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Biomedical subjects

C Clemente

Publications and source records attributed to C Clemente.

At least 55 records · Page 3Linked to original sources

Biological activity and clinical efficacy of intravenous high-dose thymopentin in metastatic melanoma patients.

Eight patients with cutaneous metastatic melanoma were submitted to high-dose intravenous thymopentin (TP5) treatment for 5 weeks: three patients received 1 g three times a week, three received 1 g daily and two received 2 g daily. Four out of eight patients presented a partial response of cutaneous lesions lasting for 1-7 months, and six remain alive with evidence of disease after a follow-up of 2-7 months. A remarkable histologic observation is the presence of tumour necrosis, which was seen as both single cells and large confluent areas. The majority of lymphoid cells present in the tumour are CD45RO+ and CD4+. The CD4+ cells might play an important role in the anti-tumour immune local response by secreting cytokines and inducing apoptotic and necrotic cell death. This hypothesis seems to be confirmed by the presence of a high number of CD4+ cells around intratumoral vessels, while the presence of endovascular micro-thrombosis provides indirect evidence of cytokine activity. Cellular lysis may be produced by the activity of both CD8+ and CD4+ lymphoid cells. The role of TP5 may be an activation of CD4+ and CD8+ lymphoid cells. Clinical and pathological data indicate that TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases.

Adjuvants, Immunologic↗

Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2-matched primary human melanomas.

We have shown previously that peripheral blood lymphocytes (PBL) of patients with metastatic melanoma include cytotoxic T-cell clones that recognize Melan-A/MART-1 in a HLA-A2-restricted fashion. Such clones preferentially use the variable (V) regions TCRBV14 or TCRBV7 in the beta-chain of their T-cell receptor (TCRB). It was not known, however, whether this finding is associated with the presence of the HLA-A2 allele in tumor tissue and whether evidence of the predominance of these TCRBV families can also be observed in primary tumor tissue. To address these issues, we have used a semiquantitative PCR to examine the TCRBV repertoire in six HLA-A2-matched primary melanomas in comparison with their autologous PBL. Although each patient had his or her own pattern of skewed TCRBV utilization, in all patients, T-cells that used TCRBV14 were significantly overrepresented in the neoplastic site compared with PBL. All of the primary tumors studied had detectable expression of Melan-A/MART-1 and gp100, and immunohistochemical analysis confirmed the presence of the HLA-A2 allele. Additional samples of Melan-A/MART-1-positive, gp100-positive primary melanomas from six non-HLA-A2 patients and four autologous normal skin controls failed to reveal a TCRBV14 predominance in such tissues. These results point to a role of TCRBV14 T lymphocytes in the HLA-A2-restricted immune recognition of primary melanomas.

Base Sequence↗

Acral-lentiginous naevus of plantar skin.

In a consecutive series of 165 plantar naevi, a group of 36 benign naevi with sufficiently distinctive histopathological features to justify their classification as a special entity, here designated acral-lentiginous naevus, was identified. The main morphological features distinguishing the acral-lentiginous naevi from other acral non-lentiginous naevi are: elongation of rete ridges, continuous proliferation of melanocytes at the dermo-epidermal junction, presence of single scattered melanocytes, or less commonly small clusters, within the upper epidermis, poor or absent lateral circumscription, melanocytes with abundant pale cytoplasm and round to oval, sometimes hyperchromatic, nuclei and prominent nucleoli present at the dermo-epidermal junction. Some histological features of acral-lentiginous naevi are similar to those of dysplastic naevi: however, anastomosing rete ridges, cytological atypia and well-formed lamellar fibroplasia are absent. The histopathological criteria to distinguish these naevi from melanoma are: the lack of pagetoid lateral spread, the absence of mitotic activity in the deep dermal component and the evidence of dermal naevocytic differentiation. The identification of this benign acral naevus, that we have identified as the benign counterpart of acral lentiginous melanoma, is important in order to avoid misdiagnoses and consequent under- or over-treatment of doubtful pigmented lesions of acral skin.

Diagnosis, Differential↗

In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. III. CCD camera-based reflectance imaging.

