Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.
Bone tissue engineering (BTE) uses principles from different fields, such as medicine, biochemistry and engineering, in order to restore or improve damaged tissue. Topographic changes of Poly-caprolactone scaffolds (PCL) have been previously induced by exposure of the polymer to various concentrations of NaOH for different periods of time. However, lack of consistency between the treatment conditions used by different research groups has led to inconsistent results, with no clear conclusion arising regarding the benefits of these treatments. The aim of this study was to evaluate how different treatments (time-concentration) with NaOH could affect its biocompatibility for bone marrow stromal cells (BMSC) and its cytotoxicity towards RAW 264.7 macrophages of a PCL scaffold. We also analyzed the physicochemical and mechanical properties of the PCL films after different treatment. We have shown that treatment with for 2 hours with NaOH produced changes that affected the hydrophobicity and biocompatibility of the scaffold by increasing the proliferation and ALP activity in cells grown on them. Beside, 24 hours of treatment with NaOH produced significant decreased in mechanical properties resulting in a scaffold highly fragile and low biocompatibility compared to PCL. Therefore, treatment for 2 hours with NaOH can be used to increase the biocompatibility of PCL scaffolds.
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