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The improvement of the mucosal sealing around the implant represents a challenge, one that prompted research into novel materials. To this purpose, a printable poly(ε-caprolactone) (PCL)-based composite loaded with alumina-toughened zirconia (ATZ) at increasing rates of 10, 20, and 40 wt.% was prepared, using a solvent casting method with chloroform. Disks were produced by 3D printing; surface roughness, free energy and optical contact angle were measured. Oral fibroblasts (PF) and epithelial cell (SG) tests were utilized to determine the biocompatibility of the materials through cell viability assay and adhesion and spreading evaluations. The highest level of ATZ resulted in an increase in the average roughness (S a ), while the maximum height (S z ) was higher for all composites than that of the unmixed PCL, regardless of their ATZ content. Surface free energy was significantly lower on PCL/ATZ 80/20 and PCL/ATZ 60/40, compared to PCL and PCL/ATZ 90/10. The contact angle was inversely related to the quantity of ATZ in the material. PF grew without variations among the different specimens at 1 and 3 days. After 7 days, PF grew significantly less on PCL/ATZ 60/40 and PCL/ATZ 80/20 compared to unmixed PCL and PCL 90/10. Conversely, ATZ affected and improved the growth of SG. By increasing the filler amount, PF cell adhesion and spreading augmented, while PCL/ATZ 80/20 was the best for SG adhesion. Overall, PCL/ATZ 80/20 emerged as the best composite for both cell types; hence, it is a promising candidate for the manufacture of custom made transmucosal dental implant components.

Cadmium (Cd) toxicity poses a significant threat to human health and the environment due to its widespread occurrence and persistence. In recent years, considerable attention has been directed towards exploring natural compounds with potential protective effects against Cd-induced toxicity. Among these compounds, resveratrol (RV) has emerged as a promising candidate, demonstrating a range of beneficial effects attributed to its antioxidant and anti-inflammatory properties. This literature review systematically evaluates the protective role of RV against Cd toxicity, considering the various mechanisms of action involved. A comprehensive analysis of both in vitro and in vivo studies is conducted to provide a comprehensive understanding of RV efficacy in mitigating Cd-induced damage. Additionally, this review highlights the importance of phytoremediation strategies in addressing Cd contamination, emphasizing the potential of RV in enhancing the efficiency of such remediation techniques. Through the integration of diverse research findings, this review underscores the therapeutic potential of RV in combating Cd toxicity and underscores the need for further investigation to elucidate its precise mechanisms of action and optimize its application in environmental and clinical settings.

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 ( p < 0.001), while IL-12 showed a direct relationship with CAL gain ( p = 0.005) and PPD reduction ( p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.

Background and Objectives : Sexual violence (SV) is a major global public health concern. While socioeconomic factors and familial relationships have been widely reported to contribute to SV, the role of alcohol consumption should not be ignored. Indeed, alcohol can impair cognition, distort reality, increase aggression, and ease drug-facilitated sexual assault. This retrospective study aims to explore the relationship between alcohol consumption and SV by examining the prevalence, characteristics, and consequences of violence episodes. Materials and Methods : A total of 1481 women accessed the Rape Centre "Centro Soccorso Violenza Sessuale" in Turin, Italy between 2008 and 2019, with 223 reporting alcohol consumption before the assault. Results : The alcohol group had a younger age profile, predominantly within the 18-25-year-old category. SV incidents involving alcohol consumers were more likely to occur in public places or in someone else's home, while the non-alcohol-consuming group experienced more violence in their own homes. Acquaintances and unknown individuals were primarily responsible, whereas partners were the most common perpetrators of violence against non-alcohol-consuming women. Alcohol consumers sought medical attention sooner after the assault and exhibited more symptoms and injuries, particularly of neurological origin. Concurrent use of recreational drugs was higher among alcohol consumers. The logistic regression analysis revealed higher odds of injury for Italian women and those in the 18-35 age groups after consuming alcohol. Conclusions : This study contributes to the understanding of the relationship between alcohol consumption and SV. The prevalence of alcohol-related sexual aggression is lower compared to that shown in previous studies. Nationality, age, and assailant identity influence SV dynamics. These findings can guide well-targeted interventions and prevention strategies to address SV and inform communities facing similar challenges.

Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed as having periodontally healthy conditions (H), severe periodontitis (P), and healthy but reduced periodontium after active periodontal treatment (T) were consecutively enrolled (15 per each group) in the study. A higher number of spots were identified in the proteome of unstimulated whole saliva collected from H and T subjects compared with P group, mainly within the range of 8-40 kDa. Protein spots of interest were analysed by MALDI-TOF-MS, allowing the identification of cystatin SN (CST1) isoform, as confirmed by Western blot. CST1 was markedly expressed in the H group, while it was absent in most P samples ( p < 0.001). Interestingly, a distinct CST1 expression was observed in saliva from T patients. CST1 was negatively correlated with the percentage of pathological sites ( p < 0.001) and was effective in discriminating active periodontitis from healthy periodontal status (whether H or T). Therefore, salivary CST1 may be a promising non-invasive biomarker for periodontal disease diagnosis and monitoring.

Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy is due to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake and lower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinical applications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism of action on muscle and its effect on muscle performance are unclear. We investigated the effects of Met combined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks while undergoing daily moderate exercise. We evaluated the following: PP through graded endurance exercise test performed before the beginning of the training protocol and 48 h before the end of the training period; blood ALT, AST, LDH and CK-MB levels in order to address muscle damage; and several blood and muscle myokines and the expression of factors believed to be involved in muscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effects of exercise on performance, although it protects myocytes from exercise-induced damage. Moreover, given that Met positively affects exercise-induced muscle adaptation, our data support the idea of the therapeutic application of Met when muscle function and structure are compromised.

The serendipitous discovery of nanobodies (NBs) around two decades ago opened the door to new possibilities for innovative strategies, particularly in cancer treatment. These antigen-binding fragments are derived from heavy-chain-only antibodies naturally found in the serum of camelids and sharks. NBs are an appealing agent for the progress of innovative therapeutic strategies because they combine the advantageous assets of smaller molecules and conventional monoclonal antibodies (mAbs). Moreover, the possibility to produce NBs using bacterial systems reduces manufacturing expenses and speeds up the production process, making them a feasible option for the development of new bio-drugs. Several NBs have been developed over the past 10 years and are currently being tested in clinical trials for various human targets. Here, we provide an overview of the notable structural and biochemical characteristics of NBs, particularly in their application against HER2, an extracellular receptor that often gets aberrantly activated during breast cancer tumorigenesis. The focus is on the recent advancements in diagnostic and therapeutic research up to the present date., Competing Interests: The authors declare no conflict of interest.

A cross-sectional study was conducted that describes the characteristics of sexual violence episodes related to the intake of alcohol and drugs observed among women that turned to the "Centro Soccorso Violenza Sessuale" (SVS) of the Sant'Anna Hospital in Turin between 1 January 2008, and 31 December 2017. Two hundred twenty-two patients were enrolled, 25 of which were minors, 141 were Italians, and most of them knew their aggressor and were raped in a private home. One hundred and fifty-five of them declared to the healthcare personnel to have taken alcoholic substances and/or drugs in conjunction with the event (86 reported having drunk alcohol, 36 having taken drugs and 33 disclosed both alcohol and drug abuse). If the woman knew her abuser, alcohol consumption was described as voluntary in more than 80% of cases, while in relation to drugs the consumption was equally voluntary or fraudulent. About 73% of women who reported having drunk alcohol just had amnesia or amnesia related to other symptoms, while amnesia was present in about 63% of women who reported only drug use. Physicians observed physical injuries on 156 women. Patients who reported to have assumed alcohol presented a significantly higher risk to suffer any physical injury and have a significantly increased risk to suffer injuries to their head and/or neck. The results obtained underline how even in Northern Italy alcohol intake represents the most widespread psychoactive substance in case of drug-facilitated sexual assault. There is therefore a need to promote education and prevention campaigns among citizens, especially among the youngest.

