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Biomedical subjects

N Cascinelli

Publications and source records attributed to N Cascinelli.

At least 109 records · Page 6Linked to original sources
PubMed1989

Early presence of activated ('exhausted') platelets in malignant tumors (breast adenocarcinoma and malignant melanoma).

To evaluate whether or not the finding of platelet activation in patients with tumors is related to the stage of malignancy, a study of biochemical markers indicative of the presence of circulating activated ('exhausted') platelets was carried out in 95 untreated patients with breast adenocarcinoma or malignant melanoma, localized or spread to regional lymph nodes with no detectable distant metastasis. These tumors were chosen as examples of tumors which can be accurately staged for localization or spread, and as examples of mucin-secreting tumors (breast adenocarcinoma) or neuroectodermic tumors (malignant melanoma). Results were compared with those for 26 patients with benign breast disease, 23 blood donors and 50 hospital workers. The most frequent abnormalities were low levels of intraplatelet ADP and 5-hydroxytryptamine and high ATP/ADP ratios. Although these abnormalities occurred with both types of tumor, they were more frequent and marked for melanomas and breast carcinomas spread to regional lymph nodes. Our data indicate that the presence of exhausted platelets is an early finding in patients with malignant tumors.

Adenocarcinoma↗
PubMed1989

Increasing incidence of cutaneous melanoma, ultraviolet radiation and the clinician.

Incidence of melanoma is certainly rising all over the world and this observation has been related to a more frequent and prolonged exposure to the rays of the sun. The authors critically review pertinent literature and conclude that descriptive epidemiology of melanoma does not give survival trends and does not support the claim that melanoma is ultraviolet (UV) dependent. Analytical epidemiology has not reached a consensus on this aspect. Experimental data available are also difficult to interpret because there are consistent differences of susceptibility to UV among different animals, among lamps used and methods of measuring employed in various laboratories. Information available shows that the maximal relative biological activity of UV in humans is at about 305 nm. This evaluation greatly depends on (1) thickness of the skin, (2) the quantity and quality of secretions that cover the skin, (3) cleanness of the skin, (4) the latitude, (5) the weather, (6) the hour of the day and (7) the presence of chemical carcinogens in the air and on the skin. The authors stress the importance of the criteria of clinical diagnosis recently introduced in clinical practice and higher public awareness as the causes of the increasing incidence of melanoma.

Animals↗
PubMed1988

HLA antigens in familial and sporadic cutaneous melanoma.

One hundred and twenty-four subjects belonging to 25 families, 51 with familial malignant melanoma (FMM), and 186 subjects belonging to 41 families, 41 with sporadic malignant melanoma, were typed for the HLA A, B, C and DR loci of the HLA system. There was the same statistically significant difference in the frequency of the haplotype A9, B35, Cw4 between each group of patients and the respective healthy relatives (p = 0.01, p = 0.01 and p = 4 x 10(-3), respectively). Moreover, the higher frequency of the haplotype A9, B35, Cw4 in the healthy members of the FMM families (42.46%) compared with the healthy members of the SMM families (23.44%) indicates that in the latter group other individuals are at risk for the disease. Furthermore, the different frequency of haplotypes B5, DR5 and B5, Cw1 suggest that differences exist between the two groups of healthy relatives. These observations confirm that the HLA region is involved in the etiology of malignant melanoma.

Gene Frequency↗
PubMed1988

A new procedure for large scale production and freezing of lymphokine activated killer (LAK) cells to be used in adoptive immunotherapy of cancer.

A new procedure for activation of peripheral blood lymphocytes (PBL) with recombinant interleukin 2 (rIL2) is described. PBL obtained by leukapheresis were subjected to NH4Cl (ACK) treatment to clear erythrocyte contamination; Ficoll separation was not performed. PBL were subsequently seeded in 10-floor multitrays (Cell FactoryTM, CF), gasified and incubated at 37 degrees C for 3-4 days in a humidified 5% CO2 atmosphere. This procedure achieved an activation (evaluated as cytotoxicity and proliferation) comparable with that obtained by culturing PBL in small flasks. Optimal activation of PBL was achieved in CF even in the presence of granulocyte contamination of up to 40%. It was also possible to freeze, thaw and recover most of the frozen cells and their cytotoxic activity. With this procedure therefore large quantities of lymphokine activated killer cells (LAK) can be easily produced to be used in adoptive immunotherapy trials.

Blood Preservation↗
PubMed1988

Monoclonal antibodies MBr1 and MBr8 as predictors of response to oophorectomy in advanced breast cancer.

