Polystyrene nanoplastics affect the human ubiquitin structure and ubiquitination in cells: a high-resolution study.

Humans are estimated to consume several grams per week of nanoplastics (NPs) through exposure to a variety of contamination sources. Nonetheless, the effects of these polymeric particles on living systems are still mostly unknown. Here, by means of CD, NMR and TEM analyses, we describe at an atomic resolution the interaction of ubiquitin with polystyrene NPs (PS-NPs), showing how a hard protein corona is formed. Moreover, we report that in human HeLa cells exposure to PS-NPs leads to a sensible reduction of ubiquitination. Our study overall indicates that PS-NPs cause significant structural effects on ubiquitin, thereby influencing one of the key metabolic processes at the base of cell viability.

The potential diagnostic and predictive role of anaplastic lymphoma kinase (ALK) gene alterations in melanocytic tumors.

OBJECTIVE: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role. MATERIALS AND METHODS: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid". RESULTS: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein. CONCLUSIONS: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

Tuning of polyurethane foam mechanical and thermal properties using ball-milled cellulose.

Cystalline-Cc and ultra-milled Amorphous-Ca cellulose were used as reactive filler to tune the performances of composite polyurethane-cellulose-foams, PUC. The effect of Cc and Ca on chemo-physical and mechanical properties of PUC was analysed through FTIR, morphological analysis, thermal conductivity and compression measurements. FTIR results show that, both Cc and Ca react with isocyanate through the OH functional groups contributing to the formation of a tough cellulose-polyurethane network. Morphological observations show that the addition of both Cc and Ca induces a decrease of average cell-size compared to the pristine-PU, thus confirming that they act as nucleating agent. In addition, the better dispersion of the Ca in the polyol, with respect to Cc induces, a finer cell leading to a reduction of the thermal conductivity around 33 % (for the composite loaded with 20 %wt-Ca) with respect to pristine-PU. Finally, the addition of Ca highly reactive modifies the mechanical behaviour from rigid-brittle to semi-rigid.

Effect of cellulose structure and morphology on the properties of poly(butylene succinate-co-butylene adipate) biocomposites.

Composites based on poly(butylene succinate-co-butylene adipate) (PBSA) containing amorphized and crystalline cellulose reinforcements have been prepared and characterized. In order to improve the polymer/filler interfacial adhesion, an efficient compatibilizing agent has been synthesized by chemical modification of PBSA and characterized by FT-IR, FT-NIR and (1)H NMR spectroscopy. Uncompatibilized and compatibilized composites have been tested through morphological, mechanical, calorimetric and thermogravimetric analysis. Moreover, water vapor permeability and biodegradation kinetics of composites have been investigated. The addition to PBSA of cellulose fillers differing from each other by crystallinity degree and morphology, and the use of a compatibilizing agent have allowed modulating tensile and thermal properties, water vapor transmission rate and biodegradation kinetic of the composites.

Amorphized cellulose as filler in biocomposites based on poly(ɛ-caprolactone).

Amorphous cellulose particles, obtained through a solvent-free mechano-chemical process, have been tested for the first time as a potential filler for biodegradable composites based on poly(ɛ-caprolactone) (PCL). Commercial cellulose fibers have been also tested for comparison. An effective interfacial strategy based on a compatibilizing agent, a modified PCL, has been used to improve the polymer/filler interfacial adhesion. Composites have been tested through physico-mechanical characterizations and soil burial degradation tests, in order to evaluate the influence of cellulose structure and morphology and polymer/filler interfacial adhesion on the final properties of the realized materials. The use of the amorphous cellulose particles combined with the presence of a suitable interfacial agent has allowed to modulate relevant technological properties of the realized composites, such as tensile and thermal properties, water absorption, water vapor transmission rate and biodegradation kinetic.

Role of ß-catenin expression in paediatric mesenchymal lesions: a tissue microarray-based immunohistochemical study.

Beta-catenin is a major protein in the Wnt signalling pathway. Although it has been studied in various types of carcinoma, little is known about its expression in mesenchymal tumours. In this study 41 specimens of a variety of mesenchymal childhood tumours were compared to 24 samples of the corresponding adult tumours to assess the diagnostic value of nuclear ß-catenin expression using tissue microarray-based immunohistochemistry. Similar to adult sarcoma and fibromatosis, ß-catenin was not expressed in the majority of childhood sarcomas, and its nuclear translocation was detected in paediatric fibromatosis; non-negligible levels of nuclear staining in other tumour types demonstrate Wnt pathway activation in mesenchymal neoplasms of childhood and adolescence.

