First study of the safety and tolerability of Allvec-1, a gene therapy vector, in patients with advanced stage IV malignant solid tumors

Background: Gene therapy relies on the delivery of foreign DNA into cells. More than 50% of all reported clinical trials for gene therapy are for cancer

Objectives: To test the tolerability, safety, and recommended phase II dose of Allvec-1, a highly selective gene therapy vector, after systemic administration in patients with advanced stage IV solid tumor malignancies

Patients and Methods: A phase I trial evaluated escalating doses of Allvec-1, administered 3 times weekly for 8 weeks in 6 patients with gastric, breast, esophageal, non-small cell lung cancer [NSCLC], and leiomyosarcoma. Clinical lab parameters, blood pressure, pulse and patients' own-reported adverse events were used for evaluation of safety. The maximum dose was set based on the first sign of any minor side effect to be likely related to Allvec-1. Tumor imaging techniques were applied before and after Allvec-1 treatment for any tumor response. No further concomitant anti-tumor treatment was admitted during the study period

Results: Six patients [median age, 50.5 years [range 23-66], they were heavily pretreated; received Allvec-1 starting at a dose of 1.25 × 10[10] and increasing to the final dose of 2 × 10[11] thrice weekly. During the study period 3 patients have received 24, one patient 21, one patient 14, and one patient 13 intravenous [I.V] injections, respectively. Treatment-related adverse events were nausea [1 out of 6] and increase of body temperature [38 degree C, 2 out of 6]. These side effects were minor and lasted only up to 30 minutes, and disappeared after repeated dosing. The increase of body temperature occurred 24 to 48 hours after the treatments and was observed only during the second week. No other side effects were reported. All clinical lab and vital functions remained unaffected. An increase of body weight and an improvement of general condition could be observed in 4 out of 6 patients. One of these patients showed stable disease until the end of 4 weeks surveillance period. A partial response was seen in 1 out of 6 patients. Four patients died within one month after termination of the treatment due to the progressive dieses

Conclusions: Allvec-1, as the first gene therapy vector for systemic administration, was tolerated without any side effects. Dose-limiting toxicities were not observed in this study. Therefore, higher doses can be recommended in phase II trials. Despite extensive prior treatment and final stage of all patients a partial response and stable disease could be reached during the treatment period. It could be expected that a treatment beyond 8 weeks, even in those terminally ill patients, might increase the life expectancy without any side-effects. Therefore, additional clinical trials are well warranted in defining the role of Allvec-1 in treatment of cancer

Effects of soy on metabolic biomarkers of cardiovascular disease in elderly women with metabolic syndrome

This study ascertained the effects of soy, in the forms of textured soy protein [TSP] and soy nuts, on lipid profiles, apolipoproteins, inflammatory and prothrombotic markers, and blood pressure in elderly women diagnosed with metabolic syndrome [MetS]. This was a 12-week parallel, randomized, controlled trial conducted in rural health centers of Babol, Iran. Participants were 75 women, ages 60-70 years, who were diagnosed with MetS. Subjects were randomized to one of the following 3 groups: i] soy nut [35g/d], ii] TSP [35g/d], and iii] control. Blood biochemical markers measured at baseline and at the end of the study included: triglycerides [TG], cholesterol, HDL-C, LDL-C, VLDL-C, ApoB100, ApoAI, C-reactive protein [CRP], and fibrinogen. Soy nuts significantly improved LDL-C, VLDL-C, and ApoB100levels [P < 0.05], while fewer, significant improvements were observed in these variables in the TSP group compared to mean changes from baseline [P < 0.001]. Similar results were found for ApoAI in the treatment groups [P < 0.01]. Serum total cholesterol [TC] decreased significantly in the treatment groups compared with the control group [P < 0.005]. Differences from the control group in terms of TG, HDL-C, fibrinogen, CRP, and blood pressure were not significant. Both forms of soy improved lipid profiles. The group that consumed soy nuts had greater improvement than the TSP group. Therefore, moderate daily intake of soy may be a safe, inexpensive, and practical method to improve the risk of cardiovascular disease [CVD] and reduce the need for medical treatment

Effects of soy on metabolic biomarkers of cardiovascular disease in elderly women with the metabolic syndrome

