Combination radium-223 therapies in patients with bone metastases from castration-resistant prostate cancer: A review.

Chemotherapeutic agents (docetaxel, cabazitaxel), hormonal therapies (abiraterone, enzalutamide) and radium-223 improve survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Combinations of radium-223 with these agents or novel drugs have been investigated in order to improve survival and decrease bone-related morbidity. In mCRPC, clinical and preclinical data indicate that radium-223, abiraterone and enzalutamide have a direct effect on prostate cancer cells and bone microenvironment when administered as single agents. Initial results from studies of radium-223 and abiraterone, enzalutamide or docetaxel demonstrated efficacy without any safety concern in pre-treated mCRPC; however, this safety profile changed when radium-based combination therapies were administered in un-pretreated mCRPC. This review underline the biological rationale for combining radium strategies, investigating their effects on bone in terms of control of skeletal-related events and bone disease progression. The aim is to understand the possible reasons why different radium-based combination treatments can led to different clinical outcomes.

Cabozantinib Affects Osteosarcoma Growth Through A Direct Effect On Tumor Cells and Modifications In Bone Microenvironment.

Osteosarcoma (OS) is the most common primary malignant tumor of the bone. Due to its high heterogeneity and to survival signals from bone microenvironment, OS can resist to standard treatments, therefore novel therapies are needed. c-MET oncogene, a tyrosine-kinase receptor, plays a crucial role in OS initiation and progression. The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment. We tested different doses of CBZ in in vitro models of OS alone or in co-culture with bone cells in order to reproduce OS-tumor microenvironment interactions. CBZ is able to decrease proliferation and migration of OS cells, inhibiting ERK and AKT signaling pathways. Furthermore, CBZ leads to the inhibition of the proliferation of OS cells expressing receptor activator of nuclear factor κB (RANK), due to its effect on bone microenvironment, where it causes an overproduction of osteoprotegerin and a decrease of production of RANK ligand by osteoblasts. Overall, our data demonstrate that CBZ might represent a new potential treatment against OS, affecting both OS cells and their microenvironment. In this scenario, RANK expression in OS cells could represent a predictive factor of better response to CBZ treatment.

[Use of a latissimus dorsi myocutaneous flap in locally advanced breast cancer]. / L'uso del lembo miocutaneo di gran dorsale nel carcinoma mammario localmente avanzato.

Locally advanced breast cancer has a poor prognosis. Skin infiltration, ulceration and invasion of the chest wall, in the absence of distant metastases, worsen dramatically the quality of life. The Authors report 4 cases of one time wide resection and reconstruction using a pedicled myocutaneous flap of latissimus dorsi. This technique allowed good and rapid palliation of local symptoms.

Manometric characteristics of the distal oesophageal sphincter and patterns of gastro-oesophageal reflux in healthy volunteers and patients.

Three manometric characteristics of the distal oesophageal sphincter (DOS; pressure, length below the respiratory inversion point, i.e., abdominal length, and overall length) were investigated in 10 healthy volunteers and in 66 patients with typical symptoms of gastro-oesophageal reflux (GOR) disease. The aim of the work was to correlate the DOS deficiency with symptoms, endoscopic oesophagitis and with specific patterns of GOR as determined by means of 24-hour oesophageal pH monitoring. The results showed that patients with and without GOR disease cannot be separated solely on the basis of the standard manometric test, even adopting more parameters besides the traditional DOS pressure measurement. A functional defect of the DOS may be hypothesized for those patients with an apparently normal DOS on standard oesophageal manometry.