A multitechnique approach to assess the effect of ball milling on cellulose.

This paper presents a detailed analysis of effect induced by a dry ball milling process on cellulose structure, morphology and properties. The partial amorphization of cellulose was qualitatively estimated by ATR-FTIR analysis. Through WAXD analysis the crystallinity index and the mean size of the cellulose crystallite domains were calculated, both these parameters showing a progressive decrease as a function of the milling time. In particular, crystallinity index decreased from 0.53 to 0.15 after 60min ball milling, whereas the mean size of the cellulose crystallite domains showed a reduction from the original value of about 4.0nm up to about 3.4nm after 30min. These quantitative results were confirmed by 13C CP-MAS NMR analysis and measurements of the proton spin-lattice relaxation time in the rotating frame (T1ρ1H). Moreover, the increasing of the amount of water absorbed by cellulose samples (from 7.3wt% for untreated cellulose up to 11.6wt% for the cellulose sample ball milled for 60min) and the reduction of the thermal stability were evaluated by TGA. Finally, SEM analysis revealed that the original fibrous structure almost disappeared and was modified to a quasi-circular shape.

Leiomyosarcoma of the submandibular gland. Report of a case and review of the literature.

This report describes the first case of primary leiomyosarcoma of the submandibular salivary glands and emphasizes the role of immunohistochemical study for a correct diagnosis of this tumour. In line with results of international literature, we associated surgery with radiotherapy and 2 years postoperatively there was no sign of recurrence.

Loss of oestrogen receptor beta, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours.

AIMS: Ovarian granulosa cell tumour (OGCT) is a sex-cord stromal tumour with a general trend toward late relapse and/or metastasis. However, mortality rate corrected for long-term follow-up shows that about 50% of patients die within 20 years of diagnosis. Classical clinicopathological parameters are unable to predict the biological behaviour of OGCT. The involvement of a recently characterized subtype of oestrogen receptor, ERbeta, in ovarian carcinogenesis has been hypothesized. METHODS AND RESULTS: We examined by immunohistochemistry the expression of ERbeta, proliferating cell nuclear antigen (PCNA) and p53 in a selected series of 30 OGCT, to evaluate their role in the prognostic evaluation of this tumour. Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections. Results were compared with the DNA-ploidy of the tumours (evaluated by image analysis) and with the follow-up data of the patients. CONCLUSIONS: Loss of ERbeta expression, high PCNA expression and aneuploidy, characterized a subgroup of OGCT with a worse outcome. The identification of a high-risk subclass of OGCT may be of primary importance in addressing appropriate therapeutic strategies, offering the chance to prevent relapses and metastases by using adjunctive, specifically targetted, more aggressive therapies.

Novel graft PLLA-based copolymers: potential of their application to particle technology.

This study describes the synthesis of novel biodegradable graft copolymers based on a backbone of poly (L-lactic acid) (PLLA) on which short blocks of polyacrylamide (PAcr) were grafted. Preliminary results of their potential in the field of controlled-release technologies also have been reported. The copolymers have been synthesized through the radical polymerization of acrylamide initiated by a peroxide in the presence of PLLA. Two different methodologies of synthesis, namely, in solution and in emulsion, have been tested. The structure of the copolymers was studied by (1)H-NMR and infrared spectroscopy and by differential scanning calorimetry (DSC) and cytotoxicity tests were conducted to assess their biocompatibility. The copolymers were used to prepare particles by the emulsion-solvent evaporation technique. The shapes and dimensions of the particles were dependent on the polymer type and concentration used. The surfaces of the particles were modified by the presence of polyacrylamide residues, as demonstrated by zeta-potential measurements. The release behavior of the particles was assessed by encapsulating rhodamine B as the model compound. The release was faster for the particles prepared by the grafted polymer as a consequence of its increased hydrophilicity. Based on these novel biomaterials, preliminary results suggest a potential of the particles for peroral or parenteral drug delivery.

DNA ploidy and cyclin D1 expression in basal cell carcinoma of the head and neck.

