From Tumor to Bone: Growth Factor Receptors as Key Players in Cancer Metastasis.

This review article explores the intricate correlation between growth factors and bone metastases, which play a crucial role in the development of several types of malignancies, namely breast, prostate, lung, and renal cancers. The focal point of our discussion is on crucial receptors for growth factors, including Epidermal Growth Factor Receptor (EGFR), Transforming Growth Factor-ß (TGFß), Vascular Endothelial Growth Factor Receptor (VEGFR), and Fibroblast Growth Factor Receptor (FGFR). These receptors, which are essential for cellular activities including growth, differentiation, and survival, have important involvement in the spread of cancer and the interactions between tumors and the bone environment. We discuss the underlying mechanisms of bone metastases, with a specific emphasis on the interaction between growth factor receptors and the bone microenvironment. EGFR signaling specifically enhances the process of osteoclast development and the formation of osteolytic lesions, especially in breast and lung malignancies. TGFß receptors have a role in both osteolytic and osteoblastic metastases by releasing TGFß, which attracts cancer cells and promotes bone remodeling. This is a crucial element in the spread of prostate cancer to the bones. The functions of FGFR and VEGFR in the processes of bone formation and tumor angiogenesis, respectively, highlight the complex and diverse nature of these interactions. The review emphasizes the possibility of targeted therapeutics targeting these receptors to interrupt the cycle of tumor development and bone degradation. Therapeutic approaches include focusing on the VEGF/VEGFR, EGF/EGFR, FGF/FGFR, and TGFß/TGFßR pathways. These include a variety of compounds, such as small molecule inhibitors and monoclonal antibodies, which have shown potential to interfere with tumor-induced alterations in bone. The text discusses clinical trials and preclinical models, offering insights into the effectiveness and constraints of various treatments. Ultimately, this study provides a succinct but thorough summary of the present knowledge and treatment strategies focused on growth factor receptors in bone metastases. This highlights the significance of comprehending the signaling of growth factor receptors in the microenvironment where tumors spread to the bones, as well as the possibility of using targeted therapies to enhance the results for cancer patients with bone metastases. The advancement of treating bone metastases hinges on the development of treatments that specifically target the intricate relationships between malignancies and bone.

Radiation exposure in cryoballoon ablation compared to radiofrequency ablation with three-dimensional electroanatomic mapping in atrial fibrillation patients.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) has become an established treatment to control symptoms. AF ablation either by cryoballoon or radiofrequency using three-dimensional (3D) electroanatomical mapping exposes patients and medical staff to increased doses of radiation. AIM: To compare radiation exposure in patients during cryoballoon ablation compared to 3D electro-anatomic mapping catheter ablation in AF patients. METHODS: A total of 30 patients referred for AF ablation underwent full history taking, 12-lead ECG, echocardiogram, and pulmonary vein isolation either by 3D mapping system or cryoballoon. Procedure duration and fluoroscopy time were collected and analyzed. Radiation exposure was measured using thermoluminescent dosimeters placed at different sites related to patients and medical staff. RESULT: The procedural time was statistically significantly longer with 3D mapping compared to cryoballoon but showed no significant difference regarding fluoroscopy time. There was a significantly higher radiation skin dose at the right scapular area in the cryoballoon ablation group, in addition to higher peak skin dose compared to the 3D mapping ablation group. There was no statistically significant correlation between peak skin doses and fluoroscopy duration but a statistically significant correlation between peak skin dose and usage of high frame rate and the high dose area product. CONCLUSION: Cryoballoon ablation was found to be associated with higher peak skin radiation doses especially in the right scapular area. Knowing dose area product and peak skin dose is more important than fluoroscopy time alone.

Efficacy and safety of intracoronary verapamil versus sodium nitroprusside for the prevention of microvascular obstruction during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

OBJECTIVE: The aim of this study was to compare the role of intracoronary (IC) verapamil versus sodium nitroprusside (SNP) in the prevention of microvascular obstruction (MVO) during a primary percutaneous coronary intervention (pPCI). BACKGROUND: A head-to-head comparison between verapamil and SNP in the prevention of MVO lacks evidence. PATIENTS AND METHODS: Sixty patients with ST-segment elevation myocardial infarction were randomized to receive IC verapamil (n=30) versus SNP (n=30) during pPCI. The primary outcome was the incidence of angiographic MVO as defined by Thrombolysis In Myocardial Infarction flow less than 3 or Thrombolysis In Myocardial Infarction flow 3 with myocardial blush grade less than 2. The secondary outcomes were the percentage of ST-segment resolution on 12-lead ECG, left ventricular ejection fraction and wall motion score index by two-dimensional echocardiography at 3-5 days after pPCI, as well as major adverse cardiovascular events at 30 days. Safety outcomes were the incidence of hypotension and/or bradycardia during pPCI. RESULTS: Verapamil was associated with lower incidence of angiographic MVO compared with SNP (13.3 vs. 40%, respectively; P=0.02), as well as superior ST-segment resolution greater than or equal to 70% (33.3 vs. 6.7%, respectively; P=0.01). There was a trend towards improved left ventricular ejection fraction with verapamil (42.6±4.9 vs. 40.4±4.7%, respectively; P=0.09), but with similar wall motion score index (1.43±0.1 vs. 1.45±0.2, respectively; P=0.14). Both groups had similar 30-day major adverse cardiovascular events (3.3 vs. 6.7%, respectively; P=0.55). Verapamil was associated with lower incidence of hypotension compared with SNP (3.3 vs. 20%, respectively; P=0.04). CONCLUSION: In pPCI, IC verapamil results in significant improvements in MVO with a better safety profile compared with SNP. Larger trials should be conducted to confirm these results.

Early Repolarization Pattern Is Associated with Increased Risk of Early Ventricular Arrhythmias during Acute ST Segment Elevation Myocardial Infarction.

BACKGROUND: Early repolarization (ER) and acute ST segment elevation myocardial infarction (STEMI) are sharing the pathophysiology of J wave syndromes. It is speculated that early ventricular arrhythmias (VAs) during STEMI may be predisposed by ER. Our aim was to study the association between ER pattern and risk of VAs during acute STEMI. METHODS: The study included 102 male patients with acute STEMI who were divided into two groups: cases and controls. Cases included 52 patients with sustained VAs during the first 48 hours from the onset of STEMI, while controls included 50 patients with no VAs. On 12-lead surface electrocardiogram, ER was defined as ≥ 1 mm elevation of J point in at least two inferior or lateral leads with or without ST segment elevation. RESULTS: Mean age was 48.44 ± 10.08 years and mean left ventricular ejection fraction (LVEF) was 42.25 ± 11.1%. ER pattern was more frequent in cases than controls (29 vs 14 patients, P = 0.008). Notched J wave (P = 0.0007) and horizontal ST segment (P = 0.033) were more frequent in cases than controls. On adjusted regression model, LVEF (OR: 0.95, 95% CI: 0.91-0.99, P = 0.015) and ER (OR: 3.39, 95% CI: 1.41-8.12, P = 0.006) could predict VAs, while QTc interval (P = 0.24) and QTd (P = 0.86) did not have predictive effect. Inferior/inferolateral and global ER pattern (P = 0.044 and 0.031 respectively), notched J wave (P = 0.001), increasing J wave amplitude (P = 0.042), and ST segment elevation (P = 0.001) were associated with a higher risk of VAs. CONCLUSIONS: ER is associated with increased risk of VAs in the setting of acute STEMI.