Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

Background  

Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study.     

Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy

Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR)=6.31; p=0.0009), multiple primary melanomas (RR=3.43; p=0.0014), and early onset age (RR=4.56; p=0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.     

VEGF-D is expressed in activated lymphoid cells and in tumors of hematopoietic and lymphoid tissues

Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that activate the Vascular Endothelial Growth Factor Receptor (VEGFR)-2 and VEGFR-3, which are mainly expressed in blood and lymphatic vessels. Here we have analyzed by using monoclonal antibodies, the expression of VEGF-D and its cognate receptor VEGFR-3 in normal and pathologic bone marrow and lymph node biopsies. This analysis revealed that VEGF-D is expressed in B cells of the germinal centers, scattered B and T blasts, myeloid progenitors, acute leukemia, several types of non Hodgkin lymphoma, and classical Hodgkin's lymphoma. In normal tissues VEGFR-3 was only expressed in fenestrated capillaries of bone marrow and in lymphatic vessels of lymph nodes, while in VEGF-D expressing tumors newly formed vessels, but not malignant cells, showed high VEGFR-3 expression. These data suggest that VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues.     

Effect of chronic nicotine administration on the rat lung and liver: beneficial role of melatonin

Cigarette smoking is common in societies worldwide and has been identified as injurious to human health. The current study was designed to investigate the protective effect of melatonin, a radical scavenger and antioxidant, on nicotine-induced oxidative stress and morphological changes in the lung and liver of the rats. Three groups of male rats (controls, nicotine-treated [0.5 mg/kg], and nicotine plus melatonin [10 mg/kg] were used in this study. Levels of lipid peroxidation (LPO) products, superoxide dismutase (SOD) and glutathione (GSH) activity were measured in the tissue homogenates. Immunohistochemical and histological changes were also examined. The results revealed an increase in LPO and decrease in both SOD and GSH activity in the lung and liver homogenates on nicotine-treated rats. Melatonin administration to nicotine-treated rats attenuated the increase in LPO products and restored the SOD activity and GSH levels. The immunohistochemical and histological examination demonstrated marked increase in the immunoreactivity of nitrotyrosine, a specific "footprint" of peroxynitrite, and tissue damage in the lung and liver of nicotine-administered animals. Again, melatonin treatment reduced both nitrotyrosine reactivity and tissue damage associated with nicotine administration. These results, along with previous observations, suggest that melatonin may be useful in combating free radical-induced oxidative stress and tissue injury that is a result of nicotine toxicity.     

Glecaprevir/Pibrentasvir is safe and effective in Italian patients with chronic hepatitis C aged 75 years or older: A multicentre study

Background

Glecaprevir and Pibrentasvir (G/P) determine high rates of sustained virological response (SVR) with optimal safety profile in patients with chronic hepatitis C virus (HCV) infection. The efficacy and safety of G/P in Caucasian patients aged 75 years and older have not been widely analysed.

Methods

This is a retrospective multicentre real-world study enrolling all consecutive patients 75 years and older who received G/P between October 2017 and January 2022 at five referral centres in Italy. SVR was analysed by intention-to-treat (ITT) and per-protocol analyses (PP).

Results

A total of 570 patients met the inclusion criteria and were analysed: mean age was 80 (75–97) years, 356 (62%) were females, 52% (298/570) had HCV-1, 44% (252/570) had HCV-2 and 137 (24%) patients had liver cirrhosis. Four hundred and sixty-three (81%) patients were taking at least one concomitant drug, with 144 (25%) taking ≥5 concomitant drugs. G/P was given for 8 weeks in 488 patients (86%). During treatment, 48 patients (8%) reported side effects, with 10 (2%) patients discontinuing treatment prematurely. Two patients developed treatment-unrelated serious adverse events. Overall, the SVR rate was 97.9% (558/570) by ITT analysis and 99.6% (558/560) by PP analysis. SVR rates remained consistently high among subgroup analysis stratified by genotype, treatment duration, fibrosis stage and concomitant medications.

Conclusions

Treatment with G/P achieved 97.9% SVR rates in HCV patients older than 75 years of age. Safety was optimal with only 2% of patients discontinuing early.     

Modulation of nigral dopamine signaling mitigates parkinsonian signs of aging: evidence from intervention with calorie restriction or inhibition of dopamine uptake

GeroScience - Identifying neurobiological mechanisms of aging-related parkinsonism, and lifestyle interventions that mitigate them, remain critical knowledge gaps. No aging study, from rodent to...     

Spinal muscular atrophy and progressive myoclonic epilepsy: one case report and characteristics of the epileptic syndrome

INTRODUCTION: Spinal muscular atrophies (SMAs) are a group of degenerative diseases primarily affecting the anterior horn cells of the spinal cord and motor cells of cranial nerve nuclei. Even if the clinical picture is mainly dominated by the diffuse muscular atrophy, in some cases, patients may show associated, atypical clinical features ("SMA plus"). In particular, the association of SMA and progressive myoclonic epilepsy (PME) has been rarely described. CASE REPORT: We present the clinical and electrophysiological data of a boy with childhood-onset SMA associated with PME and reviewed cases of the literature. CONCLUSION: The association of SMA with PME may constitute a separate and, probably, genetically independent syndrome with unique clinical and electroencephalographic findings or, at least, a variant of a neurodegenerative or metabolic disease, due to yet unknown causes.     

Tumor Necrosis Factor‐Related Apoptosis‐Inducing Ligand (TRAIL) and Its Death Receptor (DR5) in Peyronie's Disease. A Biomolecular Study of Apoptosis Activation

IntroductionPeyronie's disease (PD) is a connective tissue disorder of tunica albuginea (TA), a thick fibrous sheath surrounding the corpora cavernosa of the penis. Relatively, little is known about the disease itself.AimTo investigate whether the apoptosis cascade in degenerated and macroscopically deformed TA from men with PD is activated through the extrinsic pathway, by assessing the immunoexpression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and its death receptor, DR5.MethodsTA plaques from 15 men with PD and from four unaffected men were processed for TRAIL and DR5 immunohistochemistry and Western blot analysis.Main Outcome MeasuresA greater understanding of the pathophysiology of PD through a molecular approach, to gain insights that may lead to novel forms of treatment.ResultsActivation of the apoptosis mechanisms through the extrinsic pathway was demonstrated by TRAIL and DR5 overexpression in fibroblasts and myofibroblasts from affected TA.ConclusionThe finding that apoptosis activation in TA plaques occurs, at least in part, via the extrinsic pathway may help devise novel therapeutic options for these patients. Loreto C, Barbagli G, Djinovic R, Vespasiani G, Carnazza ML, Miano R, Musumeci G, Sansalone S. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and its death receptor (DR5) in Peyronie's disease. A biomolecular study of apoptosis activation. J Sex Med 2011;8:109–115.