Although increasing evidence is emerging on the contribution of chemical elements in periodontal health, no studies have concomitantly evaluated the ionic profile in gingival crevicular fluid (GCF) and saliva in relation to the underlying periodontal status. Our hypothesis is that these biofluids have distinctive ionic content. Therefore, the aim of this cross-sectional study was to analyze the elemental composition of GCF and saliva in order to explore which biological matrix and which combination of elements could discriminate between periodontitis and periodontal health. Twelve ions were analyzed in GCF and unstimulated saliva from 54 subjects (18 periodontally healthy, 18 untreated severe periodontitis and 18 treated severe periodontitis) using inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). These analytical techniques were able to determine levels of sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg), while the other elements were below the detection threshold. Na and K ions were detected at elevated concentration in untreated periodontitis compared with treated periodontitis and healthy periodontium. Ca was increased in untreated periodontitis, but the difference was not significant. In saliva, only Na was significantly associated with periodontitis. The combination of Na and K in GCF enabled the correct assignment of a subject to the periodontitis or healthy group. Based on these preliminary results, GCF demonstrated higher clustering potential than saliva.

We investigated the role of PI3Kγ in oral carcinogenesis by using a murine model of oral squamous carcinoma generated by exposure to 4-nitroquinoline 1-oxide (4NQO) and the continuous human cancer cell line HSC-2 and Cal-27. PI3Kγ knockout (not expressing PI3Kγ), PI3Kγ kinase-dead (carrying a mutation in the PI3Kγ gene causing loss of kinase activity) and wild-type (WT) C57Bl/6 mice were administered 4NQO via drinking water to induce oral carcinomas. At sacrifice, lesions were histologically examined and stained for prognostic tumoral markers (EGFR, Neu, cKit, Ki67) and inflammatory infiltrate (CD3, CD4, CD8, CD19 and CD68). Prevalence and incidence of preneoplastic and exophytic lesions were significantly and similarly delayed in both transgenic mice versus the control. The expression of prognostic markers, as well as CD19 + and CD68 + cells, was higher in WT, while T lymphocytes were more abundant in tongues isolated from transgenic mice. HSC-2 and Cal-27 cells were cultured in the presence of the specific PI3Kγ-inhibitor (IPI-549) which significantly impaired cell vitality in a dose-dependent manner, as shown by the MTT test. Here, we highlighted two different mechanisms, namely the modulation of the tumor-infiltrating cells and the direct inhibition of cancer-cell proliferation, which might impair oral cancerogenesis in the absence/inhibition of PI3Kγ.

The purpose of this randomized controlled study was to evaluate the clinical efficacy of a novel oral spray containing resveratrol (RV) in controlling bacterial biofilm and gingival inflammation in early childhood. RV, a natural polyphenol, known for its anti-inflammatory and anti-infective activities, was included in a nanovector of 2-hydroxypropyl-beta-cyclodextrins (HPβCD) to improve its bioavailability. A total of 64 children between two and five years of age with plaque-induced gingivitis were randomly included in two equal groups. Both groups were enrolled in a mechanical plaque control program for a period of four weeks, while the test group was also instructed to use the RV-HPβCD mouthwash (in spray formulation) once daily, after toothbrushing. All children underwent three oral hygiene motivation sessions, 14 days apart, during which the full-mouth presence of bacterial plaque, gingival inflammation, dental stain and salivary pH were recorded. At two-week appointment, they also received professional plaque removal. The use of RV-based oral spray significantly reduced the amount of dental plaque and the percentage of bleeding sites and improved salivary pH compared to the control group at both two- and four-week examinations. Based on these promising results, the local delivery of RV-HPβCD via oral spray could enhance the control of dental biofilm in early childhood, when antiseptic mouthwashes are not recommended.

This study assessed the periodontal conditions of type 2 diabetes (T2DM) patients attending an Outpatient Center in North Italy and explored the associations between metabolic control and periodontitis. Periodontal health of 104 T2DM patients (61 men and 43 women, mean age of 65.3 ± 10.1 years) was assessed according to CDC/AAP periodontitis case definitions and Periodontal Inflamed Surface Area (PISA) Index. Data on sociodemographic factors, lifestyle behaviors, laboratory tests, and glycated hemoglobin (HbA1c) levels were collected by interview and medical records. Poor glycemic control (HbA1c ≥ 7%), family history of T2DM, and C-reactive protein levels were predictors of severe periodontitis. An increase in HbA1c of 1% was associated with a rise in PISA of 89.6 mm 2 . On the other hand, predictors of poor glycemic control were severe periodontitis, waist circumference, unbalanced diet, and sedentary lifestyle. A rise in PISA of 10 mm 2 increased the odds of having HbA1c ≥ 7% by 2%. There is a strong bidirectional connection between periodontitis and poor glycemic control. The inflammatory burden posed by periodontitis represents the strongest predictor of poor glycemic control.

