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Alessandro Franchi

Publications and source records attributed to Alessandro Franchi.

At least 19 recordsLinked to original sources
PubMed2007

Primary cutaneous osteosarcoma of the scalp: a case report and review of the literature.

We report on an 84-year-old man with a solitary, nodular lesion on the scalp. The patient had been previously submitted to electrodessications of the scalp due to multiple solar keratoses. Histopathologically, the lesion showed features of a high-grade conventional osteoblastic osteosarcoma involving the dermis. Computed tomography showed no involvement of the underlying bone tissues. Clinical examination and extensive total body radiologic workup revealed absence of bone lesions in any body site, thus suggesting a final diagnosis of primary cutaneous extraskeletal osteosarcoma. The clinico-pathological features of the case are discussed in light of the rare cases previously described in the literature.

Aged, 80 and over↗
PubMed2006

Expression of p16 in sinonasal malignant melanoma.

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.

Aged↗
PubMed2006

Microsatellite instability as an indicator of malignant progression in laryngeal premalignancy.

BACKGROUND: Microsatellite instability (MSI) is considered a novel marker of genetic instability, and preliminary studies have shown that it may provide useful information in assessing the risk of malignant progression in preinvasive lesions. METHODS: We analyzed MSI in serial biopsy specimens from 10 patients with preinvasive laryngeal lesions and corresponding metachronous laryngeal cancers compared with biopsy specimens of similar lesions without malignant transformation from 20 subjects in a match-paired analysis. MSI was determined by assessing the status of 14 microsatellite markers (chromosome loci: 2p16, 3q21-24, 4q12, 9p21, 13q14, 16q22.1, 17p12 and 21q21) in DNA biopsy specimens. RESULTS: MSI(+) (aberration at two or more loci) was detected in seven of 10 patients with premalignant lesions progressed to carcinoma, whereas only four of the 20 biopsy specimens from control subjects showed an unstable phenotype (p < .01). Interestingly, preinvasive laryngeal lesions with MSI at hMSH2/hMSH6 loci frequently had instability at one or more additional loci and were considered as MSI(+) (overall in eight of 12 cases: six premalignant lesions progressed to cancer and one without progression of the original laryngeal lesion, p < .01). The immunohistochemical analysis of the hMSH2 protein expression in our series, however, did not suggest its involvement in laryngeal carcinogenesis. CONCLUSIONS: Our study indicates that MSI is more common in preneoplastic laryngeal lesions progressing to cancer, thus suggesting that microsatellite status assessment may be useful in determining the risk of malignant progression in patients with preinvasive laryngeal lesions for whom chemopreventive and multiple endoscopic protocols can be attempted.

Adult↗
PubMed2006

Inducible nitric oxide synthase activity correlates with lymphangiogenesis and vascular endothelial growth factor-C expression in head and neck squamous cell carcinoma.

Nitric oxide (NO) is a diatomic free radical molecule that has been implicated in tumour angiogenesis and progression of head and neck squamous cell carcinoma (HNSCC). However, the mechanism underlying the effect of NO on tumour spread remains largely unknown. Tumour lymphangiogenesis has recently received considerable attention and there is increasing evidence that it is relevant for metastasis to lymph nodes in HNSCC. Here, we study the correlation between inducible NOS synthase (iNOS) activity and lymphangiogenesis in a series of 60 HNSCCs and the possible involvement of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. HNSCC presenting with lymph node metastasis had a significantly higher lymphatic vessel density in both the tumour mass and the peritumour area (p = 0.006 and p = 0.001, respectively). Similarly, tumours with lymph node metastasis showed greater lymphatic vessel area than tumours with no lymph node involvement (p = 0.001 for intratumour lymphatics and p < 0.001 for peritumour lymphatics). iNOS activity measured in specimens from the tumour periphery correlated strongly with both lymphatic vessel density and lymphatic vessel area (p = 0.01, rs = 0.45 and p < 0.001, rs = 0.725, respectively). Conversely, these correlations were not observed in specimens from the tumour core. In addition, VEGF-C mRNA expression was significantly elevated in tumours with high iNOS activity (p = 0.008, rs = 0.563), and VEGF-C expression correlated positively with the presence of lymph node metastases (p = 0.03). In vitro, in the A431 human squamous carcinoma cell line, exogenous and endogenous stimulation of the iNOS pathway led to up-regulation of VEGF-C, which was blocked by the NOS inhibitor L-NNA. Taken together, our results indicate that iNOS activity may promote lymphangiogenesis and spread to lymph nodes in HNSCC, with the possible involvement of VEGF-C.

