Hyperthermic Perfusion 16 Years After its First Clinical Applications

It is known that above-normal temperatures (42°-42.5°C) provoke selective damage to neoplastic cells. We used heated circulating blood as a method for heat transfer on patients with limb tumors. From October 1964 to December 1979, we treated a total of 198 patients with hyperthermic perfusion for melanoma of the limbs (91), osteosarcoma (57), and soft tissue sarcoma (50). For melanoma patients, the five-year survival rate, excluding Stage IV, was 60%. For patients with soft tissue sarcoma, the five-year survival rates were 53% and 56% for hyperthermic perfusion and hyperthermic antiblastic perfusion. respectively. For 29 patients with osteosarcoma, hyperthermic perfusion was combined with systematic amputation ofthe limb for a 60% survival rate over a five-year period. Newer studies with osteosarcoma patients involve a multistep treatment that saves the tumor-bearing limb without reducing survival rates. Our 16-year clinical trial demonstrates that hyperthermia is effective in curing some tumors of the limbs, especially osteosarcoma and melanoma. We believe that perfusion remains the most reliable heat transfer method for loco-regional treatment and perhaps even for whole-body treatment for limb tumors

Portuguese version of Duke Religious Index: DUREL

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A multidisciplinary expert opinion on CINV and RINV, unmet needs and practical real-life approaches

Introduction: A range of combination chemotherapy regimens are currently used in clinical practice. However, international antiemetic guidelines often only categorize the emetogenic potential of single agents rather than the emetogenicity of combination chemotherapy regimens. To manage the nausea and vomiting induced by antineoplastic combinations, guidelines suggest antiemetics that are appropriate for the component drug with the highest emetogenic potential. Furthermore, antiemetic guidelines generally do not consider the influence of other factors, including individual patient characteristics, on the emetic effects of cancer treatments. Similarly, the emetogenic potential of radiotherapy is stratified only according to the site of radiation, while other factors contributing to emetic risk are overlooked. Areas covered: An Expert Panel was convened to examine unresolved issues and summarize the current clinical research on managing nausea and vomiting associated with combination chemotherapy and radiotherapy. Expert opinion: The panel identified the incidence of nausea and vomiting induced by multi-drug combination therapies currently used to treat cancer at different anatomic sites and by radiotherapy in the presence of other risk factors. Based on these data and the clinical experience of panel members, several suggestions are made for a practical approach to prevent or manage nausea and vomiting due to chemotherapy regimens and radiation therapy

CD4+CD25+ lymphocyte subsets in chronic graft versus host disease patients undergoing extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP) has been used successfully for the treatment of chronic Graft versus Host Disease (cGvHD). However, the mechanism by which ECP exerts its protective effects remains elusive. Some recent observations have suggested a possible role of certain subsets of T lymphocytes with immunosuppressive properties (T-regulatory cells) that coexpress CD4 and high levels of the interleukin-2 receptor chain: CD4+CD25+ T lymphocytes. We studied whether ECP affects the percentage of these cells in the peripheral blood of patients with cGvHD. The study population consisted of 14 patients with cGvHD refractory to systemic steroids. On enrolment in each cycle of ECP, patients underwent clinical examination, blood chemistry analysis and other instrumental procedures to document and assess involvement of the various organs and systems. For cytofluorimetric identification and phenotyping of CD4+CD25+ T lymphocytes, peripheral blood samples were collected in EDTA anticoagulant before ECP, after 48 hours, and after 6 and 12 months from the start of treatment. The 14 patients in this study received a total of more than 300 cycles of ECP, with only minor side effects. The clinical outcome was negative in 2 patients and positive in 12 patients. Within-subject analysis indicated that the percentage of CD4+CD25+ T lymphocytes before ECP and after 12 months of treatment was significantly increased. Our study confirms that changes in the percentage of CD4+CD25+ T cells induced by ECP could be a central aspect in the cascade of immune events leading to the immunological and clinical effects of this treatment in patients with cGvHD