Pattern analysis of the salivary metabolic profile has been proven accurate in discriminating between generalized periodontitis (GP) patients and healthy individuals (HI), as this disease modifies the salivary concentrations of specific metabolites. Due to the scarcity of data from previous studies, this study aimed to evaluate if non-surgical periodontal therapy (NST) could affect the metabolomic profile in GP patients' saliva and if it compares to that of HI. Unstimulated salivary samples were collected from 11 HI and 12 GP patients before and 3 months after NST. Nuclear Magnetic Resonance (NMR) spectroscopy, followed by a supervised multivariate statistical approach on entire saliva spectra and partial least square (PLS) discriminant analysis, were performed to obtain metabolic profiles. In the GP group, periodontal treatment improved all clinical parameters, but not all the diseased sites were eradicated. PLS revealed an accuracy of 100% in distinguishing between metabolic profiles of GP patients before and after NST. Orthogonal projection to latent structure was able to discriminate between the three groups of subjects with an accuracy of 85.6%. However, the post-NST metabolic profile of GP patients could not be completely assimilated to that of HI. Although NST may produce significant changes in the metabolic profile, GP patients maintained a distinctive fingerprint compared to HI., Competing Interests: The authors declare no conflict of interest.

Clinical criteria are inappropriate to measure the degree of susceptibility to progression of periodontal damage. Thus, the aim of this study was to assess whether gingival crevicular fluid (GCF) levels of cytokines could discriminate patients suffering from stage III periodontitis with moderate (Grade B) and rapid rates of progression (Grade C) prior to and 6 months after non-surgical periodontal treatment. GCF samples were obtained from moderate and deep sites of 20 patients diagnosed as Grade B and 20 patients as grade C stage III periodontitis and analyzed for interleukin (IL)-1β, IL-9, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) using a high-sensitivity Bio-Plex Suspension Array System. At baseline, higher IL-1β but lower IL-9 GCF levels were observed in moderate sites of the grade C compared to the grade B group. In spite of comparable clinical improvement, this difference maintained after treatment, suggesting a residual pro-inflammatory state. In deep sites, no differences were observed between periodontitis groups except for VEGF levels that decreased more in Grade B periodontitis at 6 months post-therapy. A mathematical model was constructed to identify Grade C periodontitis patients based on the subjects' GCF levels of IL-1β and IL-9, which achieved an area under the receiver-operating characteristic (ROC) curve of 0.94. This study can contribute to the early assessment of risk of future breakdown in periodontitis patients.

Over the past decade, there has been growing interest in the association between macro and trace minerals in body fluids and systemic diseases related to chronic inflammation and oxidative stress. Due to the paucity of data in the literature on periodontitis, the aim of this cross-sectional study was to assess the relationship between mineral elements in saliva and periodontal status in patients with untreated and treated periodontitis compared to periodontally healthy controls. Salivary samples from 66 nonsmoker healthy patients (20 periodontally healthy, 24 untreated severe periodontitis and 22 treated severe periodontitis) were analyzed by using inductively coupled plasma mass-spectrometry (ICP-MS). Significant increases in copper (Cu), sodium (Na), iron (Fe) and manganese (Mn) concentrations occurred in saliva of severe periodontitis subjects compared to periodontally healthy controls. No differences were detected between healthy controls and treated periodontitis patients apart from levels of zinc (Zn) and lithium (Li) that were found to be increased and reduced, respectively, in periodontitis group. Most subjects were correctly separated by cluster analysis into active periodontitis and periodontally healthy individuals. Treated periodontitis individuals were classified as healthy subjects. Based on these preliminary results, the assessment of salivary concentration of mineral elements might be useful in discriminating periodontal health and disease.