Aged↗
PubMed2006

Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma.

The Notch signaling has been implicated in the regulation of self-renewal of adult stem cells and differentiation of precursors along a specific cell lineage, in normal embryonic development and organogenesis. There is also evidence that signaling through Notch receptors regulate cell proliferation and cell survival in several types of cancer, with opposing results depending on tissue context. No data are available in the literature concerning modulation of the expression of Notch receptors, and their ligands, in human cutaneous malignant melanoma. Here, we have investigated, for the first time, the expression of Notch-1, Notch-2, Jagged-1, Jagged-2 and Delta-like 1 proteins, by immunohistochemistry, in a series of benign and malignant human melanocytic lesions: five common melanocytic nevi, five 'dysplastic nevi' and 20 melanomas (five in situ, five T1-T2, five T3-T4 and five metastatic melanomas). We found that the expression of Notch-1 and Notch-2, as well as Notch ligands, was upregulated in 'dysplastic nevi' and melanomas as compared with common melanocytic nevi. These results indicate that the activation of Notch may represent an early event in melanocytic tumor growth and upregulation of Notch signaling may sustain tumor progression.

Adult↗
PubMed2006

Enterogenous cyst of the testis.

Enterogenous cyst is a rare congenital lesion generally located in the mediastinum or the abdominal cavity. We reported the first case of testicular enterogenous cyst in a 55-year-old white male presented with testicular pain and a gradually enlarging left scrotal mass with a 2-week duration.

Cysts↗
PubMed2006

Well-differentiated chondrosarcoma of the humerus with prominent granular cell component: a hitherto unreported occurrence.

We report the case of a well-differentiated chondrosarcoma of the proximal humerus in a 60-year-old man that featured a prominent component of granular cells, the granules being shown by electron microscopy to be lysosomal. Although secondary granular cell changes have been described in a large variety of tumor types, this is, to the best of our knowledge, the first documentation of this phenomenon in a skeletal chondrosarcoma.

Bone Neoplasms↗
PubMed2005

Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma.

Protease-activated receptors (PARs) are members of the G protein-coupled receptor superfamily that are activated by the proteolytic cleavage of their amino terminal domain. PAR-1 activation by thrombin results in several biologic effects, including platelet adhesion to other cells or extracellular matrix, fibroblast, and endothelial cell growth, whereas PAR-2, activated by trypsin, has mainly a proinflammmatory and angiogenetic role. PAR-1 and PAR-2 modulate cell proliferation in physiopathologic cell invasion processes, suggesting that they may play a role in the setting of cancer growth and metastasis. Here, we have investigated the expression of PAR-1 and PAR-2 proteins by immunohistochemistry in a series of benign and malignant melanocytic lesions: 20 melanocytic lesions (10 common melanocytic nevi and 10 atypical or "dysplastic" melanocytic nevi) and 50 melanomas (10 in situ melanomas, 10 melanomas T1, 10 melanomas T2, 10 melanomas T3 to T4, and 10 metastatic melanomas). PAR-1 was significantly overexpressed in atypical nevi and melanomas in comparison with common melanocytic nevi. PAR-2 was strongly and diffusely expressed by immunohistochemistry in all melanocytic lesions, with no statistically significant differences between nevi and melanomas. Because we found a differential expression in PAR-1 protein, but not in PAR-2, we next investigated the expression of PAR-1 messenger RNA (mRNA) by ribonuclease protection assay in paraffin-embedded tissues using a paraffin block RNA isolation procedure. Similarly to immunohistochemical results, PAR-1 mRNA expression was significantly higher in atypical nevi and melanomas in comparison with common nevi and controls. Overexpression of PAR-1 in atypical nevi and melanomas supports a role for PAR-1 in the initial phases of melanoma development as well as in tumor progression and metastasis. Conversely, the significance of PAR-2 up-regulation in both benign and malignant melanocytic lesions requires further research.

