Painful oral aphthous-like lesions in patient with kidney cancer after target therapy and bisphosphonate administration: a case report of adverse drug reaction.

Aim. Tyrosine kinase inhibitors (TKIs) targeting tu- mor angiogenesis and mammalian target of rapamycin inhibitors (mTOR) are indicated for the management of several cancer types, as for renal cell carcinoma (RCC). Oral ulcerations are reported as common adverse drug reactions of mTOR inhibitors and are currently classified as mTOR inhibitor associated stomatitis (mIAS). Interestingly, these lesions appear as aphthous-like stoma- titis rather than the mucositis seen with chemotherapy agent. Case report. A 49 years old male patient underwent to the left radical nephrectomy in May 2014 for clear RCC. From July to October 2014 he was treated with Pazopanib, a tyrosine kinase inhibitor. In December 2014 the patient started the treatment with Zoledronic acid and Everolimus, an amino-bisphosphonates and an mTOR inhibitor, respectively. Everolimus administration was suspended on the 1st of January 2015 and resumed on the 4th of February. In February 2015, the patient referred to our department for acute pain of mouth floor and tongue; the onset of these symptoms was subse- quent to mTOR therapy. This pain compromised his oral functions (chewing, swallowing, phonetic) and quality of life. Intraoral examination showed aphthous-like lesions on both borders of the tongue and on the right side of the mouth floor. Local antiseptic (0.2% chlorhexidine rinse, twice daily for 1 week), 0.050 g clobetasol propionate cream (twice a day for 4 week, and one times a day for the following 4 weeks) and a wound-healing promoter (Mucosamin Spray®, twice a day for 2 weeks) were administered. Since the oncologist decided to not discontinue the target therapy, the patient continued local therapy until the end of the treatment with everolimus. After two weeks from the first visit, a complete healing of the oral mucosa was observed and the patient complained no pain. Conclusion. This case report confirms the recent view that target therapy with everolimus may induce the onset of aphthous-like stomatitis as adverse drug reaction. Therefore, diagnostic algorithms for stomatitis should include a careful drug history, emphasizing the focus also on oral adverse effects the new target cancer therapies

Leucocyte-and platelet-rich fibrin block: Its use for the treatment of a large cyst with implant-based rehabilitation

The management of critical-size bone defects is still demanding. Recently, autologous platelet concentrates in combination with bone substitute have been applied and reported in a few studies. Our aim is to report the healing of a critical-size alveolar bone defect treated with a new bone regeneration technique by means of L-PRF and L-PRF blocks. A 45-year-old woman presented a large cystic lesion; the extraction of three teeth, a cyst removal procedure, and bone regeneration procedures with L-PRF and L-PRF blocks were planned. The L-PRF block was prepared by mixing a bone substitute with a piece of L-PRF membrane and liquid fibrinogen. Additionally, after bone healing an implant-based rehabilitation was optimally performed. On the basis of the positive results, in terms of bone healing and tissue regeneration in a large bone defect, the application of LPRF and L-PRF blocks, in agreement with the scarce literature, is suggested as a feasible procedure in selected cases

Nanostructured 3C-SiC on Si by a network of (111) platelets: a fully textured film generated by intrinsic growth anisotropy

In this paper, we address the unique nature of fully textured, high surface-to-volume 3C-SiC films, as produced by intrinsic growth anisotropy, in turn generated by the high velocity of the stacking fault growth front in two-dimensional (111) platelets. Structural interpretation of high resolution scanning electron microscopy and transmission electron microscopy data is carried out for samples grown in a hot-wall low-pressure chemical vapour deposition reactor with trichlorosilane and ethylene precursors, under suitable deposition conditions. By correlating the morphology and the X-ray diffraction analysis we also point out that twinning along (111) planes is very frequent in such materials, which changes the free-platelet configuration

SNP genotyping elucidates the genetic diversity of Magna Graecia grapevine germplasm and its historical origin and dissemination

Background: Magna Graecia is the ancient name for the modern geopolitical region of South Italy extensively populated by Greek colonizers, shown by archeological and historical evidence to be the oldest wine growing region of Italy, crucial for the spread of specialized viticulture around Mediterranean shores. Here, the genetic diversity of Magna Graecia grape germplasm was assessed and its role in grapevine propagation around the Mediterranean basin was underlined. Results: A large collection of grapevines from Magna Graecia was compared with germplasm from Georgia to the Iberian Peninsula using the 18 K SNP array. A high level of genetic diversity of the analyzed germplasm was determined; clustering, structure analysis and DAPC (Discriminant Analysis of Principal Components) highlighted the genetic relationships among genotypes from South Italy and the Eastern Mediterranean (Greece). Gene flow from east (Georgia) to west (Iberian Peninsula) was identified throughout the large number of detected admixed samples. Pedigree analysis showed a complex and well-structured network of first degree relationships, where the cultivars from Magna Graecia were mainly involved. Conclusions: This study provided evidence that Magna Graecia germplasm was shaped by historical events that occurred in the area due to the robust link between South Italian and Greek genotypes, as well as, by the availability of different thermal resources for cultivars growing in such different winegrowing areas. The uniqueness of this ampelographic platform was mainly an outcome of complex natural or human-driven crosses involving elite cultivars