Background: Data about acute poisoning in Italian pediatric patients are obsolete or absent. This study would partially fill this exiting gap and compare the scene with others around the world., Methods: A retrospective evaluation was performed on a 2012-2017 data registry of the Children's Emergency Department at the Regina Margherita Hospital of Turin, where 1030 children under age 14 were accepted with a diagnosis of acute intoxication., Results: The median age of the patients was 2.2 years (IQR 2.3) and 55% were male. Events occurred mostly in children aged 1-4 years (n = 751, 72.9%). Six hundred and eight patients (59%) were exposed to Nonpharmaceutical agents, the household cleaning products being the more frequent (n = 298, 49%). Exposure to Pharmaceuticals were 422 (41%); the most common Pharmaceuticals were analgesics (n = 88, 20.8%), psychotropics (n = 77, 18.2%) and cardiovascular (n = 53, 12.6%) drugs. The 85% of the intoxications occurred accidentally, the 10.6% as therapeutic error, the 2.3% as suicide attempts and the 1.5% for recreational purposes. No patient died., Conclusions: Despite acute poisoning being a relevant problem in pediatric emergency, our results would seem to paint a less worrying picture if compared to other countries, mainly when considering the children hospitalized in the pediatric intensive care unit and the number of deaths. Nevertheless, our study might represent a tool for public health authorities to program incisive interventions.

We generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34+ cells and differentiated them into functional endothelial cells (ECs) secreting factor VIII (FVIII) for gene and cell therapy approaches to cure hemophilia A (HA), an X-linked bleeding disorder caused by F8 mutations. iPSCs were transduced with a lentiviral vector carrying FVIII transgene driven by an endothelial-specific promoter (VEC) and differentiated into bona fide ECs using an optimized protocol. FVIII-expressing ECs were intraportally transplanted in monocrotaline-conditioned non-obese diabetic (NOD) severe combined immune-deficient (scid)-IL2rγ null HA mice generating a chimeric liver with functional human ECs. Transplanted cells engrafted and proliferated in the liver along sinusoids, in the long term showed stable therapeutic FVIII activity (6%). These results demonstrate that the hemophilic phenotype can be rescued by transplantation of ECs derived from HA FVIII-corrected iPSCs, confirming the feasibility of cell-reprogramming strategy in patient-derived cells as an approach for HA gene and cell therapy., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Oral squamous cell carcinoma (OSCC) diagnoses in elderly patients are expected to double in the next 20 years. Current guidelines suggest surgery as a preferred approach, but elderly patients are hardly considered suitable to challenging surgical treatments. Using a multi-centric retrospective analysis, we evaluated the outcomes of 99 patients affected by OSCC and aged at least 70, who underwent to either transoral procedures (TP), open neck resection without (OR) or with reconstruction (ORR). In our cohort, overall survival was significantly hampered by concomitant diseases and postsurgical complications, whose development is driven by the former. Thus, our findings support the growing acceptance that chronological age alone should not be a sufficient contraindication for aggressive surgery in the treatment of OSCC. However, elderly patients affected by OSCC are undoubtedly delicate surgical candidates and accurate selection prior to surgery with curative intent is mandatory., (Copyright © 2018 Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.)

Avenanthramides (Avns), polyphenols found exclusively in oats, are emerging as promising therapeutic candidates for the treatment of several human diseases, including colon cancer. By engineering a Saccharomyces cerevisiae strain, we previously produced two novel phenolic compounds, N -( E )- p -coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, YAvnI) and N -( E )-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, YAvnII), which are endowed with a structural similarity to bioactive oat avenanthramides and stronger antioxidant properties. In this study, we evaluated the ability of these yeast-derived recombinant avenanthramides to inhibit major hallmarks of colon cancer cells, including sustained proliferation, migration and epithelial-mesenchymal transition (EMT). Using the human colon adenocarcinoma cell line HT29, we compared the impact of YAvns and natural Avns, including Avn-A and Avn-C, on colon cancer cells by performing MTT, clonogenic, adhesion, migration, and anchorage-independent growth assays, and analyzing the expression of EMT markers. We found that both YAvns and Avns were able to inhibit colon cancer cell growth by increasing the expression of p21, p27 and p53 proteins. However, YAvns resulted more effective than natural compounds in inhibiting cancer cell migration and reverting major molecular features of the EMT process, including the down-regulation of E-cadherin mRNA and protein levels.

