The Women's Health Study (WENDY) was conducted to improve insights into women's health and health burden. It provides a unique, comprehensive data source that can be broadly utilised to understand gynaecological symptoms, diseases, and their relation to metabolic and overall health more deeply in a population-based setting. The study was conducted in Finland from May 2020 to October 2022.
View Article and Find Full Text PDFFor long it has been recognized that tumor necrosis factor alpha (TNFa) has anticancer characteristics, and its use as a cancer therapeutic was proposed already in the 1980s. However, its systemic toxicity has limited its usability. Oncolytic viruses, selectively cancer-killing viruses, have shown great potency, and one of their most useful aspects is their ability to produce high amounts of transgene products locally, resulting in high local versus systemic concentrations.
View Article and Find Full Text PDFIntroduction: The aim was to elucidate the costs and clinical results of sterilization.
Material And Methods: A retrospective analysis was carried out on sterilizations conducted at the Hyvinkää hospital in 2006 to 2007 by tubal ligation with clips and by microimplants.
Results: Total costs obtained for microimplant sterilization per patient were 1,146 Euros and for clip sterilization 1,712 Euros.
Oncolytic adenoviruses can be engineered for better tumor selectivity, gene delivery and be armed for imaging and concentrating radionuclides into tumors for synergistic oncolysis. We constructed Ad5/3-hTERT-hNIS where replication is controlled by hTERT-promoter. Ad5/3-hTERT-hNIS expresses hNIS for imaging of transgene expression and for treatment of infected tumors by radioiodine.
View Article and Find Full Text PDFPurpose: In the present study, we evaluated the combination of replication-deficient adenoviruses and radiotherapy in vitro. The purpose of the present study was to analyze the mechanism of radiation-mediated upregulation of adenoviral transgene expression.
Methods And Materials: Adenoviral transgene expression (luciferase or green fluorescent protein) was studied with and without radiation in three cell lines: breast cancer M4A4-LM3, prostate cancer PC-3MM2, and lung cancer LNM35/enhanced green fluorescent protein.
Patients with advanced solid tumors refractory to and progressing after conventional therapies were treated with three different regimens of low-dose cyclophosphamide (CP) in combination with oncolytic adenovirus. CP was given with oral metronomic dosing (50 mg/day, N = 21), intravenously (single 1,000 mg dose, N = 7) or both (N = 7). Virus was injected intratumorally.
View Article and Find Full Text PDFOncolytic adenoviruses are an emerging treatment option for advanced and refractory cancer. Such patients are often treated with corticosteroids to ameliorate tumor associated symptoms. Thus, it is important to evaluate whether safety is affected by immunosuppression possibly induced by corticosteroids.
View Article and Find Full Text PDFPurpose: Radiotherapy is widely used for treatment of many tumor types, but it can damage normal tissues. It has been proposed that cancer cells can be selectively sensitized to radiation by adenovirus replication or by using radiosensitizing transgenes. Adenoviral proteins E1B55K, E4orf3, and E4orf6 play a role in radiosensitization, by targeting the Mre11, Rad50, and NBS1 complex (MRN) and inhibiting DNA double-strand break (DSB) repair.
View Article and Find Full Text PDFAugmenting antitumor immunity is a promising way to enhance the potency of oncolytic adenoviral therapy. Granulocyte-macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific CD8(+) cytotoxic T-lymphocytes. Serotype 5 adenoviruses (Ad5) are commonly used in cancer gene therapy.
View Article and Find Full Text PDFPurpose: Twenty-one patients with cancer were treated with a single round of oncolytic adenovirus ICOVIR-7.
Experimental Design: ICOVIR-7 features an RGD-4C modification of the fiber HI-loop of serotype 5 adenovirus for enhanced entry into tumor cells. Tumor selectivity is mediated by an insulator, a modified E2F promoter, and a Rb-binding site deletion of E1A, whereas replication is optimized with E2F binding hairpins and a Kozak sequence.
Granulocyte macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific cytotoxic T-cells through antigen-presenting cells. Oncolytic tumor cell-killing can produce a potent costimulatory danger signal and release of tumor epitopes for antigen-presenting cell sampling. Therefore, an oncolytic adenovirus coding for GMCSF was engineered and shown to induce tumor-specific immunity in an immunocompetent syngeneic hamster model.
View Article and Find Full Text PDFPurpose: Oncolytic adenoviruses are promising tools for cancer therapy. Although several clinical reports have indicated both safety and promising antitumor capabilities for these viruses, there are only a few examples of complete tumor eradication. Thus, the antitumor efficacy of oncolytic adenoviruses needs to be improved.
View Article and Find Full Text PDFNew treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti-cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment.
View Article and Find Full Text PDFBackground: Rapid clearance of adenoviruses from blood by macrophage lineage cells of the liver and spleen, and binding to platelets, hinder their successful systemic use for cancer gene therapy. Vitamin K dependent coagulation factors are important mediators for the adenovirus liver tropism. Here we aim to determine the effects of coagulation factor, thrombocyte and liver macrophage (Kupffer cell) ablation on biodistribution of serotype 5 adenoviruses in mice with orthotopic breast tumors.
View Article and Find Full Text PDFDespite some advances, patients with advanced renal cell carcinoma (RCC) cannot usually be cured. Alteration of the natural tropism of adenoviruses may permit more specific gene transfer to target tissues. The aim of this study was to use novel targeting moieties for adenoviral gene therapy of RCC.
View Article and Find Full Text PDFRenal cancer is a common and deadly disease that lacks curative treatments when metastatic. Here, we have used oncolytic adenoviruses, a promising developmental approach whose safety has recently been validated in clinical trials. Although preliminary clinical efficacy data exist for selected tumor types, potency has generally been less than impressive.
View Article and Find Full Text PDFHormone refractory metastatic prostate cancer is a deadly disease that currently lacks curative treatments. Conditionally replicating adenoviruses (CRAds) are promising new agents against cancer due to their innate capability to cause oncolysis of tumor cells. Their antitumor effect is determined in part by their capacity for infecting cancer cells.
View Article and Find Full Text PDFWe carried out a prospective cohort study to determine whether the plasma levels of fibrinogen, plasminogen, factor VII and lipoprotein (a) are predictors of ischemic stroke and all cardiovascular disease (CVD) events. The FINRISK '92 Hemostasis Study included a random sample of 2372 participants, who were followed-up from winter 1992 to 31 December 2001. During the follow-up, 75 ischemic stroke and 145 coronary events occurred.
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