CPCs and ECM. A good mix for cardiac regeneration

ABSTRACT Despite several improvements in term of diagnosis and prevention, ischemic heart disease still represents one of the principal worldwide causes of death. Cardiac progenitor cells (CPCs) based therapy is considered a valid alternative to heart transplant, but several issues concerning the transplanted cells viability, retention and therapeutic effect need to be solved. Tissue engineering, mixing synthetic or natural polymers with injected cells, could represent the way through which overcomes shortages and set up an effective cardiac regenerative therapy. Nowadays, it is well known that cardiac extracellular matrix (ECM) provides structural and functional integrity, affects cardiac function, development and physiologic repair. In this optic, ECM and ECM-like materials represent functional and biocompatible tools with a great potential to serve as natural or nature-mimicking scaffolds in the field of regenerative medicine. The aim of the present work is to provide an overview on the state of the art and recent advantages on CPCs and scaffold-based therapy for heart regeneration

Urothelial bladder carcinoma metastasizing to the eye: a systematic review and case report

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta Analyses

Expression and localization of Phosphoinositide-specific Phospholipase C enzymes in polarized macrophages

The phenotypic and functional diversity of macrophages depends on differentiating programs being developed during the cells’ lives. Great interest was addressed to identify the signal transduction pathways acting in macrophage polarization, including the phosphoinositide (PI) system and related phospholipase C (PLC) family of enzymes. Enzymes belonging to the PLC family are strictly tissue specific and the expression panel, as well as the subcellular localization differs in quiescent cells compared to the pathological counterpart. We analyzed the expression of PLC enzymes in unpolarized (M0), M1 and M2 macrophages to list the isoforms expressed in the polarized macrophages and their subcellular localization. Our results confirmed that macrophages express a wide number of PLC isoforms. All PLC enzymes were detected within both M1 and M2 cells, but not in M0 cells. M0, as well as M1 and M2 cells own a specific panel of expression, different for both genes’ mRNA expression and intracellular localization of PLC enzymes. PLC enzymes might play a complex role in macrophages during inflammation and probably also during polarization

Wounds difficult to heal. An effective treatment strategy

OBJECTIVE: Treatment of wounds difficult to heal concerns 50% of the elderly population in Italy and is therefore a relevant social burden. The present study shows how the treatment with autologous leuco-platelets reduces the healing time of wounds improving the functional recovery. PATIENTS AND METHODS: Patients (n=100) with ulcers of the legs were divided in two groups: 1) 50 patients treated with conventional therapies; 2) 50 patients treated with autologous leuco-platelet concentrate (LPC) and hyaluronic acid (HIAFF, Hyalofill-F ® as a scaffold. RESULTS: After 2 months, a 49% reduction in wound area was observed in the second group and in about 65% wound reduction was achieved in 15 days (4 LPC dressings). In contrast, patients treated by conventional therapies, showed a longer healing time and a greater percentage of failures. Morphometric analysis of biopsy samples obtained from the edge as well as from the bottom of the lesions obtained from the LPC group, detected an abundant presence of neoformed capillaries, characterized by a cubic, "reactive endothelium", close to the site of LPC infiltration. CONCLUSIONS: These results suggest that healing was promoted not only by limiting bacterial infections but also by the release of chemotactic and proangiogenic factors from leukocytes and platelets, improving the neoformation of capillaries.Abstract: Objective: Treatment of wounds difficult to heal concerns 50% of the elderly population in Italy and is therefore a relevant social burden. The present study shows how the treatment with autologous leuco-platelets reduces the healing time of wounds improving the functional recovery. Patients and Methods: Patients (n=100) with ulcers of the legs were divided in two groups: 1) 50 patients treated with conventional therapies; 2) 50 patients treated with autologous leuco-platelet concentrate (LPC) and hyaluronic acid (HIAFF, Hyalofill-F®) as a scaffold. Results: After 2 months, a 49% reduction in wound area was observed in the second group and in about 65% wound reduction was achieved in 15 days (4 LPC dressings). In contrast, patients treated by conventional therapies, showed a longer healing time and a greater percentage of failures. Morphometric analysis of biopsy samples obtained from the edge as well as from the bottom of the lesions obtained from the LPC group, detected an abundant presence of neoformed capillaries, characterized by a cubic, "reactive endothelium", close to the site of LPC infiltration. Conclusions: These results suggest that healing was promoted not only by limiting bacterial infections but also by the release of chemotactic and proangiogenic factors from leukocytes and platelets, improving the neoformation of capillaries

JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer

Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear

Enhance PARPi Application beyond BRCA-Mutant Breast Cancer (BC): Facts Are Facts

Breast cancer (BC) represents one of the three most common neoplasia and the principal worldwide leading cause of death among women [...

CTCs and the metastatic process: the complexity of malignancy.

Despite improvements achieved in terms of early detection and therapeutic approach, metastatic breast cancer remains one of the principal worldwide causes of death. In recent years, due to the heterogeneous response of each patient to chemotherapy, clinical research highlights the needed of a personalized approach. Circulating tumor cells represent a promising tool for this purpose. Unfortunately, even if their correlation with severity, outcome and metastatic nature of the tumor it has been established, several issues, mainly concerning their characterization and isolation, need to be solved. In this review, latest knowledges on circulating tumor cells and metastatic process in breast cancer were analyzed, aiming to understand their clinical utility and validity for a prospective therapeutic scenario

Circulating tumor cells and the metastatic process: the complexity of malignancy

Despite improvements achieved in terms of early detection and therapeutic approach, metastatic breast cancer remains one of the principal worldwide causes of death. In recent years, due to the heterogeneous response of each patient to chemotherapy, clinical research highlights the need of a personalized approach. Circulating tumor cells (CTCs) represents a promising tool for this purpose. Unfortunately, even if their correlation with severity, outcome and metastatic nature of the tumor has been established, several issues, mainly concerning their characterization and isolation, need to be solved. In this review, latest knowledge on CTCs and metastatic process in breast cancer were analyzed, aiming to understand their clinical utility and validity for a prospective therapeutic scenario

Expression of phosphoinositide-specific phospholipase C isoforms in human umbilical vein endothelial cells

Aims The signalling system of phosphoinositides (PIs) is involved in a number of cell and tissue functions including membrane trafficking, ion channel activity, cell cycle, apoptosis, differentiation and cell and tissue polarity. Recently, a role in cell migration was hypothesised for PI and related molecules including the phosphoinositide-specific phospholipases C (PI-PLCs), main players in PI signalling. The expression of PI-PLCs is tissue-specific and evidence suggests that it varies under different conditions such as tumour progression or cell activation. In order to obtain a complete picture, the expression of all PI-PLC isoforms was analysed in human endothelial cells (EC). Methods Using molecular biology methods (RT-PCR), the expression of PI-PLC isoforms was analysed in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for human EC. Results All the PI-PLC isoforms except PI-PLC beta 1, PI-PLC epsilon and PI-PLC zeta were expressed in HUVEC. Conclusions The growing interest in the complex cascade of events occurring in angiogenesis will provide useful insights for therapeutic strategies. The expression of PI-PLC isoforms in HUVEC is a useful tool for further studies directed to understanding their role in angiogenesis. However, although HUVEC represent a widely used experimental model for human macrovascular EC, limitations remain in that they cannot fully represent the metabolic properties and interactions of the EC distributed in the entire organism