Basal cell carcinomas (BCCs) may be subdivided into primary with a favorable biologic course (BCC1) and recurrent and/or metastatic (BCC2). No clear association between primary tumor location, histologic subtype, or other clinicopathologic variables and predisposition for BCC2 has been found. Histopathologic criteria are limited for prognostication. To identify prognostic factors useful for planning therapy, we studied cyclin D1 immunohistochemical expression, DNA ploidy, and epiluminescence light microscopic (ELM) patterns in 60 cases of BCC (30 BCC1 and 30 BCC2) in the head and neck region, half of which were hyperpigmented. Cyclin D1 was absent in 27 cases, expressed at low level in 4 cases, and overexpressed in 30 cases. Seven BCCs were euploid, 28 exhibited a mixed cellular population, and 25 were aneuploid. Among aneuploid tumors, hypodiploidy was found in 12. Among the 30 pigmented carcinomas, only 15 showed a typical ELM pattern. No association between pigmentation and more aggressive biologic behavior of BCC was found. These results and follow-up data seem to indicate that an unfavorable outcome can be predicted by hyperexpression of cyclin D1, aneuploidy, and an atypical ELM pattern for pigmented cases. A definite hypodiploid peak was associated with worse prognosis. The analysis of cyclin D1 expression and DNA ploidy may help identify BCC with an aggressive phenotype and a poor clinical outcome.

Interaction between bcl-2 and P53 in neoplastic progression of basal cell carcinoma of the head and neck.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent tumor of the human skin and generally shows a favourable clinical behaviour. However, a percentage of BCC grows aggressively, infiltrating contiguous structures, sometimes giving distant metastases. MATERIALS AND METHODS: Bcl-2 and p53 protein expression was studied immunohistochemically in 60 cases of BCC (30 non-aggressive, BCC1 and 30 aggressive cases, BCC2) of the head and neck region with a complete clinical follow-up. RESULTS: All the BCC1 showed distinct cytoplasmic staining for bcl-2. The intensity of staining ranged from intermediate to high, with only three cases showing low positivity. Among BCC2, none of the 30 cases showed positivity for bcl-2. Bcl-2 expression was directly correlated with the BCC1 sub-type and a favourable clinical follow-up (p<0.01). Among BCC1, 27 cases were found negative for p53 protein expression while 3 exhibited only a low immunoreactivity. Among BCC2, 11 out of 30 cases showed an intermediate immunoreactivity, and 18 out of 30 exhibited high positivity for p53 protein. The expression of p53 protein correlated inversely with cellular differentiation (p<0.01). CONCLUSION: From the analysis of these results it is reasonable to consider bcl-2 and p53 protein expression as useful discriminating prognostic factors in the evaluation of BCCs of the head and neck region. In fact, the finding of clones expressing bcl-2 in a case of BCC may be indicative of an "indolent" cellular neoplastic phenotype. In other words, bcl-2 could be used as a "clonal marker" of a still favourable clinical behaviour. Conversely, the partial or complete loss of bcl-2-bearing neoplastic clones during histological transformation, with the appearance of clones expressing p53 protein in a BCC could be considered a hallmark of transition from a low-to high-grade malignancy, characterized by the emergence of cellular clones with a more aggressive phenotype, responsible for worse clinical behaviour.

Epithelioid sarcoma: report of two cases diagnosed by fine-needle aspiration biopsy with immunocytochemical correlation.

Epithelioid sarcoma (ES) is an aggressive soft-tissue malignant tumor generally arising in the distal extremities of young adults. The microscopic diagnosis of ES is often difficult because of its rarity and its possible confusion with other malignant tumors or even with benign granulomatous processes. Two cases of ES and a recurrence of one of these tumors, diagnosed by fine-needle aspiration biopsy (FNAB), are reported. Cytologic smears were quite similar in both cases including the relapse, showing single or loosely arranged groups of medium to large atypical cells. Single cells had well-defined eosinophilic cytoplasms and one or more atypical, eccentrically located nuclei, resulting in a plasmacytoid appearance. Nuclei had fine granular chromatin and one or two large nucleoli. The cells sometimes palisaded along the edges of necrotic material. The immunocytochemical stains showed diffuse cytoplasmic positivity for cytokeratins (CAM 5.2) and both cytoplasmic and cell membrane positivity for vimentin, while S-100 protein and HMB 45 immunostaining were negative, thus supporting the cytological diagnosis of ES, which was subsequently proven on the surgical samples. Diagn. Cytopathol. 1999;21:405-408.

Neuroendocrine (Merkel cell) carcinoma of the oral mucosa: report of a case with immunohistochemical study and review of the literature.

