Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling.

BACKGROUND: In the past decades studies on anti-tumoral drugs inhibiting matrix metalloproteinase (MMPs) were disappointing. Recently, we demonstrated that mature endothelial cells (ECs) and endothelial colony forming cells (ECFCs) can switch between invasion modes to cope with challenging environments, performing the "amoeboid angiogenesis" in the absence of proteases activity. METHODS: We first set out to investigate by ELISA if the inhibitors of the main protease family involved in angiogenesis were differently expressed during breast cancer progression. We used Marimastat, a broad-spectrum MMP inhibitor, as a means of inducing amoeboid characteristics and studied VEGF role in amoeboid angiogenesis. Thus, we performed invasion and capillary morphogenesis assay, morphological, cell signaling and in vivo mouse studies. RESULTS: Our data showed that TIMP1, TIMP2, alpha2-antiplasmin, PAI-1 and cystatin increase in breast cancer serum of patients with primary cancer and lymph node positive compared to healthy women. In vitro results revealed that the most high-powered protease inhibitors able to induce amoeboid invasion of ECFCs were TIMP1, 2 and 3. Surprisingly, Marimastat promotes ECFC invasion and tubular formation in vitro and in vivo, inducing amoeboid characteristics. We observed that the combination of Marimastat plus VEGF doesn't boost neither cell invasion nor vessel formation capacity. Moreover, inhibition of VEGF activity with Bevacizumab in the presence of Marimastat confirmed that amoeboid angiogenesis is independent from the stimulus of the main vascular growth factor, VEGF. CONCLUSIONS: We underline the importance to consider the amoeboid mechanism of endothelial and cancer cell invasion, probably responsible for the failure of synthetic metalloproteinase inhibitors as cancer therapy and tumor resistance to VEGF-targeted therapies, to set-up new drugs to be used in cancer therapy.

Identification and Assessment of Risks in Biobanking: The Case of the Cancer Institute of Bari.

Although research biobanks are among the most promising tools to fight disease and improve public health, there are a range of risks biobanks may face that mainly need to be assessed in an attempt to be relieved. We conducted a strategic insurance review of an institutional cancer biobank with the aim of both identifying the insurable risks of our own Biobank and gathering useful evidence of primary exposure to insurable risks. In this practical scenario, risks have been outlined and categorized into inherent and residual risks, along with their possible impact on biobank maintenance. Results at the Biobank of the Cancer Institute of Bari showed evidence of potentially significant and intrinsic risk due to highly relevant threats, along with already implemented improvements that significantly reduce risks to a range of relative acceptability.

Diet, Probiotics and Physical Activity: The Right Allies for a Healthy Microbiota.

The intestinal microbiota, which has gained a foothold in the field of research, represents a significant factor for human health because of its ability to form relationships with the organism through the modulation of pathophysiological processes. Dysbiosis, which is caused by non-specific intestinal inflammation and leads to a condition of persistent low-grade inflammation, may be caused by poor eating habits and an unhealthy lifestyle, as well as psycho-physical stress and a sedentary lifestyle. Diet, prebiotics and probiotics, and moderate and aerobic exercise can, in order to increase well-being and reduce the chance of recurrence, all be deemed effective methods of improving gut-microbiota pretreatment or mitigating diseases or dysbiosis. This study shows the ways in which good living habits, correct nutrients, and constant aerobic activity in chronic and immune conditions, can modify gut microbiota and microbiome characteristics, as well as the relationship between intestinal function and human health.

Minimum biobanking requirements: issues in a comprehensive cancer center biobank.

Cancer biobanks, when located within a comprehensive cancer center, are characterized by management and organizational peculiarities mainly related to the multidisciplinary information available of such specialized centers and the continuous collection stream of quality-assessed biospecimens. The present study summarizes the main characteristics of comprehensive cancer center biobanks and, more in detail, procedures addressed in order to maintain full control over interlacement issues that occur at every level, from patient enrolment eligibility and consenting to dissemination and utilization of specimens and associated data. Dedicated personnel, appropriate storage facilities, as well as ethical, legal, and technical requirements are among the most relevant aspects strongly conditioning the quality of these structures. Because of its location and the need to be directly connected with clinical units, such as pathology, oncology, surgery, etc., ad hoc information technology tools are crucial to support all aspects of biorepository operations, including (but not limited to) patient enrolment and consent; biospecimen collection, processing, storage, and distribution; quality assurance and quality control; collection of patient data; validation documentation; and management reporting functions.