Adult↗
PubMed2004

Azidothymidine induces apoptosis and inhibits cell growth and telomerase activity of human parathyroid cancer cells in culture.

UNLABELLED: Telomerase activity has been correlated to parathyroid carcinoma. Because its role in acquisition of a malignant phenotype by parathyroid cells is unclear, we treated telomerase-positive cultured human parathyroid cancer cells with the telomerase inhibitor AZT, evaluating cell telomerase activity, cytotoxic effects, growth, and morphological changes. In vitro exposure of these cells to AZT correlated with inhibition of cell proliferation. INTRODUCTION: Parathyroid carcinoma represents an uncommon cause of primary hyperparathyroidism, whose spectrum of clinical presentation, degree of malignancy, and prognosis are difficult to be properly identified. Neck surgery, specifically an en bloc resection of primary tumor, is the only curative treatment. Alternatively, affected patients could undergo repetitive palliative surgical exeresis of metastatic nodules. It has been previously shown that telomerase activity is specifically present in parathyroid carcinoma cells, being absent in hyperplastic and adenomatous tissues. Thus, determination of telomerase activity could represent either a useful diagnostic molecular marker for human parathyroid carcinoma or a potential target for pharmacological intervention in a malignant neoplasia usually resistant to chemo- and radiotherapeutic interventions. MATERIALS AND METHODS: To further investigate the role of telomerase activity in acquisition of a malignant phenotype by parathyroid cells, we treated telomeric repeat amplification protocol-positive cultured human parathyroid cells with the telomerase inhibitor zidovudine, 3'-azido-3'deoxythymidine (AZT), evaluating cell telomerase activity, growth characteristics, potential cytotoxic effects, and morphological changes. RESULTS: Our findings indicate that in vitro exposure of human parathyroid cancer cells to AZT resulted in intracellular accumulation of AZT-monophosphate (AZT-MP) and inhibition of telomerase, which correlate with inhibition of human parathyroid cancer cell proliferation. Moreover, we also found that AZT induced an apoptotic rather than a necrotic type of cellular death. None of these effects were observed in human adenomatous parathyroid cells in culture. CONCLUSIONS: Altogether these results indicate that AZT may be a highly effective agent against cancer parathyroid cells proliferation, which is an extremely important observation for a neoplasia which shows lack of response to classical pharmacological and physical antiblastic treatments.

Aged↗
PubMed2004

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells.

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses syndrome, which is characterized by the formation of osteochondromas and an increased risk of chondrosarcomas and osteosarcomas. However, despite its putative tumor-suppressor function, little is known of the contribution of EXT1 to human sporadic malignancies. Here, we report that EXT1 function is abrogated in human cancer cells by transcriptional silencing associated with CpG island promoter hypermethylation. We also show that, at the biochemical and cellular levels, the epigenetic inactivation of EXT1, a glycosyltransferase, leads to the loss of heparan sulfate (HS) synthesis. Reduced HS production can be reversed by the use of a DNA demethylating agent. Furthermore, the re-introduction of EXT1 into cancer cell lines displaying methylation-dependent silencing of EXT1 induces tumor-suppressor-like features, e.g. reduced colony formation density and tumor growth in nude mouse xenograft models. Screening a large collection of human cancer cell lines (n=79) and primary tumors (n=454) from different cell types, we found that EXT1 CpG island hypermethylation was common in leukemia, especially acute promyelocytic leukemia and acute lymphoblastic leukemia, and non-melanoma skin cancer. These findings highlight the importance of EXT1 epigenetic inactivation, leading to an abrogation of HS biosynthesis, in the processes of tumor onset and progression.