Merkel cell carcinoma (Mcc) is an uncommon and aggressive tumour with neuroendocrine features that occur predominantly in the head and neck region. The rarity of this tumour, especially when it arises in the oral mucosa, makes both early identification and standardisation of treatment difficult, particularly as regards complementary treatment. The availability of monoclonal antibodies with restricted specificity for some antigens thought to be related to neuroendocrine carcinomas, such as Merkel cell carcinoma, and ultrastructural studies offer some new leads to investigation. This has allowed, a greater number of these tumours to be discovered, thereby increasing the chances of effective management. A case of Mcc of the floor of the mouth is reported, together with the results of cytokeratin, neuron specific enolase and chromogranin immunohistochemistry.

Epithelioid hemangioendothelioma of the larynx.

Epithelioid hemangioendothelioma is an uncommon vascular tumor of the soft tissues. Several reports have described this tumor in visceral locations such as liver, lung, and brain. To the best of our knowledge this is the first report of an immunohistochemical and ultrastructural study of a primary epithelioid hemangioendothelioma occurring in the larynx. Difficulties concerning the differential diagnosis and clinical problems arising from surgical therapy in the laryngeal area are also discussed.

Morphometric analysis of AgNORs in uveal malignant melanoma.

OBJECTIVE: To define the value of silver-stained nucleolar organizer regions (AgNOR) in the evaluation of uveal malignant melanomas (MM). STUDY DESIGN: Morphometric analysis of AgNORs was performed on 30 uveal MM of spindle A, B, epithelioid and mixed cell types. Findings were compared with cytotype, largest tumor dimension (LTD) and clinical outcome. RESULTS: AgNOR mean perimeter (MP) was 3.76 microns (SD 1.21, range 1.79-8.51 microns) in A, 5.05 microns (SD 1.96, range 1.79-16.41 microns) in B and 6.15 microns (SD 3.86, range 1.79-33.80 microns) in epithelioid MM; mean area (MA) was 0.86 micron 2 (SD 0.60, range 0.20-2.78 microns 2) in A, 1.58 microns 2 (SD 1.11, range 0.20-9.63 microns 2) in B and 2.34 microns 2 (SD 2.10, range 0.20-15.27 microns 2) in epithelioid MM; the aspect ratio (AR) was 3.10 (SD 0.19, range 2.90-3.35) in A, 5.80 (SD 2.07, range 3.77-9.32) in B and 12.22 (SD 2.84, range 8.11-15.81) in epithelioid MM. From comparing MA and RA with follow-up, it seemed that MM with a good prognosis (spindle A and a subgroup of B tumors, B1) exhibited the lowest MA and AR values, while MM with poorer clinical behavior (epithelioid and a second subgroup of spindle B MM, B2) showed the highest. No correlation was found between AgNORs and LTD. CONCLUSION: AgNORs may contribute to the prognostic evaluation of uveal MM.

[Etio-pathogenic considerations on the development of multiple bone cysts in the mandible. Report of a clinical case]. / Considerazioni etiopatogenetiche sullo sviluppo delle cisti ossee essenziali della mandibola. Presentazione di un caso clinico.

A case of a mandibular cyst, missing of wall lining and containing some solid material is described. The histologic examination showed that this material consisted of osteofibrous tissue with regressive phenomena, inflammatory cells and hyperplastic nervous tissue. On the basis of clinical and histologic findings it is suggested to be a solitary cyst and the solid material due to a local response to an injury suffered by the patient who is a sport practitioner.

Fine needle aspiration (FNA) biopsy of orbital masses: a critical review of 51 cases.

FNA biopsy of 51 orbital masses is critically reviewed. Aspiration was performed with a 23 G needle inserted by an ophthalmologist; the smears were prepared by a cytologist. Forty-two cases (83%) were correctly diagnosed as benign or malignant either with (68%) or without (15%) correct specification of the histology. There were two false-negative and seven inadequate cases. Immunocytochemical stains were performed in five cases using the following antibodies: L26 (Pan B), UCHL1 (Pan T), kappa and lambda immunoglobulin light chains (three cases) in order to distinguish inflammatory pseudotumours from low-grade non-Hodgkin's lymphomas. In two cases we used CAM 5.2 (a monoclonal cytokeratin cocktail) and vimentin to ascertain the epithelial origin of two metastatic tumours. In five other cases cytospins were not adequately cellular for immunocytochemistry. Insufficient material and one false-negative sample were obtained from very fibrotic lesions or from posteriorly located lesions. The results are discussed and compared with other series reported in the literature. Orbital FNA biopsy may be considered a useful tool in the diagnostic approach to orbital masses in which the relatively high number of inadequate aspirations is offset by a low cost-benefit ratio.