20 research outputs found
Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGFβ-Induced EMT in Human Non-Small Cell Lung Cancer
Get PDFGrowth factors and cytokines released in the lung cancer microenvironment promote an epithelial-to-mesenchymal transition (EMT) that sustains the progression of neoplastic diseases. TGFβ is one of the most powerful inducers of this transition, as it induces overexpression of the fibronectin receptor, αvβ6 integrin, in cancer cells which, in turn, is strongly associated with EMT. Thus, αvβ6 integrin receptors may be exploited as a target for the selective delivery of anti-tumor agents. We introduce three novel synthesized conjugates, in which a selective αvβ6 receptor ligand is linked to nintedanib, a potent kinase inhibitor used to treat advanced adenocarcinoma lung cancer in clinics. The αvβ6 integrin ligand directs nintedanib activity to the target cells of the tumor microenvironment, avoiding the onset of negative side effects in normal cells. We found that the three conjugates inhibit the adhesion of cancer cells to fibronectin in a concentration-dependent manner and that αvβ6-expressing cells internalized the conjugated compounds, thus permitting nintedanib to inhibit 2D and 3D cancer cell growth and suppress the clonogenic ability of the EMT phenotype as well as intervening in other aspects associated with the EMT transition. These results highlight αvβ6 receptors as privileged access points for dual-targeting molecular conjugates engaged in an efficient and precise strategy against non-small cell lung cancer
Cell-targeted c(AmpRGD)-sunitinib molecular conjugates impair tumor growth of melanoma
Get PDFDrug resistance and off-organ toxicity remain unsolved issues in chemotherapy of advanced-stage melanoma patients. Thus, the creation of new molecular conjugates able to combine a selective accumulation, high ability of internalization and signaling pathway inhibition, are highly requested. Recently, we reported a new class of molecular conjugates, compounds 1–3, where the anti-αVβ3 integrin peptidomimetic c(AmpRGD), which is a selective ligand for αVβ3 integrin, was covalently bound to the tyrosine kinase inhibitor sunitinib. Here, we report that these c(AmpRGD)-sunitinib conjugates and, in particular, compound 3, are selectively internalized by human melanoma cells through αVβ3 receptor-mediated endocytosis. Compound 3 is more effective than sunitinib in reducing in vitro melanoma cells proliferation, cloning efficiency, migration, and invasion. More interestingly, compound 3 is able to significantly reduce the growth of xenografted melanoma tumor developed in immune-compromised mice, more efficiently than an equimolar dose of sunitinib. Indeed, its targeting ability was demonstrated by the selective localization at the tumor level with respect to healthy tissues. Thus, c(AmpRGD)-sunitinib conjugates such as compound 3 could serve as intriguing multiple-target agents to selectively reach melanoma cells and interfere with the progression of the disease
[Management of patients with type 2 diabetes during cardiac prevention and rehabilitation. An expert opinion from the Italian Alliance for Cardiovascular Rehabilitation and Prevention (ITACARE-P)]
No full textPatients with diabetes, regardless of their cardiovascular disease and their index event, are more and more often referred to Cardiac Rehabilitation Units. These patients usually show high or very high cardiovascular risk, marked disability and poor quality of life. Furthermore, those with older age, frailty, and female sex have even more rehabilitative needs, thus requiring fine individualized approaches. Consequently, in order to identify their therapeutic goals, the glycemic target should be pursued together with the effective reduction of the global cardiovascular risk. Modern exercise protocols are based on the synergic effect of both aerobic and strength training of moderate and high effort intensities, in order to achieve improvements of cardiorespiratory fitness and glycemic values as well. Exercise training and nutritional intervention are strictly related during the rehabilitation program, thus promoting better lifestyle in the long term too. New antidiabetic drugs (such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists) should be included into a specific "patient journey" along with other core components of the rehabilitation program. Therefore, the active role of all allied professionals (namely nurses, physiotherapists, dietitians and psychologists) is essential to the success of the cardiometabolic team. Diabetes should be routinely included in the outcome evaluation of cardiac rehabilitation programs and in every follow-up plan through a successful crosstalk among cardiologists, diabetologists and patients
Position paper ITACARE-P/FADOI on the referral from internal medicine to cardiac rehabilitation: Executive summary and factsheet
No full textThe Italian Association for Cardiovascular Rehabilitation and Prevention (ITACARE-P) and the Italian Federation of Associations of Hospital Doctors on Internal Medicine (FADOI) released a joint position paper to guide referrals of cardiovascular patients discharged from Internal Medicine (IM) wards to Cardiac Rehabilitation (CR) facilities. The document provides rationale and operative recommendations for appropriateness (i.e. qualifying diagnoses) and priority criteria to overcome the mismatch between potential demand and effective supply of CR programmes. In case of no-referral due to logistic barriers, the document recommends the adoption of best alternatives to CR for disability reduction, better prognosis, and improvement of quality of life. The joint position paper is also aimed to promote the consideration of IM as a potential stakeholder of CR