Animals↗
PubMed2004

Tumor lymphangiogenesis in head and neck squamous cell carcinoma: a morphometric study with clinical correlations.

BACKGROUND: Tumor metastasis to regional lymph nodes via the lymphatic system represents the first step of dissemination in head and neck squamous cell carcinoma (HNSCC) and serves as a major prognostic indicator for disease progression and as a guide for therapeutic strategies. In the current study, the authors investigated whether tumor lymphangiogenesis may be related to the risk of lymph node metastasis and to clinical outcome in patients with HNSCC. METHODS: Immunostaining for the lymphatic marker D2-40 was used, and lymphangiogenesis was quantified within the tumor and in the peritumoral area in 52 HNSCC specimens using computer-assisted morphometric analysis. RESULTS: Lymphatic vessels were found to be significantly more numerous and larger in the peritumoral area compared with within the tumor, and the number and relative area of intratumoral and peritumoral lymphatics was significantly higher in HNSCC cases with lymph node metastasis. Multivariate analysis demonstrated that high peritumoral lymphangiogenesis (above the median value) was associated with an increased risk of developing lymph node metastasis. No correlation was found between tumor lymphangiogenesis and the disease-free or overall survival in the current series. CONCLUSIONS: The results indicate that peritumoral lymphangiogenesis may be an indicator of the risk of lymph node metastasis in patients with HNSCC.

Aged↗
PubMed2004

Persistent contrast enhancement by sterically stabilized paramagnetic liposomes in murine melanoma.

In the present research, we investigated the use of paramagnetic liposomes as contrast agents (CAs) for the detection of solid tumors. The liposomes were sterically stabilized by a polyethylene glycol (PEG) coating, and their size was constrained to approximately 100 nm. Dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylene-triaminepentaacetate (DMPE-DTPA) was used as the gadolinium-carrying fatty acid chain. The relaxation properties were characterized through nuclear magnetic relaxation dispersion (NMRD) measurements, and analyzed with the use of theories and computer programs that are adequate for slowly rotating systems. Their relaxivity at 1.5 T was found to be acceptable for in vivo use. We then tested the liposomes against B16-F10 murine melanomas using standard T1-weighted schemes at 1.5 T, and concentrations corresponding to 0.03 mmol/kg of gadolinium (i.e., three to six times lower than the concentration of the small gadolinium complexes in clinical use). The blood half-life was found to be 120 +/- 20 min. The experiments show a good contrast enhancement in the tumor (33% +/- 22%) 2 hr after administration, a further increase (43 +/- 27%) 20 hr after administration, and a decrease (25% +/- 14%) 54 hr after administration. High persistence of the CA was also observed in the liver and intestine, as expected in a hepatobiliar excretion pathway.

Animals↗
PubMed2004

Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma.

The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma.

Adult↗
PubMed2004

Central low-grade osteosarcoma with pagetoid bone formation: a potential diagnostic pitfall.

Central low-grade osteosarcoma is an uncommon form of osteosarcoma, which is often difficult to distinguish from benign bone lesions. We reviewed the radiographic studies, the histologic material and the clinical records of two patients with central low-grade osteosarcoma that closely simulated the histologic appearance of Paget's disease of bone. The patients were two women aged 46 and 53 years. Radiologically, they presented a large ill-defined densely sclerotic lesion involving the proximal tibia. Both lesions only focally presented the conventional histologic appearance of central low-grade osteosarcoma, with a proliferation of fibroblast-like cells embedded in a dense collagenous stroma and irregular anastomosing tumor bone trabeculae. The most striking feature was the presence of extremely thickened irregular plates of bone with an irregular mosaic pattern of cement lines that closely resembled that of Paget's disease of bone. One patient, who had been initially treated for Paget's disease for 7 years, experienced disease progression. At resection of proximal tibia, there was evidence of dedifferentiation to high-grade osteosarcoma. After 2 months, she developed local recurrence that was treated with above-knee amputation, followed by chemotherapy. She died with multiple lung metastases 4 months later. The other patient is alive 9 months after wide tumor resection. These cases further expand the spectrum of central low-grade osteosarcoma, and underscore the diagnostic difficulties in separating central low-grade osteosarcoma from benign bone diseases, which may lead to delay in diagnosis, inadequate treatment, and eventually to dedifferentiation. Recognition of this variant of central low-grade osteosarcoma is based on the aggressive radiologic appearance and on adequate tumor sampling for histologic examination.

