor size was 3cms. Fifty cases (92.6%) had invasive ductal carcinoma, four cases had lobular carcinomas, and most were grade II (82%), stage II (48%), and the majority of cases had positive axillary lymph nodes (70.3%). Representative sections from formalin-fixed paraffin embedded tissue blocks were taken from the 54 cases of breast cancer, and were stained for E-cadherin expression by immunohistochemical technique (monoclonal E-cadherin (NCL-E-cad), Novocastra). All the lobular carcinoma cases were negative for membranous expression of E-cadherin while 72% of invasive ductal carcinomas were positive for the marker. RESULTS: A significant correlation was found between strong E-cadherin expression and node negative cases. Node negative cases were found to be an independent predictor of strong E-cadherin expression while node positive cases predicted negative expression of E-cadherin (P = 0 .026). Also loss of E-cadherin was noted in advanced stages of breast cancer supporting the view that loss of E-cadherin expression is a marker of aggressiveness. However, there was no correlation between the E-cadherin and other prognostic parameters as tumor size, tumor grade, ER, PR, and HER-2 expression. CONCLUSION: A significant correlation was found between strong E-cadherin expression and node negative cases.