Metronomic chemotherapy preserves quality of life ensuring efficacy in elderly advanced non small cell lung cancer patients

Metastatic non small cell lung cancers (NSCLC) are diseases with poor prognosis and platinum-based doublet chemotherapy still remains their standard cure. Elderly patients often present comorbidities that limit the utilization of this chemotherapy; therefore these patients should have a first-line treatment with low toxicity and capable to preserve the quality of life (QoL) but, at the same time, to ensure the best possible response. Furthermore, a first-line treatment allows patients to be fit for further treatments, prolonging overall survival. At this regard, metronomic chemotherapy can be an optimal choice for elderly, able to improve QoL and to obtain an optimal palliation. We retrospectively studied a cohort of 41 elderly advanced NSCLC patients with different histotypes, treated with metronomic chemotherapy (weekly carbo-paclitaxel or vinorelbine as single agent) as first choice and we analyzed the tolerability, the impact on QoL and the efficacy of these schedules: no toxicity of 3 and 4 grade was observed, together to a clinical benefit of 43%. We administered FACT-L test to evaluate QoL at baseline and after 4 months and found a significant improvement in all FACT-L parameters: physical, social, emotional and functional, confirming a QoL improvement. At a median follow-up of 20.2 months the progression free survival was of 6 months and the overall survival was of 15 months. These results suggest that metronomic chemotherapy can be an effective choice of treatment for elderly NSCLC patients and further trials with more patients are needed to confirm this proposal

Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer

Background: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. Methods: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab. Results: NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls; further- more, NRG1 and Gal-3 were significantly increased after chemotherapy and were predictive of mortality at 1 year. Conclusions: Circulating NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes for breast cancer patients

The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells

Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis

Restablecimiento de una nueva normalidad biomecánica en las graves deformidades de la rodilla

En las graves alteraciones morfo-estructurales de la rodilla, con inestabilidad en varusvalgus, las prótesis vinculadas a bisagra simple, tendían a fallar. El presente trabajo se propone evidenciar que, en tales situaciones, la prótesis vinculada a rotación representa la solución más idónea para el restablecimiento de una nueva normalidad. 18 pacientes (13 mujeres y 5 hombres) con edad media de 68 años han sido sometidos a intervención para colocar prótesis de rodilla. Ha sido utilizado el implante Endo-Model® de Waldemar Link®, prótesis vinculada a rotación. El follow-up medio es de 19 meses con controles a 2, 3, 6 y 12 meses y después anuales. Los resultados han sido: óptimo para 17 pacientes y bueno para 1 paciente, en el cual se ha verificado la ruptura post-operatoria del tendón cuadricipital. Nuestra casuística muestra resultados comparables a los de otros autores. No hemos tenido movilizaciones asépticas o sépticas, ni complicaciones médicas intraoperatorias y post-operatorias. Consideramos que, en presencia de la correcta indicación clínica, la utilización de la prótesis vinculada a rotación es preferible a la de deslizamiento porque disminuye el riesgo de una movilización precoz del implante y del desgaste anormal de los componentes protésicos, restableciendo una nueva normalidad biomecánica.Peer Reviewe

The influence of packaging on the sensorial evolution of white wine as a function of the operating conditions adopted during storage

With the aim to determine the influence of packaging in preserving the quality of wine, in this research project the sensorial evolution of a white table wine stored in different packaging materials (glass bottles provided with different closures; bag-in-box (BiB) containers; tetrabricks®) and different volumes (2 volumes for each packaging) has been evaluated over a period of 12 months. For each packaging solution two different temperature levels (4° and 20°C) were also maintained throughout the storage period. The preliminary results obtained indicate that wine evolution (characterized by both sensorial and chemical parameters) might be greatly influenced by the packaging characteristics. In particular in glass bottle, the crown cap allowed the best storage conditions for wine, closely followed by natural cork, while the wine maintained in tetrabricks® showed the worst organoleptic profile with the maximum level of oxidation and the highest evolutionary state, closely followed by the wine packaged in BiB containers

EGFR-Targeted Antibody–Drug Conjugate to Different Aminobisphosphonates:Direct and Indirect Antitumor Effects on Colorectal Carcinoma Cells