The response to oophorectomy in 40 patients with advanced breast cancer was evaluated as a function of the presence or absence of the antigens recognized by the monoclonal antibodies MBrl, MBr8, and MOv2 on the cell surface of the primary tumor. Two groups (20 patients alive 5 years after oophorectomy and 20 patients who died within 5 years) were evaluated. These groups had a) the same distribution of lymph node status, diameter of the primary, and the presence of estrogen receptors at the time of first treatment and b) a comparable extent of the disease at the time of oophorectomy. The frequency of complete response after oophorectomy was significantly higher in patients whose tumors did not express the antigens recognized by antibodies MBrl and MBr8. Fourteen of the 22 patients with tumors not reacting with MBrl and 11 of the 18 negative to MBr8 had a complete response. There was no correlation with response and the monoclonal antibody MOv2. Both MBrl and MBr8 were present in 11 patients and both were absent in another 11. The simultaneous absence of the two antigens was related to the highest complete response rate (9 out of 11 patients).

Antibodies, Monoclonal↗
PubMed1988

In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2.

A phase-I study of the recombinant, non-mutagenized interleukin 2 (rIL2, BioleukinTM) was performed in 12 melanoma patients (Pts). From 100 to 800 micrograms/m2 of rIL2 were administered by i.v. bolus injection, TID for 4-8 days. Side-effects included fever, malaise, low serum K+ and Ca++ values, electrocardiographic abnormalities, leukopenia and thrombocytopenia. No major organ toxicity and no significant fluid retention were observed at the administered doses. Treatment induced a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound (2-6 times the pre-treatment values), 24-48 hr after rIL2 discontinuation. PBL obtained between the 5th treatment day and the 2nd post-treatment day showed: (a) enhanced proliferation (II/12 Pts) with stimulation indexes of 6-52; (b) increased cytotoxicity against autologous tumor cells (2/2 Pts), allogeneic melanomas (5/7 Pts), the Daudi (5/6 Pts) and K562 cell lines (7/12 Pts); and (c) increased expression of IL2 receptors (8/12 Pts) and of DR antigens (6/12 Pts). Lymphocytes collected 1-2 days after treatment and activated in vitro with rIL2 showed a more rapid development of tumor cytotoxicity, with an earlier loss of activity. Spontaneous proliferation, autologous or allogeneic tumor cytotoxicity and expression of IL2 receptors obtained after in vivo treatment with rIL2 were significantly weaker than those induced during in vitro stimulation. No major objective responses were detected in these patients.

Antigens, Surface↗
PubMed1988

Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm.

Although wide surgical excision is the accepted treatment for thin malignant melanomas, there is reason to believe that narrower margins may be adequate. We conducted a randomized prospective study to assess the efficacy of narrow excision (excision with 1-cm margins) for primary melanomas no thicker than 2 mm. Narrow excision was performed in 305 patients, and wide excision (margins of 3 cm or more) was performed in 307 patients. The major prognostic criteria were well balanced in the two groups. The mean thickness of melanomas was 0.99 mm in the narrow-excision group and 1.02 mm in the wide-excision group. The subsequent development of metastatic disease involving regional nodes and distant organs was not different in the two groups (4.6 and 2.3 percent, respectively, in the narrow-excision group, as compared with 6.5 and 2.6 percent in the wide-excision group). Disease-free survival rates and overall survival rates (mean follow-up period, 55 months) were also similar in the two groups. Only three patients had a local recurrence as a first relapse. All had undergone narrow excision, and each had a primary melanoma with a thickness of 1 mm or more. The absence of local recurrence in the group of patients with a primary melanoma thinner than 1 mm and the very low rate of local recurrences indicate that narrow excision is a safe and effective procedure for such patients.

Adult↗
PubMed1988

Anti-melanoma monoclonal antibody 225-28S: evaluation of toxicity in man.

To investigate possible undesirable effects due to the intravenous administration of a reagent of a xenogenic nature (monoclonal antibody 225-28S) in man, a toxicologic study was carried out on 85 patients with metastatic cutaneous melanoma. Two reagents were tested in this study: purified monoclonal antibody (MoAb) 225-28S and its F(ab')2 fragment. Purified MoAb was labelled with 131I and F(ab')2 fragment with 131I, or 123I, or 111In or 99Tc. The quantity of MoAb or F(ab')2 injected ranged from 14 to 750 micrograms, and the specific activity from 37.0 to 2116.4 MBq/mg. The total radioactivity injected varied from 25.9 to 891.7 MBq/mg. In addition to a careful clinical examination, the following tests were done to monitor possible adverse effects: blood glucose, azotemia, RBC, WBC, platelet count, serum creatinine, creatinine clearance, plasma electrolyte levels, serum proteins, albumin/globulin ratio, serum bilirubin, SGOT, SGPT, gamma GT, and CPK. These tests were done before the injection and on days 7 and 14. No patient experienced adverse general effects like fever, nausea, vomiting or allergic reactions. None of the aforementioned hematometric and biochemical tests showed significant variations compared with the initial values. It is concluded that a single injection of these reagents at the dosages tested is completely atoxic.

