Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose. Ten patients with breast and ovary cancers that progressed after Elenagen were then treated with conventional chemotherapy. Adverse events (AE) were of Grade 1; no severe AE were observed. Cumulatively twelve patients (44%) with breast, ovary, lung, renal cancer and melanoma achieved stable disease for at least 8 wks, with 4 of them (15%) had tumor control for more than 24 wks, with a maximum of 32 wks. The patients with breast and ovary cancers achieved additional tumor stabilization for 12-28 wks when treated with chemotherapy following Elenagen treatment. Therefore, Elenagen demonstrated good safety profile and antitumor activity in advanced solid tumors. Especially encouraging is its ability to restore tumor sensitivity to chemotherapy.
Background: Ethnic diversity of the population in the region of Siberia suggests the existence of different germline mutations in the BRCA1/2 genes associated with breast and ovarian cancer in different ethnic populations, but spectrum of these mutations has not been studied. Objective: Our aim was to evaluate the frequency of the most common mutations BRCA1 / 2 (BRCA1 5382insC, BRCA1 185delAG, BRCA1 4153delAG, BRCA1 T300G, BRCA2 6174delT) in women diagnosed with breast cancer among indigenous people and newcomers living in Siberia. Methods: We tested 1281 genomic DNA samples for the presence of BRCA1 5382insC mutation in patients diagnosed with breast cancer considering no family history. 72 patients having hereditary cancer signs were tested for the mutations BRCA1 185delAG, BRCA1 4153delAG, BRCA1 T300G, BRCA2 6174delT. Results: Out of 765 patients of Slavic ethnic group, 27 women (3.5%) were carriers of allele BRCA1 5382insC. The frequencies of mutations in patients with signs of hereditary cancer were: 8.3% in group of young patients (under 40 years), 20.0% in patients with bilateral cancer and 5.7% in patients with family history of breast or ovarian cancers. We tested 516 BC patients residing on the territory of the Buryat-Aginsky district, Republics of Tyva and Altai. Out of them, there were 197 patients among the indigenous population (buryats, tuvinians, altaians), and 319 patients among newcomers (Slavic ethnics). Mutations BRCA1 5382insC were detected only in women from Slavic ethnic groups. The frequency of BRCA1 5382insC mutation was 6% in the group where family history was excluded and 14% in the group of patients with characteristics of family cancer. Allele BRCA1 5382insC was not found in indigenous breast cancer patients, although 59 patients had signs of hereditary cancer. In women from Slavic ethnic group, the BRCA1 185delAG, BRCA1 4153delAG and BRCA1 T300G mutations were detected in 9.1% of cases and were not found in patients among the indigenous population. Conclusion: studies of mutations in the BRCA1 gene in breast cancer patients from Siberia confirmed data on the high frequency of «founder mutation» BRCA1 5382insC in Slavic population and indicate the advisability of further studies to identify the genes responsible for the occurrence of hereditary breast cancer in the indigenous population.
Background. Perioperative myocardial ischemia often complicates extracardiac surgery. The problems of its prediction, diagnostics, treatment and prevention are not solved. Frequency, structure and clinical features of cardiac ischemic complications of surgical treatment of lung cancer are not well understood.The aim of the study was to investigate the frequency of postoperative myocardial infarction and myocardial ischemia in the surgical treatment of patients with non-small cell lung cancer.Methods. The frequency (%) of myocardial infarction (MI) with and without ST segment elevation of electrocardiogram, acute myocardial ischemia in a complete sample of cancer patients (n = 2051) who underwent treatment for non-small cell lung cancer for the last 10 years was calculated. By comparing the relative indicators and calculating the Odds Ratio (OR), we studied the relationship between the cardiac ischemic events with age, type of surgery, prevalence and localization of the tumour. The clinical manifestations and pathomorphology of postoperative myocardial infarction were analysed.Results. Cardiac ischemic complications of thoracotomy for lung cancer occurred in 2.73 % (95% CI 1.98–3.48) cases. Myocardial infarction with ST segment elevation was recorded in 1.07 % (95% CI 0.58–1.57) patients, MI without ST segment elevation – in 0.54 % (95% CI 0.17–0.9), myocardial ischemia – in 1.12 % (95% CI 0.62–1.63). An increase in the frequency of ischemic events after pneumonectomy was observed compared with lobectomy (OR 6.5, 95% CI 3.5–12.2) and after right-sided pneumonectomy compared with left-sided one (OR 3.2, 95% CI 1.6–6.3), and also the age over 70. Hospital mortality from MI was 39.3 %. According to autopsies of patients who died of МI, coronary atherothrombosis was detected in 2 of 22 cases.Conclusion. In the surgical treatment of non-small cell lung cancer, cardiac ischemic events develop in 2.73 % of patients. The greatest risk is associated with right-sided pneumonectomy.
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