OncoGenex Pharmaceuticals (United States)

The present study highlights about alkali element modification of glucose molecules as a method to dissolve cancer cells. The central regulation of the mechanisms governing cell proliferation has little effect on cancer cells. Cancer cells are entirely independent of the central command and divide and proliferate on their own, making it challenging to activate their response mechanism. Precisely, this is the reason why they are at risk to the health of humans and/or any biological entities. Instead of trying to reconnect the central command of the growth control mechanism to cancer cells that are already out of the range, we present a method of using the cancer cell’s own irresponsive and uncontrolled growth mechanism to their disadvantage and destroy the cancer cells. We found that this is achievable in an atomic/molecular level study of the glucose molecule, which is the primary food source used for growth and energy generation by all cells in the body, including the cancer cells. Testimonials of the clinical trial of the supplement provide proof of dramatic recovery from the advanced stage of cancer in seven days. Finding the most effective number “Y” of the alkali element in the glucose molecule in such a way that the cancer cells cannot recognize the modification will be a very important scientific task to investigate and to perform further research to amplify the efficacy of the alkali-element-modified glucose molecule for cancer treatment.

5014 Background: GSTP1 inactivation is associated with CpG island hypermethylation in > 99% prostate cancers. Detection of circulating mGSTP1 DNA predicts response to DTX and overall survival (OS) in phase I/II mCRPC cohorts. This post hoc analysis of a phase III study aims to test the association between circulating mGSTP1 DNA levels and outcomes. Methods: The phase III SYNERGY study tested DTX +/- custirsen as 1st line chemotherapy in mCRPC (n = 1022) with no OS benefit in the experimental arm. Serum samples were taken at baseline (BL) and preC3 of DTX +/- custirsen from 600 patients (pts) enrolled on the SYNERGY study. mGSTP1levels in free DNA were measured using a sensitive methylation specific PCR assay and correlated with PSA response, time to PSA progression (TTP) and OS. Results: On interim analysis of 300 pts, serum mGSTP1 was detectable at BL in 80% and preC3 in 44%. Undetectable preC3 mGSTP1 correlated with a ≥30% fall in PSA within 3m of starting DTX (p < 0.001). Detectable BL and preC3 mGSTP1 predicted shorter TTP after DTX (BL; HR 1.6 95%CI 1.1-2.3; p = 0.01 and preC3 HR 2.2 95%CI 1.6-2.9; p < 0.001). Detectable mGSTP1 at both time points predicted shorter OS (BL; median OS 18.4 vs 33.1m, HR 2.4 95%CI 1.6-3.7; p < 0.001 and preC3; median OS 13.9 vs 29m, HR 2.7 95%CI 2.0-3.6; p < 0.001). In those with detectable BL mGSTP1, 50% had undetectable preC3 mGSTP1 predicting > 30% fall in PSA within 3m (p < 0.001), improved TTP (HR 0.40 95%CI 0.29-0.57; p < 0.001) and improved OS (25.2 vs 13.9 m HR 0.38 95%CI 0.28-0.51; p < 0.001). On multivariable analysis including Hb, Karnofsky PS, LDH, PSA and visceral metastases, detectable preC3 mGSTP1 independently predicted shorter TTP (HR 1.9 95%CI 1.4-2.6; p < 0.001). Detectable mGSTP1at both time points independently predicted OS (BL; HR1.8 95%CI 1.2-2.8; p = 0.006 and preC3; HR 2.2 95%CI 1.6-3.0; p < 0.001). Results from the full cohort of 600 pts will be available for presentation at the meeting. Conclusions: This study should validate circulating mGSTP1 DNA as a marker of therapeutic benefit and prognosis in men with mCRPC receiving DTX and could be utilized for clinical management.

The growing interest in philanthropy education in K–12 schools stems from concerns with the health of American democracy. This article analyzes the size and scope of philanthropy education at U.S. independent K–12 schools. Based on both a Web-based survey with 128 independent K–12 schools and telephone interviews with a purposive sample of teachers and program administrators, the article describes the variety of activities, educational methodologies, and learning goals associated with philanthropy education. It then develops a typology of philanthropy education at K–12 school that aims to clarify the terminology used in philanthropy education at K–12 schools. In so doing, this article assists teachers and program administrators in developing more effective programs and assessment tools in the field of philanthropy education. Subscribe to JNEL

TPS4588^ Background: Heat shock protein 27 (Hsp27) is over-expressed in many cancers including bladder, lung, prostate, and breast. Increased Hsp27 has been associated with inhibition of chemotherapy-induced apoptosis, increased tumor cytoprotection, and development of treatment resistance. OGX-427 is an antisense oligonucleotide designed to bind Hsp27 mRNA, inhibiting production of the Hsp27 protein. Inhibition of Hsp27 has been shown to increase apoptosis, inhibit tumor growth, and sensitize tumor cells to chemotherapy in a variety of malignancies, including urothelial cancer. Results of preclinical and phase 1 studies suggest that addition of OGX-427 to chemotherapy is well tolerated and may improve treatment efficacy. BOREALIS-2 is a randomized, multicenter, phase 2 study of OGX-427 in combination with docetaxel (DOC) vs. DOC alone in locally advanced/metastatic bladder cancer patients who received at least one line of prior platinum-based therapy. The primary objective is to evaluate overall survival. Secondary objectives include comparisons of safety and tolerability, disease response, and serum levels of Hsp27 and other pathway-related proteins. Associations between clinical outcomes, levels of Hsp27 and other proteins, and circulating tumor cells will be evaluated. Methods: Patients (N=200) are randomized in a 1:1 ratio following stratification (time from prior systemic chemotherapy; Bellmunt criteria). Up to 2 prior systemic therapies are allowed. Treatment-arm patients receive three loading doses of OGX-427 (600 mg) followed by up to ten 21-day treatment cycles (OGX-427 1000 mg on Days 1, 8, and 15 and DOC 75 mg/M2 IV on Day 1). Control-arm patients receive DOC 75 mg/M2 IV on Day 1 of each cycle. Treatment may continue until disease progression, unacceptable toxicity, completion of 10 cycles, or patient withdrawal. Patients who discontinue DOC due to toxicity after ≥2 cycles and do not have disease progression may receive maintenance therapy with OGX-427. One interim futility analysis will be performed. The trial will not be stopped early based on efficacy. Clinical trial information: NCT01780545.

We cloned and analyzed the murine cot proto‐oncogene and examined its tissue‐specific expression in fetal, newborn and adult mice. Genomic cot DNA consists of eight exons, spanning more than 25 kb, and all intron‐exon borders are well conserved as compared to the human homolog. Analysis of the full‐length cot cDNA revealed that it contained an open reading frame of 1,401 nucleotides, like human cot proto‐oncogene. The sequence identity between murine and human cot gene is 84.4% at the nucleotide level and 93.9% at the deduced amino acid level. On northern blot analysis of poly (A)+ RNA, the cot message was detected at 2.9 kb in size. Expression of the cot gene was observed in many tissues from fetal to adult mice, though the level of expression was low in all tissues examined.