Adolescent↗
PubMed1987

A phase I study of recombinant interleukin 2 in melanoma patients. Toxicity and clinical effects.

Toxicity and clinical effects of a new brand of recombinant interleukin 2 (rIL2, BioleukinTM, Biogen, Geneva) were evaluated by a phase I study in 12 patients with stage III melanoma. Escalating doses from 100 micrograms/m2 to 800 micrograms/m2 were administered thrice a day with bolus injections given via a peripheral venous catheter for up to a maximum of 7 days. All patients showed malaise, fever and chills and mild gastrointestinal side effects. A modest electrolyte imbalance (hypocalcemia and hypokalemia) was detected in all 12 patients. Renal toxicity as judged by serum creatinine was not observed, and hepatic toxicity was moderate with the possible exception of one patient who had an unclear previous history of liver dysfunction. Mild, transient leukopenia was found in several patients, whereas thrombocytopenia developed in 4 patients; no anemia was observed. Cutaneous rash was seen in half of the patients treated. Fluid retention was minimal, with a weight gain associated to treatment that never exceeded 10% of pretreatment body weight. Electrocardiographic alterations developed in 2 patients in the form of ventricular and supraventricular extrasystoles. In 2 patients given the highest dose of rIL2, a significant reduction in transfer lung factor for carbon monoxide was seen, indicating alterations in pulmonary functions. Other dose-related toxicities were thrombocytopenia and malaise. All side effects disappeared 2-3 days after the end of rIL2 administration. No major responses were seen in association with the 4-8 days of treatment given in this study.

Adult↗
PubMed1987

Topical administration of tetrasodium-meso-tetraphenylporphinesulfonate (TPPS) and red light irradiation for the treatment of superficial neoplastic lesions.

In photodynamic therapy, systemic administration of photosensitizing agents induces cutaneous photosensitization in patients. This side-effect can be avoided by topical administration of the agents when only surface lesions are involved. A hydroalcoholic solution of tetrasodium-meso-tetraphenylporphinesulfonate (TPPS) containing Azone, a percutaneous penetration enhancer, was investigated to evaluate its photosensitizing potential in the treatment of 33 primary and recurrent neoplastic lesions of the skin. A complete remission was obtained of lesions with clinical thickness of less than 2 mm. Treatment effectiveness depends on both light and drug penetration through skin. Further studies are in progress to optimize treatment parameters.

Administration, Topical↗
PubMed1987

Preliminary clinical studies with PDT by topical TPPS administration in neoplastic skin lesions.

Cutaneous photosensitization by topical administration of a porphyrin derivative has been previously reported from experimental studies. Preliminary clinical trials performed at the National Cancer Institute of Milan in the last six months have confirmed the feasibility of treating skin lesions by topical application of photosensitizers. Fourteen cases of basal cell carcinoma were treated by local administration of tetraphenylporphinesulphonate (TPPS), vehicled by azone. Later, the tumor was exposed to a wavelength of 630 nm from a dye laser. We noted complete remission, as documented by biopsies, in all tumors, with clinical thickness less than 2 mm, whereas partial remission was obtained in tumors with clinical thickness more than 2 mm. Our experience suggests the possibility of a routine treatment by this method for flat basal cell carcinoma and pre-malignant lesions, with remarkable advantages to conventional therapies. Our results have to be confirmed by increasing the number of cases and length of follow up; our short follow up does not allow us to make definitive claims regarding this therapy.

Administration, Topical↗
PubMed1987

Prognosis of breast cancer with axillary node metastases after surgical treatment only.

Out of 753 patients with breast cancer treated with radical mastectomy from 1968 to 1970 at the National Cancer Institute of Milan, Italy, 308 had histologically proven positive nodes. The number of positive nodes was not dependent on the location of the primary tumour, its diameter and the patient's age. Extracapsular invasion was related to the number of positive nodes at a statistically significant level: P value 2 X 10(-9). Survival was influenced by the number of positive nodes and extension of metastases beyond their capsule and age. Each of these criteria had an independent impact on survival. Three subgroups with different prognosis were identified in patients older than 40: (a) with a single involved node and 69.9% 10 year survival rate, (b) patients with two or more nodes with metastatic deposit still confined within node capsule and 47.4% 10 year survival rate, (c) patients with two or more involved nodes and extracapsular invasion and 25.3% 10 year survival rate. In patients younger than 40 no subgroup was identified: this group had an intermediate 10 year survival rate (50.9%). The authors conclude that there is a need (a) of re-consideration of the prognosis of patients with positive nodes and (b) to agree on the definition of "high-risk patients".

Adult↗