Bone Neoplasms↗
PubMed2004

Epidermal growth factor receptor and p53 expression in T1-T2 glottic cancer involving the anterior or posterior commissure.

OBJECTIVE: We surveyed retrospectively the expression of epidermal growth factor receptor (EGFR) and p53 in cases of T1-T2 glottis cancer involving the anterior (AC) or posterior commissure (PC) subsites to check for differences possibly explaining the different prognoses of cancer at these subsites. MATERIAL AND METHODS: Between 1970 and 1995, 15 patients with T1-T2 primary glottis cancer involving the PC, either partly or entirely, were treated. Thirty more cases were selected among 184 patients treated during the same time period for AC glottis cancer, to match the former cases with regard to age, sex, tumor stage, smoking habits and alcohol consumption. RESULTS: A significantly higher frequency of EGFR expression occurred in PC than in AC cancer. CONCLUSION: These results, and the anatomy of the PC subsite, may explain the more frequent recurrence of T1-T2 PC compared to T1-T2 AC cancer and why radiotherapy achieves worse results in T1-T2 PC cancer than in AC cancer of comparable T grade.

Aged↗
PubMed2004

Atypical CD30+ cutaneous lymphoid proliferation in a patient with tuberculosis infection.

We describe the case of a 65-year-old woman affected by a diffuse lymphadenopathy consistent with tuberculous infection who developed a papular eruption on the head and neck region. Histopathologic examination of one papule showed an atypical CD30+ lymphoid infiltrate, which initially was cause of concern for the pathologists but was eventually regarded as reactive in nature. The case reported herein enlarges the spectrum of inflammatory infiltrates in which atypical CD30+ cells may be found. Since the reactive atypical CD30+ cells are morphologically similar to those cells observed in CD30+ lymphoproliferative disorders, including lymphomatoid papulosis, complete clinical history and laboratory findings are necessary to make the final and correct diagnosis. Although the pathogenetic relevance of the presence of CD30+ cells within the cutaneous infiltrate of patients with systemic tuberculosis remains to be determined, our findings support the hypothesis that the cytokine profile associated with tuberculosis may not be strictly TH1-like, and that a TH1-like to TH2-like switch may also occur.

Aged↗
PubMed2003

Effects of natural organic matter and solution chemistry on the deposition and reentrainment of colloids in porous media.

The role of humic acid in the transport of negatively charged colloids through porous media was examined. Adsorption of humic acid on latex colloids and silica collectors reduced the deposition of suspended particles and enhanced the reentrainment of deposited particles in porous media. These effects are considered to arise from additional electrostatic and steric contributions to the repulsive interaction energy due to the adsorption of negatively charged humic acid on both the suspended particles and the media collectors. At low ionic strength reversible deposition in shallow secondary minima is hypothesized to be the principal attachment mechanism, independent of the presence of humic acid. It is proposed that under these solution conditions, particle deposition and reentrainment are the result of a dynamic process, in which particles are continuously captured and released from secondary minima. At higher ionic strengths, deposition may be regarded as a combination of two mechanisms: capture in the primary well and capture in the secondary minimum. Theoretical calculations of the attachment efficiency were conducted using two existing mathematical models. The first model is based on deposition in the primary well (interaction force boundary layer, IFBL), and the second model is based on the Maxwell kinetic theory and deposition in the secondary minimum (Maxwell model). Simulations conducted with the Maxwell model provide significantly better fits of the experimental results than those conducted with the IFBL model.

Colloids↗