NGF-ome: its metabotrophic expression. Homage to Rita Levi-Montalcini

Nowadays, in the postgenome time, many "-ome" studies have emerged including proteome, transcriptome, interactome, metabolome, adipokinome, connectome. In this vein, the catchall term NGF-ome embodies all the actions of NGF in health and disease. Accordingly, the present Festschrift, also tabula gratulatoria, is to honor and acknowledge the contributions of the distinguished neuroscientist and magistra Rita Levi-Montalcini, the Nobel Prize winner-1986 for the discoverer of NGF. Today, NGF and another neurotrophin, brain-derived neuroptrophic factor (BDNF), are well recognized to mediate multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. These latter effects are involved in the maintenance of cardiometabolic homeostasis (glucose and lipid metabolism as well as energy balance, and cardioprotection). Circulating and/or tissue levels of NGF and BDNF are altered in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome, and type 3 diabetes/Alzheimer's disease). A hypothesis thus emerged that a metabotrophic deficit due to the reduction of NGF/BDNF availability and/or utilization may be implicated in the pathogenesis of cariometabolic and neurodegenerative diseases. The present challenge is therefore to cultivate a metabotrophic thinking about how we can modulate NGF/BDNF secretion and signaling for the benefit of human cardiometabolic and mood health.Biomedical Reviews 2010; 21: 25-29

Bioelectrical impedance analysis in patients with posterior vitreous detachment

OBJECTIVE: the purpose of the study is to assess body hydration in patients with posterior vitreous detachment (PVD) by bioelectrical impedance analysis (BIA). PVD, one of the most common eye diseases, is associated in both research and the collective image with reduced daily water intake, but this finding is not supported by strong evidence in the literature. PATIENTS AND METHODS: based on spectral domain optical coherence tomography (SD-OCT) evaluation, different PVD stages are identified: absent posterior vitreous detachment, partial posterior vitreous detachment (P-PVD), or complete posterior vitreous detachment (C-PVD). BIA is a simple, non-invasive bedside method used to assess body composition. patients underwent BIA and completed a floaters symptoms. 30 patients were enrolled and divided into two groups according to the degree of vitreous detachment, in P-PVD (n=12) and C-PVD (n=18). patients underwent BIA and completed a floaters symptoms questionnaire. BIA measured the resistance (R), reactance (Xc), phase angle (PhA), total body water (TBW), extracellular water (ECW), fat mass (FM), fat-free mass (FFM), and body cell mass Index (BCMI). finally, patients received a test to assess adherence to the mediterranean diet (mediterranean diet test score, MDTS) with the addition of daily water intake. RESULTS: relevant data were obtained from the BIA evaluation: the values of R and Xc were lower in the P-PVD group than C-PVD group (respectively 417.08±58.12 Ω vs. 476.94±51.29 Ω p=0.006 and 41.33±8.23 Ω vs. 50.61±7.98 Ω p=0.004). instead, patients in the P-PVD group reported higher values of TBW and ECW than C-PVD group (respectively 44.13±7.57 L vs. 37.96±6.27 L p=0.021 and 21.03±4.06 L vs. 17.24±2.63 L p=0.004). CONCLUSIONS: In the present study, we reported a significant correlation between vitreous pathology and anthropometric and BIA measurements

Trackins (Trk-targeting drugs): A novel therapy for different diseases

Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic routes and how can be they counteracted for therapeutic purposes? Human cells contain \u3e500 protein kinases and nearly 200 protein phosphatases, acting on thousands of proteins, including cell growth factors. We herein discuss neurotrophins with pathogenic or metabotrophic abilities, particularly brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), pro-NGF, neurotrophin-3 (NT-3), and their receptor Trk (tyrosine receptor kinase; pronounced track ). Indeed, we introduced the wor

Soluble CD40 ligand plasma levels in lung cancer

: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activatio

In the heart of adipobiology: cardiometabolic disease

Published on 1 December 1994 issue of Nature, the Jeffrey Friedman's discovery "gave leptin in the beginning" of the endocrine saga of adipose tissue. Onwards, studies on this tissue have enjoyed an explosive growth that conceptualized a novel field of research, adipobiology. Arguably, in the heart of adipobiology and adipopharmacology are studies focusing on the pathogenesis, prevention and therapy of cardiometabolic diseases (CMD) including atherosclerosis, hypertension, obesity, type 2 diabetes, metabolic syndrome (global cardiometabolic risk), and lipodystrophies.Biomedical Reviews 2009; 20: 1-5

SOS for Homo sapiens obesus

Published on 1 December 1994 issue of Nature, the Jeffrey Friedman's discovery "gave leptin in the beginning" of the endocrine saga of adipose tissue. Onwards, studies on this tissue have enjoyed an explosive growth that conceptualized a novel field of research, adipobiology. Arguably, in the heart of adipobiology and adipopharmacology are studies focusing on the pathogenesis, prevention and therapy of cardiometabolic diseases (CMD) including atherosclerosis, hypertension, obesity, type 2 diabetes, metabolic syndrome (global cardiometabolic risk), and lipodystrophies.Adipobiology 2010; 2: 5-8