Antibody––drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a “biological missile” that can destroy tumor cells while increasing the therapeutic index and decreasing toxicity. One of the most critical factors in ADC design is selecting a target antigen that is highly expressed on the surface of cancer cells. In this study, we conjugated Cetuximab (Cet), a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to aminobisphosphonates (N-BPs) such as ibandronate (IBA) or risedronate (RIS) or zoledronate (ZA). Cetuximab is administered to patients with metastatic colorectal carcinoma (mCRC) with a wild-type (WT) EGFR transduction pathway. Also, it is well established that N-BPs can trigger the antitumor activity of Vδ2 T cells in both in vitro and in vivo experimental models. The resulting ADCs were added in co-culture to assess the effect on CRC cell line proliferation and sensitivity to Vδ2 T antitumor lymphocytes in comparison with the native antibody. These assays have been performed both in conventional and 3D spheroid cultures. We found that all three ADCs can increase the inhibitory effect on cell proliferation of the WT-EGFR cell line Caco-2 while only Cet-RIS and Cet-ZA can increase the cytotoxicity mediated by Vδ2 T cells against both WT and EGFR-mutated CRC cell lines (Caco-2, DLD-1, and HCT-116). Also, the ADCs can trigger the cell proliferation of Vδ2 T cells present in peripheral blood and tumor specimens. Our findings indicate that anti-EGFR antibodies bound to N-BPs can improve the antitumor effects of the native antibody possibly increasing the therapeutic effect.</p

Production of Red Wine Polyphenols as Ingredient for the Food and Pharmaceutical Industry

Abstract A selected reverse osmosis based industrial process was developed and validated at pilot plant scale for producing red wine polyphenols dealcoholized and/or concentrated solutions and pastes, starting from red wine as raw material. These ingredients can be used for making new functional products for the food and beverages industry. Comparison with competitive technologies is made, accounting for energy consumption and process operating parameters to avoid damage to the RWP antioxidant functionality. In addition criteria for selecting between different available raw materials and different possible products are discussed with reference to up-stream and down-stream operations, dietary reference intake (DRI) and shelf-life of each ingredients

Balloon pulmonary angioplasty after pulmonary thromboendarterectomy

.Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH) as it can remove the chronic, fibrotic, flow-limiting organized thrombi within the pulmonary arterial bed, addressing the primum movens of the disease (1). Despite significant improvement in all haemodynamic parameters, residual pulmonary hypertension (PH) is frequent after PTE, ranging from 17% to 31% (2,3). There is no clear definition of residual PH after PTE, and the actual incidence of this condition has been difficult to quantify. Usually, moderate residual PH is well tolerated by patients and, as shown by data from the United Kingdom cohort, clinically relevant residual PH after PTE mainly occur when the mean pulmonary arterial pressure (mPAP) is greater than 30–35 mmHg (3). The risk of persistent/recurrent PH in the long-term underlines the importance of a systematic patient follow-up, even after PTE. Balloon pulmonary angioplasty (BPA) has been developed as a compassionate procedure for symptomatic patients with CTEPH who are ineligible for surgery or with persistent/recurrent PH after PTE. BPA is not able to remove clots as PTE, but it is able to restore the flow by fragmenting the thrombotic and fibrotic material, resulting in hemodynamic and clinical improvement. Selection of good candidates for BPA, especially after PTE, includes a complete re-assessment of the patient with persistent symptomatic PH after PTE at least four to six months after surgery using high quality imaging techniques such as computed tomography pulmonary angiography (CTPA), selective pulmonary angiography (to provide fine details) and right heart catheterization (RHC) to assess the hemodynamic impairment. However, these imaging techniques are not widely available and require expertise

EGFR-Targeted Antibody–Drug Conjugate to Different Aminobisphosphonates:Direct and Indirect Antitumor Effects on Colorectal Carcinoma Cells

Antibody––drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a “biological missile” that can destroy tumor cells while increasing the therapeutic index and decreasing toxicity. One of the most critical factors in ADC design is selecting a target antigen that is highly expressed on the surface of cancer cells. In this study, we conjugated Cetuximab (Cet), a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to aminobisphosphonates (N-BPs) such as ibandronate (IBA) or risedronate (RIS) or zoledronate (ZA). Cetuximab is administered to patients with metastatic colorectal carcinoma (mCRC) with a wild-type (WT) EGFR transduction pathway. Also, it is well established that N-BPs can trigger the antitumor activity of Vδ2 T cells in both in vitro and in vivo experimental models. The resulting ADCs were added in co-culture to assess the effect on CRC cell line proliferation and sensitivity to Vδ2 T antitumor lymphocytes in comparison with the native antibody. These assays have been performed both in conventional and 3D spheroid cultures. We found that all three ADCs can increase the inhibitory effect on cell proliferation of the WT-EGFR cell line Caco-2 while only Cet-RIS and Cet-ZA can increase the cytotoxicity mediated by Vδ2 T cells against both WT and EGFR-mutated CRC cell lines (Caco-2, DLD-1, and HCT-116). Also, the ADCs can trigger the cell proliferation of Vδ2 T cells present in peripheral blood and tumor specimens. Our findings indicate that anti-EGFR antibodies bound to N-BPs can improve the antitumor effects of the native antibody possibly increasing the therapeutic effect.</p