Oxidative stress exerts major role in the pathogenesis of side effects of many antineoplastic drugs, including ototoxicity of cisplatin. In particular, increased levels of reactive oxygen species (ROS) represent one of the molecular mechanisms underlying the apoptosis of different types of hearing cells. Antioxidants and ROS scavengers may thus represent potential therapeutic options to prevent platinum-associated ototoxicity. The aim of this preliminary case-control study was to explore the efficacy of a dietary antioxidant supplement, in order to hamper the occurrences of ototoxicity in patients undergoing cisplatin chemotherapy. As results, a significant protection against cochlear toxic damage was demonstrated in patients who took the antioxidant supplement, which furthermore prevented the occurrence of hearing disorders and tinnitus. These clinical evidences were corroborated by the oxidative status of patients. After cisplatin chemotherapy, the plasma derivatives of reactive oxygen metabolites (d-ROMs) content rapidly increased in control patients, but it was maintained in those under dietary supplementation, likely because of a higher anti-ROMs potential. Indeed, an increment in rapid anti-ROMs was detected in supplemented patients, though no differences were highlighted in terms of slow anti-ROMs. In conclusion, in this preliminary report we demonstrated the feasibility of a dietary antioxidant supplementation in order to prevent the cisplatin induced hearing damage.

Background: Generic anticancer drugs represent an opportunity in terms of cost savings but there are some concerns about their tolerability. The safety profiles of generic versus branded oxaliplatin formulations have never been studied in detail., Patients and Methods: We tested in vitro concentrations, stability and efficacy of branded versus generic oxaliplatin formulations, then we retrospectively collected data about hypersensitivity reactions (HSR) of 427 colorectal cancer patients treated with oxaliplatin-based regimens., Results: No significant difference in oxaliplatin concentration or time-dependent antiproliferative activity between branded and generic oxaliplatin was detected. The incidence of HSR was 12.1% (33/273 patients) in those treated with branded and 9.8% (15/154 patients) in those treated with generic oxaliplatin (p=0.46). The occurrence of grade III-IV HSRs and severe HSRs leading to oxaliplatin discontinuation were comparable., Conclusion: No difference between generic and branded formulations of oxaliplatin were demonstrated in preclinical nor in clinical settings. Generic oxaliplatin can be considered a safe alternative to branded formulation., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Older patients are not considered good candidates to undergo more challenging therapeutic treatments, e.g. highly invasive surgery and complex chemotherapy. However, their exclusion from standard therapeutic options is not justifiable. Herein, we reviewed 212 patients aged ≥ 70, affected with laryngeal squamous cell carcinoma, and treated with transoral laser microsurgery or open neck (partial / total) laryngectomy with radical intent. The main aim was to compare patient outcomes to identify predictive factors that can be used by surgeons to choose the most appropriate treatment option. In our cohort, patients affected with more advanced tumour and hence treated by invasive open neck surgeries (above all TL) are more prone to develop complications and undergo fatal outcome than those with early disease treated by laser microsurgery, independently of age at surgery. In conclusion, elderly patients affected by laryngeal cancer can be treated similarly to younger patients, keeping in mind that more invasive surgeries are associated with a higher risk of developing complications. The advantages of mini-invasive surgery make it a possible first choice treatment in very old and frail patients suffering from laryngeal cancer, especially considering the recent success in treatment of some advanced stage tumours. Furthermore, comorbidities, by themselves, should not be used as exclusion criteria for subjecting an elderly patient to a different treatment that is from standard therapy., (© Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.)

