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Made available in DSpace on 2022-04-29T08:46:55Z (GMT). No. of bitstreams: 0 Previous issue date: 1998-10-01 Supersymmetric quantum mechanics can be used to obtain the spectrum and eigenstates of one-dimensional Hamiltonians. It is particularly useful when applied to partially solvable potentials because a superalgebra allows us to compute the spectrum state by state. Some solutions for the truncated Coulomb potential, an asymptotically linear potential, and a nonpolynomial potential are shown to exemplify the method. Inst. Biociencias, Letras C. Univ. Estadual Paulista, Rua Pamplona 145, BR-01405-900 São Paulo Faculdade de Tecn. de Sao Paulo Univ. Estadual Paulista, Rua Pamplona 145, BR-01405-900 São Paulo Inst. Biociencias, Letras C. Univ. Estadual Paulista, Rua Pamplona 145, BR-01405-900 São Paulo Faculdade de Tecn. de Sao Paulo Univ. Estadual Paulista, Rua Pamplona 145, BR-01405-900 São Paulo

Palliative chemotherapy significantly reduces mortality in patients with stage IV colon cancer, but is less prescribed with rising age. In this paper, we highlight the pattern of palliative treatment and possible effects on survival among elderly patients.From January to December 2004, 78 files on the management of stage IV colorectal cancer (CRC) patients over 70 years, collected from 10 Italian Centres, were retrospectively examined. Determinants of receipt of palliative chemotherapy and their relation to toxicity and survival were considered.The proportion of elderly patients receiving first-line palliative chemotherapy was 98.7% and it was evaluated according to age, gender, educational level and comorbidities; patients receiving second-line therapy comprised 47.4%, those receiving third-line therapy 14.1% and those treated with a fourth-line therapy totalled 2.6%. Forty-one percent of patients received best supportive care (BSC) alone.In Italy, a proportion of elderly patients with metastatic chemonaive CRC are usually treated with a tolerability and overall survival similar to those for the younger population. Among progressive patients after second-line therapy, 45.8% usually undergo third line therapy; the remaining 54.2% undergo BSC.

Adjuvant 5-fluoruracil-based chemotherapy significantly reduces mortality in patients with stage II-III colon cancer, but is less prescribed with rising age. In this study we were interested in the pattern of adjuvant treatment and possible effects on survival among elderly patients.From January to December 2004, 63 questionnaires on the management of stage II-III resected colon cancer patients aged over 70 years, collected from 10 Italian Centres, were retrospectively examined. Determinants of receipt of adjuvant chemotherapy and their relation to survival were considered.The proportion of elderly patients receiving adjuvant chemotherapy was 79.4%, distinct of age, gender, educational level and comorbidities. Grade 3-4 toxicities were the following: haematological in 4 (8.5.%) patients, mucositis in 4 (8.5%), diarrhoea in 2 (4.2%) and nausea in 1 (2.1%). The disease-free survival (DFS) and overall survival (OS) at two years were 79.9% and 95.6%, respectively. Due to the paucity of events, the impact of prognostic factors (patient's age and comorbidity, tumour stage and grade) on DFS and OS could not be assessed.An increasing proportion of elderly patients with colon cancer may be treated with a tolerability and OS similar to those observed in the younger population. Development of age-based guidelines and increased awareness of both physicians and patients through education is important to prevent undertreatment of those elderly patients who are eligible for chemotherapy.

