Mandatory role of endoplasmic reticulum and its pentose phosphate shunt in the myocardial defense mechanisms against the redox stress induced by anthracyclines.

Anthracyclines' cardiotoxicity involves an accelerated generation of reactive oxygen species. This oxidative damage has been found to accelerate the expression of hexose-6P-dehydrogenase (H6PD), that channels glucose-6-phosphate (G6P) through the pentose phosphate pathway (PPP) confined within the endoplasmic/sarcoplasmic reticulum (SR). To verify the role of SR-PPP in the defense mechanisms activated by doxorubicin (DXR) in cardiomyocytes, we tested the effect of this drug in H6PD knockout mice (H6PD).

Therapeutic efficacy of proton transport inhibitors alone or in combination with cisplatin in triple negative and hormone sensitive breast cancer models.

Triple negative breast cancers (TNBCs) are very aggressive and have a poor prognosis due to lack of efficacious therapies. The only effective treatment is chemotherapy that however is frequently hindered by the occurrence of drug resistance. We approached this problem in vitro and in vivo on a triple negative and a hormone sensitive breast cancer cell lines: 4T1 and TS/A.

Mechanisms underlying the predictive power of high skeletal muscle uptake of FDG in amyotrophic lateral sclerosis.

Background: We recently reported that enhanced [18F]-fluorodeoxyglucose (FDG) uptake in skeletal muscles predicts disease aggressiveness in patients with amyotrophic lateral sclerosis (ALS). The present experimental study aimed to assess whether this predictive potential reflects the link between FDG uptake and redox stress that has been previously reported in different tissues and disease models.

Methods: The study included 15 SOD1 mice (as experimental ALS model) and 15 wildtype mice (around 120 days old).

The Elusive Link Between Cancer FDG Uptake and Glycolytic Flux Explains the Preserved Diagnostic Accuracy of PET/CT in Diabetes.

This study aims to verify in experimental models of hyperglycemia induced by streptozotocin (STZ-DM) to what degree the high competition between unlabeled glucose and metformin (MET) treatment might affect the accuracy of cancer FDG imaging. The study included 36 "control" and 36 "STZ-DM" Balb/c mice, undergoing intraperitoneal injection of saline or streptozotocin, respectively. Two-weeks later, mice were subcutaneously implanted with breast (4 T1) or colon (CT26) cancer cells and subdivided in three subgroups for treatment with water or with MET at 10 or 750 mg/Kg/day.

Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy.

Observational/retrospective studies indicate that prostaglandin-endoperoxide synthase-2 (PTGS2) inhibitors could positively affect colorectal cancer (CRC) patients' survival after diagnosis. To obtain an acceptable cost/benefit balance, the inclusion of PTGS2 inhibitors in the adjuvant setting needs a selective criterion. We quantified the 72 kDa, CRC-associated, glycosylated form of PTGS2 in 100 frozen CRC specimens and evaluated PTGS2 localization by IHC in the same tumors, scoring tumor epithelial-derived and stroma-derived fractions.

Impact of CXCL1 overexpression on growth and invasion of prostate cancer cell.

Background: The role of CXCL1 in prostate cancer (PCa) progression has been poorly investigated. A limitation of previous studies is linked to the use of human PCa cell lines PC3 and DU145, producing CXCL8 at levels strongly exceeding CXCL1 levels. Moreover, in mouse models the sharing of CXCR2 receptor by both ligands makes the phenotype induced by CXCL8 and CXCL1 almost indistinguishable.

Celecoxib induces proliferation and Amphiregulin production in colon subepithelial myofibroblasts, activating erk1-2 signaling in synergy with EGFR.

The COX-2 inhibitor Celecoxib, tested in phase III trials for the prevention of sporadic colon adenomas, reduced the appearance of new adenomas, but was unable to affect the incidence of colon cancer. Moreover the 5years follow-up showed that patients discontinuing Celecoxib treatment had an increased incidence of adenomas as compared to the placebo arm. In the APC(min/+) mouse model short term treatment with Celecoxib reduced gut adenomas, but a prolonged administration of the drug induced fibroblast activation and intestinal fibrosis with a final tumor burden.

The AKT/NF-κB inhibitor xanthohumol is a potent anti-lymphocytic leukemia drug overcoming chemoresistance and cell infiltration.

Although the vast majority of patients with acute lymphocytic leukemia (ALL) attain remission with modern therapies, relapsed leukemia will continue to be a common malignancy both in childhood and in adults, until new treatments are available. Therapeutic options for advanced B-cell acute lymphocytic leukemia are still limited and acquired drug resistance and extramedullary tissue infiltration are two major obstacles during treatment. The prenylflavonoid xanthohumol (XN) has shown in vitro and in vivo therapeutic potential against a range of tumors.

Amniotic liquid derived stem cells as reservoir of secreted angiogenic factors capable of stimulating neo-arteriogenesis in an ischemic model.

Most urgent health problems are related to a blood vessel formation failure. The use of stem cells from different sources or species for both in vitro and in vivo engineering of endothelium does not necessarily imply their direct commitment towards a vascular phenotype. In the present study, we used human amniotic fluid stem cells (AFSC) to evoke a strong angiogenic response in murine recipients, in terms of host guided-regeneration of new vessels, and we demonstrated that the AFSC secretome is responsible for the vascularising properties of these cells.

Unsaturated fatty acids promote hepatoma proliferation and progression through downregulation of the tumor suppressor PTEN.

Background/aims: The impact of dietary fatty acids on the development of cancers is highly controversial. We recently demonstrated that unsaturated fatty acids trigger the downregulation of the tumor suppressor PTEN through an mTOR/NF-kappaB-dependent mechanism in hepatocytes. In this study, we investigated whether unsaturated fatty acids promote hepatoma progression by downregulating PTEN expression.

Marine sponge-derived polymeric alkylpyridinium salts as a novel tumor chemotherapeutic targeting the cholinergic system in lung tumors.

Previous studies have shown that the cholinergic system plays a pivotal rule in small cell lung cancer (SCLC) cell growth through an autocrine loop that activates the nicotinic cholinergic receptor, which together with the activation of this receptor by nicotine links SCLC evolution with tobacco use. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and is also linked to tobacco use. Here we describe the presence of molecules of the cholinergic system in NSCLC samples and cell lines and investigate the implications of the cholinergic system in cell growth regulation.

Kaposi's sarcoma and human chorionic gonadotropin: mechanisms, moieties and mysteries.

Kaposi's Sarcoma (KS) is a highly angiogenic neoplasm associated with infection by the human gamma-herpesvirus, HHV-8 or Kaposi's sarcoma herpes virus (KSHV). When in 1872 the Hungarian scientist Moritz Kaposi described the sarcoma, which was later named after him, he was dealing with a rare dermatologic disease. Today, KS is a more common pathology due to its high incidence in AIDS, in immuno-suppressed transplantation patients and, in its endemic form, in Africa.