Human osteoblast-like cell adhesion on titanium substrates covalently functionalized with synthetic peptides

Biomaterials to be used for the production of endosseous devices in dental, orthopedic and maxillo-facial applications, might be designed to support, guide and enhance osteoblast adhesion. Cell recruitment onto biomaterial surface is a fundamental step within the complex process responsible for implant osseointegration; this process involves several proteins from the extra cellular matrix (ECM), cytoskeleton and cell membrane. A new strategy to improve endosseous implant integration is based on preparing biomimetic surfaces able to present adhesive factors to cells. Osteoblast adhesion takes place by at least two different mechanisms: the most investigated one implies the interaction with RGD sequences via cell-membrane integrin receptors; a further mechanism concerns the interaction between cell-membrane heparan sulfate proteoglycans and heparin-binding sites of ECM proteins. In the present study two different biomimetic surfaces were obtained by covalently grafting two adhesive peptides on oxidized titanium substrates after silanization: an RGD-containing peptide and a peptide mapped on human vitronectin. The two sequences are known to act via different adhesive mechanisms. The amount of human osteoblasts adhered onto peptide-enriched or not enriched titanium oxidized surfaces and the strength of cell binding were estimated, thus comparing the capacity of the bioactive substrates in promoting cell adhesion.     

Tumor-released microvesicles as vehicles of immunosuppression

Tumor-released microvesicles, or exosomes, which are abundant in the body fluids of patients with cancer, are likely to be involved in tumor progression. We recently showed that microvesicles released by human melanoma and colorectal carcinoma cells can promote the differentiation of monocytes to myeloid-derived suppressor cells which support tumoral growth and immune escape. These findings underscore an important role for these extracellular organelles in remodeling tumor-stromal interactions to promote malignancy.     

Coffee and tea consumption and risk of hepatocellular carcinoma in Italy

The role of coffee in the aetiology of hepatocellular carcinoma has raised great interest. In Italy, coffee consumption is high, thus allowing the investigation of the topic over a broad range of consumption. A hospital-based case-control study was conducted in Italy in 1999-2002, including 185 incidents, histologically confirmed cases of hepatocellular carcinoma aged 43-84 years. Controls were 412 subjects admitted to the same hospitals' networks for acute, non-neoplastic diseases unrelated to diet. Coffee and tea consumption were assessed using a validated food-frequency questionnaire. Odds ratios (ORs) and corresponding the 95% confidence intervals (CI) were computed using unconditional multiple logistic regression, adjusting for hepatitis viruses seropositivity, alcohol intake, smoking habits and other potential confounding factors. Compared to people who drunk <14 cups/week of coffee, the risk of hepatocellular carcinoma decreased for increasing levels of consumption (OR=0.4, 95% CI: 0.2-1.1 for >or=28 cups/week, p for trend = 0.02). In the present study, inverse relations were observed across strata of hepatitis C and, B virus infections and alcohol drinking. No significant association emerged with consumption of decaffeinated coffee (OR=0.7, 95% CI=0.2-2.5) or tea (OR=1.4, 95% CI=0.8-2.7). The present study supports the hypothesis of a favourable effect of coffee, though not decaffeinated coffee and tea, on the risk on hepatocellular carcinoma.     

Detection of mutated BRAFV600E variant in circulating DNA of stage III-IV melanoma patients

BRAFV600E is the most represented somatic point mutation in cutaneous melanoma, thus providing a unique molecular marker for this disease. The development of efficient methods for its detection in free circulating DNA of patients may lead to the improvement of diagnostic and prognostic tools. With this aim, we evaluated whether BRAFV600E represents a detectable marker in the plasma/serum from melanoma patients in a pilot study. Circulating cell-free DNA was extracted from the serum or plasma of 15 healthy donors and 41 melanoma patients at different clinical stages and obtained either presurgery or after surgery during follow-up. Quantitative analysis showed higher levels of circulating free DNA in patients compared to controls, with the highest levels detected in samples obtained presurgery and at stage IV. Four different PCR methods were compared for their capacity to amplify a few copies of BRAFV600E in wild-type DNA. BRAFV600E was detectable in circulating DNA of 12 patients and in none of the controls; only 1 PCR method reproducibly amplified BRAFV600E. Positive samples were obtained from 8/13 patients at stage IV and from 4/24 patients at stage III, but not in 4 patients at stage I-II; half of the positives were obtained presurgery and half at follow-up. Correspondence between circulating DNA and related tumors were examined for 20 patients, and a correlation was found for stage IV patients. In conclusion, this method can be utilized for monitoring the disease in stage IV melanoma patients but it appears unsatisfactory for the early detection of melanoma.     