Cardiovascular toxicity in cancer patients receiving chemotherapy remains one of the most undesirable side effects, limiting the choice of the most efficient therapeutic regimen, including combinations of different anticancer agents. Anthracyclines (doxorubicin) and antimetabolites (5-fluorouracil (5-FU), capecitabine) are among the most known agents used in breast cancer and other neoplasms and are associated with cardiotoxic effects. Extra-virgin olive oil (EVOO) is rich in polyphenols endowed with antioxidant cardioprotective activities. Olive mill wastewater (OMWW), a waste product generated by EVOO processing, has been reported to be enriched in polyphenols. In this study, we investigated the activities of polyphenol-rich extract from OMWW, A009, in cooperation with chemotherapy on two breast cancer cell lines, namely, BT459 and MDA-MB-231, in a cardio-oncology perspective. The effects of A009 on cardiac cells were also investigated with and without chemotherapeutic agents. Cell viability was determined on BT459 and MDA-MB-231 (i.e., breast cancer cells) and H9C2 (i.e., rat cardiomyocytes) cells, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A spheroids assay was used as a 3D in vitro model on BT459 and MDA-MB-231 cells. For in vivo studies, the murine sponge assay of angiogenesis was used as a model of breast cancer-associated vascularization. The embryo of Danio rerio (zebrafish) was used to detect the cardioprotective activities of the OMWW. We found that the A009 extract exhibited antiangiogenic activities induced by breast cancer cell supernatants and increased T-cell recruitment in vivo. The combination of the OMWW extracts with doxorubicin or 5-FU limited BT459 and MDA-MB-231 cell viability and the diameter of 3D spheroids, while mitigating their toxic effects on the rat H9C2 cardiomyocytes. Cardioprotective effects were observed by the combination of OMWW extracts with doxorubicin in zebrafish embryos. Finally, in human cardio myocytes, we observed 5-FU-induced upregulation of the inflammatory, senescence-associated cytokine IL6 and p16 genes, which expression was reduced by OMWW treatment. Our study demonstrates that the polyphenol-rich purified OMWW extract A009 combined with cancer chemotherapy could represent a potential candidate for cardiovascular protection in breast cancer patients, while increasing the effects of breast cancer chemotherapy.

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan&ndash, Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51&ndash, 10.88) and 11.57 months (95% CI 10.90&ndash, not reached (NR)) as second-line and 11.38 months (95% CI 5.79&ndash, NR) and NR (95% CI 11.51&ndash, NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib&ndash, nivolumab and 25.64 months and NR with nivolumab&ndash, cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39, 95% CI 1.24&ndash, 4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04&ndash, 2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33, 95%CI, 1.16&ndash, 4.69, p = 0.018) and Hb levels (HR = 3.12, 95%CI 1.18&ndash, 8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72, 95%CI 1.04&ndash, 7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

L’attuale conformazione del capitalismo s’inquadra come modello economico del libero mercato, inteso come ecosistema in grado di autoregolarsi. Sembrerebbe una condizione ottimale in cui le variabili della domanda, dell’inflazione e della disoccupazione funzionano alla stregua di forze naturali e che, mediante “aggiustamenti” spontanei, sono in grado di assicurare l’equilibrio creando un mondo perfetto di piena occupazione, creatività e “crescita perpetua” (Hayek 1944; Friedman 1962). Questa teorizzazione ideologizza la dottrina economica e conserva i caratteri del fondamentalismo con cui, a livello sociale, sono costruiti i processi di legittimazione politica. Infatti se qualcosa nel mercato (e quindi socialmente) non funziona (ad esempio l’inflazione sale, la crescita diminuisce, ecc.), l’unica spiegazione plausibile è che il mercato non è abbastanza libero. Secondo tale orientamento, la soluzione, e dunque il modo per creare la società perfetta, consiste nell’applicazione più rigida delle norme fondamentali di libertà economica e nell’eliminazione di qualsiasi forma di ingerenza da parte dello Stato nell’economia come prescrizione universalmente valida per lo sviluppo; un nuovo progetto economico, dunque, che richiede: a) la liberalizzazione e la deregolamentazione delle transazioni economiche (nazionali e internazionali), b) la privatizzazione delle imprese statali e dei servizi forniti dallo stato e, addirittura, c) il trattamento della spesa pubblica per il benessere come costo della produzione internazionale, piuttosto che come fonte di domanda interna (Jessop 2002, 458-459). Si tratta di un modello nettamente in contrasto con tutte le forme di intervento pubblico e, quindi, con la “Teoria economica keynesiana” che prevede (in particolare nei periodi di crisi) interventi da parte dello Stato per incrementare la domanda globale anche in condizioni di deficit pubblico (Keynes 1920, 1936) e che considera lo spazio sociale in termini di mercato anche riguardo alle questioni legate al welfare (salute, istruzione, lavoro, ecc.), dove i problemi di bilanciamento tra bisogni sociali e allocazione di risorse scarse divengono evidenti. Un livello, quest’ultimo, in cui si manifestano aspettative sociali che determinano un trasferimento di responsabilità decisionale (e quindi del rischio) dall’economia alla politica, sebbene l’economia continui a dipendere dal fatto che siano assicurate le condizioni di pace, che il diritto venga tutelato e che le decisioni vincolanti vengano prodotte dalla politica (Luhmann 1983). Questa prassi supera il concetto di “mano invisibile” del liberalismo smithiano perché rappresenta, per certi versi, l’esito di sovrapposizioni tra sistema economico e sistema politico, ciò equivale ad una “intrasparenza” funzionale tra i sistemi che confonde il linguaggio e i codici della politica con quelli dell’economia generando nuove forme di esclusione sociale che, come risposta e sempre più spesso, si trasformano in populismi (Preite 2017). Il rancore cui il populismo dà voce non è altro che il prodotto di una incapacità di rappresentare e di dare risposte al disagio sociale che, lasciato a se stesso dalle forze politiche “razionali”, trova ascolto soltanto nei profeti del risentimento. Un fenomeno che crea distanza tra potere e società, una consapevole e indignata esclusione dal centro degli interessi economici. In tale prospettiva, i moderni populismi funzionano, dunque, come reti “fiduciarie” di inclusione sociale. Questo contributo si pone l’obiettivo di descrivere in che misura i nuovi populismi siano in grado di compensare la pressione delle aspettative rispetto a valori di inclusione sociale, con un approccio che parte dal superamento del tradizionale schema assiale centro/periferia per giungere all’analisi delle “reti fiduciarie” che entrano in campo.