Reflectance spectroscopy, which allows an objective evaluation of the color of surfaces, has recently been proposed as a useful tool to discriminate cutaneous melanoma from other pigmented cutaneous lesions. A novel spectrophotometric system based on the use of a charge coupled device camera provided with a set of interference filters has been developed to acquire images of cutaneous pigmented lesions at selected wavelengths ranging from 420 to 1040 nm. For each filter, an image was captured, digitized by a frame grabber and stored in a personal computer to perform off-line data handling. Reflectance images were acquired of 22 cutaneous pigmented lesions including melanoma and dysplastic, compound and junctional nevus. From each spectral image, three parameters, i.e. mean reflectance, variegation index and lesion area; were derived at the corresponding wavelength. The wavelength dependence of the three parameters was significantly different when melanoma was compared to the other investigated lesions. Although preliminary, our results suggest that telespectrophotometry gives useful information and could be utilized as an aid in the clinical diagnosis of cutaneous pigmented lesions.

Humans↗

Right subclavian artery aneurysm and coarctation of the aorta.

A patient, diagnosed with coarctation of the aorta at the age of 59, was found to have a pulmonary mass in his right upper lobe. A chest scan and digital intravenous arteriography revealed a right artery subclavian aneurysm. Such an unusual association is described.

Aneurysm↗

N-RAS mutations and susceptibility to lymphokine-activated killer (LAK) cells in human melanoma.

RAS oncogene expression has been reported to affect several biological features of rodent tumours cells, including lysability by activated natural killer cells. In order to examine whether expression of mutated RAS genes in human melanoma cells alters their susceptibility to lysis by LAK cells, seven melanoma lines were assessed for the presence of Ki- and N-RAS genes bearing all possible mutations at codons 12, 13 and 61. A panel of 21 clones deriving from the metastatic lesion Me665/2, which had a Gln-->Arg substitution at codon 61 of N-RAS (N-RAS/61+), were also examined. Melanoma cells and clones were used as targets of allogeneic LAK in a 4-h 51Cr-release assay. LAK showed a higher lysis on melanoma lines and clones harbouring a mutated RAS compared with counterparts bearing no RAS mutations. In addition, LAK-mediated lysis drastically decreased on Me665/2 sublines progressively selected by exposure to LAK. This loss was paralleled by a reduction or even disappearance of N-RAS/61+ mRNA signal in Me665/2 sublines. To evaluate whether N-RAS could directly modulate LAK susceptibility to lysis, N-RAS/61+ gene was transfected in two N-RAS wild type (N-RAS/61-) 665/2 melanoma clones by a cosmid vector. In contrast to the high lysability of melanoma cells constitutively expressing the mutationally active N-RAS oncogene, N-RAS/61+ transfectants did not show a consistent high lysability by LAK, compared with some control pSV2neo transfectants.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Childhood cutaneous melanoma.

Seventeen consecutive patients no older than 14 years with cutaneous melanoma were observed from 1975 to 1991 at the Istituto Nazionale Tumori, Milan; this series represented 0.8% of all cutaneous melanomas observed at the Institute during this period. Ten were males and seven females. Nine lesions arose on limbs, seven on the trunk, and one on the head and neck area. Reexamination of the clinical records suggests that childhood melanoma may present with unusual characteristics such as unusual appearance of the primary lesion and lack or scarcity of pigmentation. At first observation ten patients had stage I disease nine underwent surgery alone while in one surgery was performed in combination with regional lymph node dissection and chemotherapy. All the stage II patients underwent excision of the primary lesion and lymph node dissection. One of the 2 stage III patients received lymph node dissection only, and the other no treatment. Analysis of this series of 17 cases does not indicate that cutaneous melanoma in children is more aggressive than in adults. It is stressed that, although rare, the physician should be aware that cutaneous melanoma may occur in prepuberty.

Adolescent↗

Acral lentiginous melanoma. A histological type without prognostic significance.

BACKGROUND: Acral lentiginous melanoma (ALM) is reported to have a poorer prognosis than melanomas of other histotypes. OBJECTIVE: The purpose of this paper is to verify if ALMs, per se, have a more aggressive behavior or if the poorer prognosis of these patients is due to a later diagnosis. METHODS: Clinical charts of 165 patients with acrally located melanoma were reviewed as well as all histological slides. In all patients, histotype, Clark's level, Breslow thickness, pigmentation, presence of ulceration, and regression were reported. Mitotic index, vascular invasion, and microscopic satellitosis were also determined. Survival of the 64 patients with ALM was compared with survival observed in the remaining 101 acral (nonlentiginous) melanomas. RESULTS: Melanoma localized at acral sites constitute 8.9% of the 1845 patients with melanoma treated at our Institute from 1975 to 1990. All were Caucasian, 57 were males, and 108 females. Out of the 165 patients with this localization, 64 (38.8%) were classified as ALM. Disease-free and overall survival of the 64 ALM patients were not different at a statistically significant level compared with the areas observed in the other acral nonlentiginous melanoma. CONCLUSION: The survival difference between ALM and other histological types is due to a later diagnosis and not to a more aggressive behavior of ALM.

