Sensitizing cancer cells to immune checkpoint inhibitors by microbiota-mediated upregulation of HLA class I.

Recent data have shown that gut microbiota has a major impact on the clinical response to immune checkpoint inhibitors (ICIs) in the context of solid tumors. ICI-based therapy acts by unlocking cognate cytotoxic T lymphocyte (CTL) effector responses, and increased sensitivity to ICIs is due to an enhancement of patients' tumor antigen (TA)-specific CTL responses. Cancer clearance by TA-specific CTL requires expression of relevant TAs on cancer cells' HLA class I molecules, and reduced HLA class I expression is a common mechanism used by cancer cells to evade the immune system.

A Phase 2, Single-Arm, Open-Label Clinical Trial on Adjuvant Peptide-Based Vaccination in Dogs with Aggressive Hemangiosarcoma Undergoing Surgery and Chemotherapy.

To test the antitumor effect and safety of peptide-based anticancer vaccination in dogs with hemangiosarcoma undergoing the standard of care (SOC; surgery and doxorubicin), canine hemangiosarcoma cells were infected with Ty21a to release immunogenic endoplasmic reticulum stress-related peptides into the extracellular milieu via CX43 hemichannels opening. The infected tumor cell secretome constituted the vaccine. Following the SOC, dogs with biologically aggressive hemangiosarcoma were vaccinated a total of five times, once every 3 weeks, and were followed up with serial imaging.

A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy.

Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine.

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides.

Efforts to overcome resistance to immune checkpoint blockade therapy have focused on vaccination strategies using neoepitopes, although they cannot be applied on a large scale due to the "private" nature of cancer mutations. Here, we show that infection of tumor cells with Salmonella induces the opening of membrane hemichannels and the extracellular release of proteasome-generated peptides by the exacerbation of endoplasmic reticulum (ER) stress. Peptides released by cancer cells foster an antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering from osteosarcoma.

The Rise of the Stop the Bleed Campaign in Italy.

Background: The B-Con Basic 1.0 protocol is a medical training designed to teach how to control massive external haemorrhages in emergency conditions. Spread throughout the United States since 2013, thanks to the Stop the Bleed campaign, it has seen a progressive international spread during 2016-2018.

Association between lupus anticoagulant and epilepsy.

Lupus anticoagulant associated with thrombocytopenia, thrombosis or recurrent abortions was diagnosed in 2 epileptic patients chronically treated with anticonvulsant drugs. The immunoglobulin fractions containing the anticoagulant activity were isolated and characterized. A search for lupus inhibitor was carried out in 96 consecutively examined patients, but no further cases were found.

[Diagnostic problems in spontaneous bacterial peritonitis].

In spontaneous bacterial peritonitis (SBP) the ascitic fluid culture (certain criterion of diagnosis) may be negative despite an evident clinical and biochemical picture. Therefore the diagnosis may be sometimes more "probable" than "certain". The authors performed a comparative analytical study--from a clinical, biochemical and prognostic point of view--between a group of 10 "probable" SBP (10 cirrhotic pts.

Role of hepatitis B virus infection in chronic liver disease of diabetic patients: a case-control study.

In the literature there is no agreement on the prevalence of chronic liver disease (CLD) and the role of hepatitis B virus (HBV) infection in diabetics. We undertook an epidemiological case-control study of the prevalence of CLD and HBV infection in 394 diabetics and 265 healthy subjects from Seriate and Como. The results did not show any significant differences between: 1) the prevalence of CLD in the diabetic population and in controls (4.