Cardiac contractility modulation in patients with heart failure: The added value of cardiac rehabilitation in identification, management, and follow-up
No full textHome defibrillation: A feasibility study in myocardial infarction survivors at intermediate risk of sudden death
No full textBackground Out-of-hospital cardiac arrest occurs at home in 65-80% of cases and is often witnessed. We designed a study to explore the feasibility of a home defibrillation program (a) evaluating the retention of cardiopulmonary resuscitation and automated external defibrillators (AED) use skills (BLSD) (b) assessing the impact on anxiety, depression, and quality of life and (c) recording the critical issues emerging from program implementation. Methods Thirty-three post-myocardial infarction patients and their 56 relatives received BLSD training and an AED. Assessment of BLSD skills, levels of anxiety, and depression and quality of life were scheduled every 3 months for 1 year or until a common stopping date. Results Overall BLSD score was 26 +/- 3 at baseline vs. 22 +/- 5 at 3 months (P < .0001), 21 +/- 6 at 6 months (P < .0001), 22 +/- 4 at 9 months (P < 0.0001) and 23 +/- 5 at 12 months (P = .001). Conversely, the BLSD component "AED use"-remained stable throughout the study. Quality of life, anxiety, and depression scores remained constant. Compliance to BLSD retraining sessions and AEDs checks decreased over time and was influenced by a concomitant clinical appoinment. Conclusions BLSD performance of families of post-myocardial infarction patients decreases over time, even though the ability to operate AEDs appears to be the least affected component. Compliance with retraining sessions and AED checks declines over time and is improved if they are combined with clinical appointments. The implementation of a home defibrillation program does not affect anxiety, depression, or the quality of life
Therapeutic Inertia in Dyslipidemia Management for Secondary Cardiovascular Prevention: Results from the Italian ITACARE-P Network
Get PDF: Background/Objectives: This study assessed the proportion of secondary cardiovascular prevention patients who achieved low-density lipoprotein (LDL) cholesterol targets as per the 2019 ESC/EAS Dyslipidemia Guidelines. We also evaluated whether lipid-lowering therapies (LLTs) were adjusted in patients not meeting targets and analyzed the likelihood of these modifications achieving recommended levels. Methods: A multicenter, cross-sectional observational study retrospectively reviewed medical records of 1909 outpatients in 9 Italian cardiac rehabilitation/secondary prevention clinics from January 2023 to June 2024. Inclusion criteria included prior atherosclerotic cardiovascular disease (ASCVD) and recent LDL-cholesterol levels. Data included demographics, ASCVD presentation, lipid profiles, and LLTs. Patients at very high risk had LDL targets of ≤55 mg/dL, or ≤40 mg/dL for recurrent events within 2 years. Clinicians' approaches to LLT modification in patients not at target were recorded, with LLT efficacy estimated based on percentage distance from LDL-cholesterol targets. Results: Of the 1909 patients, 41.3% met the LDL-cholesterol target. Predictors of achieving targets included male gender, cardiac rehabilitation, recent acute coronary syndrome, diabetes, and triple therapy (statin + ezetimibe + PCSK9 inhibitors). Conversely, a target of ≤40 mg/dL, lack of therapy, and monotherapy were negative predictors. Among 1074 patients not at target, LLT modifications were proposed for 48.6%. Predictors of LLT modification included recent ASCVD events, cardiac rehabilitation, and greater percentage distance from the LDL target, while advanced age and an LDL target of ≤40 mg/dL were negative predictors. However, only 42.3% of modified therapies were predicted to be effective in reaching LDL targets. Conclusions: Despite 2019 ESC/EAS guidelines, a significant proportion of high-risk patients did not achieve LDL targets, and proposed LLT modifications were often insufficient. More intensive LLT regimens are needed to improve outcomes in this population
ITACARE-P/SIGG/SIGOT/SICGE position paper on elderly cardiac patient referral to cardiac rehabilitation
No full textThe Italian Association for Cardiovascular Rehabilitation and Prevention (ITACARE-P) together with the Società Italiana di Gerontologia e Geriatria (SIGG); Società Italiana di Geriatria Ospedale e Territorio (SIGOT); SICGE, Società Italiana di Cardiologia Geriatrica (SICGE) released a joint position paper to guide referrals of elderly cardiovascular patients discharged from Geriatric wards to Cardiac Rehabilitation (CR) facilities. The document provides rationale and operative recommendations for appropriateness (i.e. qualifying diagnosis) and priority criteria to overcome mismatch between potential demand and effective supply of CR programmes. In case of no-referral due to logistic restraints, the document recommends the adoption of best alternatives to CR for disability reduction, better prognosis, and improvement of quality of life. The joint position paper is also aimed at promoting the consideration of Geriatric Medicine as a potential stakeholder of CR
Usefulness of transthoracic echocardiogram in management of cardiac involvement in large B-Cell lymphoma: a case report
Get PDFPrimary lymphoma often involve the heart, especially the right side. Prompt diagnosis is necessary to start the right therapy and decrease symptoms and death risk rate. Transthoracic echocardiogram is the first line exam to perform when symptoms are suspicious of mediastinal mass