To ascertain the effects of soy [in the forms of Textured Soy Protein [TSP] and soy-nut] on lipid profiles, apolipoproteins, inflammatory and prothrombotic markers and blood pressure in elderly women with the metabolic syndrome. The study is a 12-week parallel randomized controlled trial that was conducted in rural health centres of Babol, Iran. The participants were 75 women 60-70 years old with the metabolic syndrome who were randomized to one of the three groups of soy-nut [35g/d], TSP [35g/d] and control. Blood pressure and blood biochemical markers were measured at baseline and at the end of the study including, triglyceride, cholesterol, HDL-C, LDL-C, VLDL-C, ApoB100, ApoAI, CRP and fibrinogen. The soy-nut improved significantly LDL-C, VLDL-C and Apo B100 [P<0.05] while fewer improvements but significant were observed in these variables in the TSP group only when compared with the mean changes from the baseline [P<0.001]. Similar result was found for Apo AI in the treatment groups [P<0.01]. Serum total cholesterol decreased significantly in the treatment groups compared with control group [P<0.005]. The differences from control for triglyceride, HDL-C, fibrinogen, CRP and blood pressure were not significant. Both forms of soy while improved lipids profiles the soy-nut contribution was more to this improvement than the TSP. Therefore, moderate daily intake of soy may be a safe, cheap and practical method to improve cardiovascular disease risk and also reduce the need for medical treatment

[Measurement of serum and 24-h urinary glucose amino glycans as an diagnostic marker in early hypertention]

Glucose Amino Glycans [GAG] are unbranched polysacharides, major components of the basement membrane and play a key role in their molecular organization and function, also have an important role in the pathogenesis of some diseases such as hypertension. Hypertention is probably the most important health problem in several countries. But there is not yet a reliable indicator for early diagnosis of hypertension. The goal of this study was the measurement of serum and 24-h urinary GAG as an exact and early diagnostic marker. In this case - control study, 24-h urine and serum samples collected from the 53 patients and 38 persons as matched control normotensive group. Then amount of GAG was measured with spectrophotometery method. Our findings showed that there is a direct relation between 24-h urinary GAG excretion and systolic blood pressure and it increases with increase of systolic blood pressure. Also amount of serum GAG increases in hypertensive patients in comparison with control group This study showed that the concentration of GAG in sera and 24-h of urine samples increase in systolic hypertention

Investigation of the effect of ginger on the lipid levels. A double blind controlled clinical trial

To study the effect of fine powder of ginger on lipid level in volunteer patients. This is a double blind controlled clinical trial study in 2 cardiac clinics Cardiac Disease Clinic, Babol, north of Iran, between April to May 2004. We randomly divided the patients with hyperlipidemia into 2 groups, treatment group [receiving ginger capsules 3 g/day in 3 divided doses] and placebo group [lactose capsule 3 g/day in 3 divided doses] for 45 days. All subjects with diabetes mellitus, hypothyroidism, nephrotic syndrome, and alcohol drinking, pregnancy and peptic ulcer were excluded. Lipid concentrations profile before and after treatment was measured by enzymatic assay. Forty-five patients in the treatment group and 40 patients in placebo group participated in this study. There was a significant reduce in triglyceride, cholesterol, low density lipoprotein [LDL], very low density lipoprotein [VLDL], levels of before and after study separately in each group [p<0.05]. Mean changes in triglyceride and cholesterol levels of ginger group were significantly higher than placebo group [p<0.05]. Mean reduction in LDL level and increase in high density lipoprotein level of ginger group were higher than the placebo group, but in VLDL level of placebo was higher than ginger [p>0.05]. The results show that ginger has a significant lipid lowering effect compared to placebo

Changing patterns of cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Babol, Iran

To investigate a 10-year trend of major cardiovascular risk factors in patients with acute myocardial infarction [AMI]. A retrospective study Babol Shahid Beheshti Hospital, Babol, Iran A total of 1236 consecutive patients with diagnosis of AMI. Major cardiovascular risk factors including history of hypertension, diabetes mellitus, mean of diastolic blood pressure measure ments, cholesterol and triglyceride level on the third day of hospitalization, age and gender were extracted from hospital records. The mean age [ +/- SD] of patients was 60.6 [ +/- 11.2] years and its trend was not significant during the 10-year period. Overall, 62% patients were male and 32% had history of hypertension and their trends were not statistically significant. Roughly, 24% of patients had diabetes mellitus and 32% had a history of smoking; the trend of these two risk factors tended to decrease over 10 years. There was a significant trend toward increasing diastolic blood pressure level at hospitalization [p < 0.0001]. The mean [ +/- SD] of cholesterol was 217 [64] mg/dl and the mean [ +/- SD] of triglyceride was 147 [97] mg/dl. Their trend was not statistically significant. Amultidimensional intervention program is necessary for prevention of cardiovascular risk factors. There is a need to promote health-related educational programs and to control the nutritional behavior and hypertension in order to cope with changing life styles