A mathematical model for the evaluation of amplitude of hemoglobin fluctuations in elderly anemic patients affected by myelodysplastic syndromes: correlation with quality of life and fatigue

Therapy with RBC transfusions and rHuEPO for management of anemia in patients with myelodysplastic syndromes causes recurrent fluctuations in hemoglobin levels. The purpose of this study was to elaborate a mathematical model for the interpretation of hemoglobin fluctuations and to correlate the resulting numerical parameter (Variaglobin Index) with quality of life and fatigue. In 32 myelodysplastic patients, lower amplitude of the Variaglobin Index was found significantly correlated with a better quality of life and less fatigue. The mathematical model proposed here makes it easy to monitor anemia in myelodysplastic patients and to adjust therapy accordingly.     

Brain radiotherapy during treatment with anticonvulsant therapy as a trigger for toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous syndrome that can be occasionally caused by anticonvulsant drugs. In some cases, cranial irradiation may act as a precipitating factor. Thus, in cancer patients who suffer from brain metastases and are administered antiepileptic drugs for seizure prophylaxis, the risk of developing TEN after receiving palliative brain radiotherapy cannot be ignored. We is reported. The case of a young patient with non-small cell lung cancer (NSCLC) treated with prophylactic phenobarbital who developed TEN within a few days of completing cranial radiotherapy for brain metastases is reported. To minimize the risk of TEN in patients undergoing brain radiotherapy, prophylactic anticonvulsant therapy is recommended only after an accurate measurement of the true benefits. Alternatively, discontinuation of antiepileptic treatment before the initiation of brain radiotherapy, or the use of anticonvulsants associated with a lower risk of developing cutaneous reactions might be considered.     

Reduced expression of CDKN2a/p16INK4a in mycosis fungoides

Abstract Alterations in the CDKN2a gene have been demonstrated in a wide range of human tumors including hematopoietic malignancies. To verify whether altered CDKN2a expression is involved in the pathogenesis of mycosis fungoides (MF), we examined mRNA expression in 20 patients with MF by RT-PCR and dot blot hybridization. CDKN2a mRNA expression was undetectable in 5 of the 20 patients (25%), intermediate in 13 (65%) and high in 2 (10%). Immunohistochemical studies, which were performed in ten patients, revealed that in the four patients showing no mRNA, p16^INK4a was expressed in < 1% of neoplastic lymphocytes whereas in the four patients with an intermediate mRNA level, specific nuclear staining was present in 1–25% of tumor cells. In the two patients with high levels of CDKN2a mRNA, > 25% of neoplastic lymphocytes stained positively. No direct correlation between clinicopathological and molecular findings was evident in our patients. DNA mutational analysis revealed no alterations in a total of six patients examined. Our results indicate that the lack of CDKN2a expression, as found in 25% of the patients, may have a pathogenetic role in MF even though the absence of CDKN2a mRNA was not associated with point mutations or minor gene deletions. Received: 6 August 1998 / Received after revision: 21 October 1998 / Accepted: 2 November 1998     

Impressive Pseudotumoral Proliferative Nodules in a Giant Congenital Nevus of a Newborn

Abstract: The potential for malignant transformation of a giant congenital melanocytic nevus (GCMN), although rare, should be considered, especially in proliferative lesions that have nodules on their surface, as they can clinically and histologically mimic melanoma and generally have a poor prognosis. We present the case of a newborn boy with a giant nevus of uneven blackish color on the back with variable degrees of intensity of pigmentation, almost entirely covered by nodules of large and variable sizes, soft texture, and a tendency to ulcerate and bleed. The unusual clinical and histologic appearance made the case particularly interesting and featured a not well‐defined biologic behavior, thus deserving a radical surgical approach to fulfill diagnostic and therapeutic aims.