In a transgenic mice (BALB-neuT) over-expressing ErbB2 receptor, we investigated the adult mouse median nerve in physiological and pathological conditions. Results showed that, in physiological conditions, the grip function controlled by the median nerve in BALB-neuT mice was similar to wild-type (BALB/c). Stereological assessment of ErbB2-overexpressing intact nerves revealed no difference in number and size of myelinated fibers compared to wild-type mice. By contrast, after a nerve crush injury, the motor recovery was significantly faster in BALB-neuT compared to BALB/c mice. Moreover, stereological assessment revealed a significant higher number of regenerated myelinated fibers with a thinner axon and fiber diameter and myelin thickness in BALB-neuT mice. At day-2 post-injury, the level of the mRNAs coding for all the ErbB receptors and for the transmembrane (type III) Neuregulin 1 (NRG1) isoforms significantly decreased in both BALB/c and BALB-neuT mice, as shown by quantitative real time PCR. On the other hand, the level of the mRNAs coding for soluble NRG1 isoforms (type I/II, alpha and beta) increased at the same post-traumatic time point though, intriguingly, this response was significantly higher in BALB-neuT mice with respect to BALB/c mice. Altogether, these results suggest that constitutive ErbB2 receptor over-expression does not influence the physiological development of peripheral nerves, while it improves nerve regeneration following traumatic injury, possibly through the up-regulation of soluble NRG1 isoforms.

Vaccines against oncoantigens halt early neoplastic lesions in several cancer-prone, genetically engineered mouse models, whereas their ability to prevent chemical carcinogenesis has not been explored. This is a significant issue, as exposure to chemical mutagens is responsible for a substantial percentage of cancers worldwide. Here, we show that the archetypal oncoantigen ERBB2 is transiently overexpressed in Syrian hamsters during the early stages of 7,12-dimethylbenz[α]anthracene (DMBA)-induced oral carcinogenesis. Repeated DNA vaccinations against ERBB2 significantly reduce the number, size, and severity of oral lesions in a manner directly proportional to the anti-ERBB2 antibody response. These results support the prospects of vaccines as a fresh strategy in the management of individuals at risk for exposure to defined carcinogenic agents.

We studied whether apelin-13 is cardioprotective against ischemia/reperfusion injury if given as either a pre- or postconditioning mimetic and whether the improved postischemic mechanical recovery induced by apelin-13 depends only on the reduced infarct size or also on a recovery of function of the viable myocardium. We also studied whether nitric oxide (NO) is involved in apelin-induced protection and whether the reported ischemia-induced overexpression of the apelin receptor (APJ) plays a role in cardioprotection. Langendorff-perfused rat hearts underwent 30 min of global ischemia and 120 min of reperfusion. Left ventricular pressure was recorded. Infarct size and lactate dehydrogenase release were determined to evaluate the severity of myocardial injury. Apelin-13 was infused at 0.5 μM concentration for 20 min either before ischemia or in early reperfusion, without and with NO synthase inhibition by N(G)-nitro-l-arginine (l-NNA). In additional experiments, before ischemia also 1 μM apelin-13 was tested. APJ protein level was measured before and after ischemia. Whereas before ischemia apelin-13 (0.5 and 1.0 μM) was ineffective, after ischemia it reduced infarct size from 54 ± 2% to 26 ± 4% of risk area (P < 0.001) and limited the postischemic myocardial contracture (P < 0.001). l-NNA alone increased postischemic myocardial contracture. This increase was attenuated by apelin-13, which, however, was unable to reduce infarct size. Ischemia increased APJ protein level after 15-min perfusion, i.e., after most of reperfusion injury has occurred. Apelin-13 protects the heart only if given after ischemia. In this protection NO plays an important role. Apelin-13 efficiency as postconditioning mimetic cannot be explained by the increased APJ level.

This paper illustrates the efficacy of DNA vaccination through electroporation in the prevention of oral transplantable carcinoma in Syrian hamsters. At 21 and 7 days before tumour challenge, 19 hamsters were vaccinated with plasmids coding for the extracellular and transmembrane domains of rat HER-2 receptor (EC-TM plasmids), whereas 19 control hamsters were injected intramuscularly with the empty plasmid. Immediately following plasmid injection, hamsters of both groups received two square-wave 25 ms, 375 V cm(-1) electric pulses via two electrodes placed on the skin of the injection area. At day 0, all hamsters were challenged in the submucosa of the right cheek pouch with HER-2-positive HCPC I cells established in vitro from an 7,12-dimethylbenz[a]anthracene-induced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) vaccinated hamsters. In addition, the vaccinated hamsters displayed both a stronger proliferative and cytotoxic response than the controls and a significant anti-HER-2 antibody response. Most of the hamsters that rejected the challenge displayed the highest antibody titres. These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.

Chemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette-Guerin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.