Disease-Free Survival↗

Endoscopic treatment of polyps in the resected stomach.

Between 1974 and 1992, at the Department of Diagnostic and Surgical Endoscopy of Istituto Nazionale Tumori, in Milan, 27 patients with resected stomach and suffering from epithelial polyps of the gastric stump (10 lesions) and/or anastomosis (25 lesions), were endoscopically treated using electroresection (13 cases), electrocoagulation (2 cases), combined methods (electroresection plus Nd:YAG photocoagulation) (1 case) and biopsy forceps (19 cases). Complications occurred in 4 cases and consisted of hemorrhage. Seven patients developed 15 recurrences. Endoscopic treatment of polyps in patients with resected stomach is a safe and effective treatment, considering the low rate of complication.

Adult↗

[Carcinoid tumor. An analysis of 131 cases].

We would like to describe the characteristics of affection by carcinoid tumor in our surroundings. In so doing, we have reviewed the clinical histories of the 131 cases of carcinoid tumor diagnosed in our center between 1972 and 1990. The incidence has been 0.7 cases per 100,000 inhabitants per year. The age at diagnosis is from 8 to 88 years, and the proportion of men to women is practically 1. The most common locale affected the appendix (54 cases) followed by the bronchials (46 cases). The most common clinical presentation has been casual discovery and in the bronchials, in addition to hemoptysis and pneumonia. Carcinoid syndrome was found in only 4 cases, and of 17 determinations of indole acetic 5-hydoxi acid, only 2 resulted pathological. There were four cases of hepatic metastasis and two deaths related with the tumor.

Adolescent↗

Perinodular injection of thymopentin (TP5) in cutaneous and subcutaneous metastases of melanoma.

The potential therapeutic efficacy of TP5 in patients with cutaneous and subcutaneous metastases of melanoma was tested in a double-blind study comparing the drug and placebo injected perinodularly. Of the 47 nodules present in the 16 patients treated with TP5, 24 showed a measurable response, whereas only one out of 15 nodules in patients treated with a placebo showed a minor response (P = 0.02). In two patients treated with TP5 a response of two nodules not perinodularly injected was also observed. Sclerosis, CD45RO+ cells and MIB 1- cells were more frequently observed in nodules treated with TP5 than with placebo. (P = 8 x 10(-4); 0.03 and 0.01, respectively). Evaluating the trends of these findings in nodules treated with placebo; with TP5-treated, non-responding nodules; or with TP5-treated, responding, a positive trend was observed for sclerosis and CD45RO+ cells (P = 5 x 10(-4) and 2 x 10(-3), respectively) and a negative one for MIB 1 cells (P = 2 x 10(-3)). These preliminary data suggest that lymphoid cells associated with nodules regression are activated large lymphocytes (CD45RO+ and CD3-). Sclerosis might be interpreted as the final morphologic event, and reduction of proliferative activity (MIB 1- cells) as the consequence of cytolytic action.

CD3 Complex↗

[123I]IBZM uptake in metastatic melanoma.

In this report we describe our experience with [123I]IBZM ([123I]-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolid inyl)methyl] benzamide), used to image the lesions in a female patient affected by metastatic melanoma. Marked uptake of [123I]IBZM in an area corresponding to a palpable lymph-nodal mass was observed in images collected 2 and 5 hours after i.v. tracer administration. Tumour to non-tumour ratios evaluated on planar maps were found to be 2.04 and 2.35, respectively. Surgical excision and histological examination of inguinal nodes confirmed the presence of melanoma lymph-nodal metastases. Although scintigraphy with radiolabelled [123I]IBZM is widely used for neuro-psychiatric disorders, we have found no reports in the literature of any application of this tracer in oncology. Even if the biological bases underlying the findings reported here remain unclear (although they are probably related to the neural crest origin of the melanocytes), the quality of imaging found suggests that this tracer may provide a new diagnostic tool for the imaging of melanoma tumours.

Aged↗