BACKGROUND In the last 2 decades, new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. The aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs. METHODS Twenty-nine patients (27 affected by renal and 2 by thyroid cancer), received treatment with anti-VEGFR drugs. Brachial blood pressure (BP), central BP, carotid-femoral pulse wave velocity (cfPWV), augmentation index (Aix), and several echocardiographic markers of systolic and diastolic left ventricular functions including global longitudinal strain were measured before starting treatment (T0), after 2 (T1), and 6 weeks (T2) of treatment. RESULTS Anti-VEGFR treatment was accompanied by a significant increase of both peripheral (systolic BP +13±15.5mm Hg, diastolic BP +7.1±9.3mm Hg, P < 0.001) and central BP (systolic BP +14±14.2mm Hg, diastolic BP +7.3±10.4mm Hg, P < 0.001) and a significant raise of cfPWV (+1.3±1.8 m/sec, P = 0.003). There was also a significant alteration of markers of diastolic and subclinical left ventricular systolic function, including global longitudinal strain (-19.9±3.8% at T0, -17.8±2.6% at T2, P < 0.05). All the changes were already evident at T1, worsened at T2 in patients who maintained oncological treatment, but disappeared at T2 in patients in whom treatment was stopped. CONCLUSIONS All the changes regarding BP and cfPWV appear early after treatment initiation and seem to be reversible if treatment is stopped, instead diastolic and systolic left ventricular function are persistently altered by anti-VEGFR drugs.

OBJECTIVE: In the last two decades new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. Aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs. DESIGN AND METHOD: 29 patients (27 affected by renal and 2 by thyroid cancer), received treatment with antiVEGFR drugs. Hemodynamic, non invasive arterial investigation (Pulse Wave velocity -cfPWV-, Augmentation Index-Aix- and Aortic Pressure) and echocardiography with global longitudinal strain (gLS) were performed before starting therapy (T0), after 2 (T1) and 6 weeks (T2). Oncologic outcome was determined by the assessment of the neoplastic lesions at CT scans, according to Response Evaluation Criteria in Solid Tumors Guidelines. RESULTS: A significant increase of both peripheral and central blood pressure (BP) was observed. We documented a significant raise of cfPWV from T0 (9.9 ± 2.5m/sec) to T1 (10.6 ± 2.3m/sec); at T2 cfPWV still increased in patients who continued treatment (10.8 ± 2.3m/sec), while decreased in patients who stopped therapy (9.8 ± 1.9m/sec). At the on-treatment CT scan (available in 22 patients) 12 patients had a stable disease (StD), 5 showed a reduction of the lesions (responders -PR-) and 5 showed a disease progression (PD). PD patients showed a lower cfPWV at T2 than StD-PR patients (cfPWV: 9.3 ± 2.8 Vs 13.3 ± 1.5 m/sec; p value 0.02). Aix at T1 was higher in PD than in StD-PR (Aix: 36 ± 2.8% Vs 24.6 ± 9.2%; p value 0.02). CONCLUSIONS: Anti-VEGFR treatment is associated with a marked increase in both brachial and central BP. Moreover it early induces an aortic reversible stiffening. The evidence that cfPWV and AIx changes are early and sensitive cardio-vascular effects of anti-angiogenic treatment and that disease progression is associated with a concomitant come back to pre-treatment value of cfPWV and a further increase in augmentation index, suggests their possible role on oncologic outcome