Moscato Cerletti, a rediscovered aromatic cultivar with oenological potential in warm and dry areas

Baron Antonio Mendola was devoted to the study of grapevine, applying ampelography and dabbling in crosses between cultivars in order to select new ones, of which Moscato Cerletti, obtained in 1869, was the most interesting. Grillo, one of the most important white cultivars in Sicily, was ascertained to be an offspring of Catarratto Comune and Zibibbo, the same parents which Mendola claimed he used to obtain Moscato Cerletti. Thus the hypothesis of synonymy between Moscato Cerletti and Grillo or the same parentage for both sets of parents needs to be verified. In the present study, historical documents were consulted and genetic analyses and ampelographic, agronomic and qualitative characterisation carried out to determine the distinctiveness of each cultivars. These were also compared with Catarratto Comune and Zibibbo in order to establish the Moscato Cerletti pedigree. Due to their different SSR profiles, Grillo and Moscato Cerletti were confirmed as two distinct cultivars; they also differed in ripening times and sugar storage ability, as well as in the aromatic grape produced by Moscato Cerletti only. The trio genotype genetic analysis confirmed that Zibibbo is a parent of Moscato Cerletti (justifying the aromatic grape), whilst the SSR profiles did not show Catarratto Comune to be a second parent. Moscato Cerletti was found to have oenological potential in the production of sparkling muscat wines due to its ability to adapt to a changing climate in warm and dry environments and in different winegrowing regions

A new intra-specific and high-resolution genetic map of eggplant based on a ril population, and location of QTLS related to plant anthocyanin pigmentation and seed vigour

Eggplant is the second most important solanaceous berry-producing crop after tomato. Despite mapping studies based on bi-parental progenies and GWAS approaches having been performed, an eggplant intraspecific high-resolution map is still lacking. We developed a RIL population from the intraspecific cross ‘305E40’, (androgenetic introgressed line carrying the locus Rfo-Sa1 conferring Fusarium resistance) x ‘67/3’ (breeding line whose genome sequence was recently released). One hundred and sixty-three RILs were genotyped by a genotype-by-sequencing (GBS) approach, which allowed us to identify 10,361 polymorphic sites. Overall, 267 Gb of sequencing data were generated and ~773 M Illumina paired end (PE) reads were mapped against the reference sequence. A new linkage map was developed, including 7249 SNPs assigned to the 12 chromosomes and spanning 2169.23 cM, with iaci@liberoan average distance of 0.4 cM between adjacent markers. This was used to elucidate the genetic bases of seven traits related to anthocyanin content in different organs recorded in three locations as well as seed vigor. Overall, from 7 to 17 QTLs (at least one major QTL) were identified for each trait. These results demonstrate that our newly developed map supplies valuable information for QTL fine mapping, candidate gene identification, and the development of molecular markers for marker assisted selection (MAS) of favorable alleles

Clinical validation of 13-Gene DNA methylation analysis from oral brushing: a non invasive sampling procedure for early detection of oral squamous cell carcinoma. A multicentric study

1. Introduction In a recent study our research group described a non-invasive sampling procedure based on DNA methylation analysis of a set of 13 genes with a high level of accuracy (sensitivity 96.6%, specificity 100%) in the detection of squamous cell carcinoma of the oral cavity (OSCC) [1]. The purpose of the present study was to test the diagnostic performance of this non invasive sampling procedure in an italian multicentric study. 2. Materials and Methods Oral brushing specimens were collected in ten different italian units of oral medicine. Each oral medicine unit collected blindly 10 brushing specimens from patients affected by OSCC and an equal number of age and sex-matched healthy controls. 13-gene DNA methylation analysis was performed and each sample was considered positive or negative in relation to a predefined cut-off value. 3. Results 181 out of 200 planned specimens were analyzed. DNA could not be amplified in 4 cases (2.2%). 86/93 (92.5%) specimens derived from OSCC patients were detected as positive and 70/84 (83.3%) specimens derived from healthy donors showed a negative score. 4. Conclusions Data from multicentric study confirmed a high level of sensitivity of our procedure whereas level of specificity is slightly lower if compared to our previous study. These data suggest that our procedure may be proposed as a first level diagnostic test with the aim to avoid a diagnostic delay in Oral Squamous Cell Carcinoma. Conflicts of Interest: As a possible conflict of interest, L. Morandi and D.B.G. submitted a patent (the applicant is the University of Bologna) in November 2016 to the National Institute of 398 Industrial Property; however, we believe that this is a natural step of translational research (bench-to-bedside) 399 and guarantee that the scientific results are true. The remaining authors declare that they have no competing 400 interest

Role of novel targeted therapies in the clinic

The number and variety of novel, molecular-targeted agents offers realistic hope for significant advances in cancer treatment. The potential of these new treatment approaches is unquestionable, but the reality is something that only thorough clinical evaluation and experience can reveal. Clinical experience of targeted therapies is at an early stage but it is likely that we will have an increasing number of treatment options available to us in the near future. This manuscript explores our current understanding of molecular-targeted therapies and considers: What approach should be used? (single vs multitarget agents); When should they be administered? (identifying the optimal point for intervention); How should they be used? (monotherapy or combination therapy regimens); and Who should we be giving them to? (acknowledging the need for patient selection)

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060