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Biomedical subjects

M Vaglini

Publications and source records attributed to M Vaglini.

At least 37 records · Page 2Linked to original sources

Seven years experience with hyperthermic perfusions in extracorporeal circulation for melanoma of the extremities.

One hundred forty patients affected by high risk or locally advanced melanoma of the extremities were submitted to hyperthermic perfusion in extracorporeal circulation at the National Cancer Institute of Milan, Italy. Using adequate temperature and drug dosage, we increased survival of stage IIIA patients from 8-15% to 51% and stage IIIAB patients from 7-8% to 35%, and good local control was achieved in stage IV patients. A comparison was made with 297 patients with similar disease treated in a previous period in this institute with conventional therapies such as surgery with or without chemotherapy. In stage IIIA patients we obtained 51% overall survival at 5 years in perfused cases, whereas survival in the series with conventional treatment reached 16%. Similarly, in stage IIIAB patients we observed 34% (perfused) versus 16% (conventional treatment) survival. There are still no data available for high-risk stage I, in which perfusion is employed as an adjuvant treatment.

Antineoplastic Agents↗

Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma.

The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant melanoma biopsies have been investigated by a short-term assay based upon the inhibition of 3H-thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42 degrees C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43 degrees C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5 degrees C), with only a slight increase in the frequency of synergy at 42 degrees C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors at 42 degrees C as a function of drug concentration.

Antineoplastic Agents↗

Cancer patients' lymphocytes contain CD3+ CD4+ cells that proliferate in response to autologous tumor cells in the presence of exogenous low-dose interleukin-2 and autologous accessory cells.

To see whether cancer patients possess CD3+ CD4+ lymphocytes able to proliferate in response to autologous tumor cells (Auto-Tu), this lymphocyte subset was isolated either by positive or negative selection, both methods resulting in highly enriched CD4+ populations. Unseparated and isolated CD3+ CD4+ lymphocytes were then assayed for proliferating activity in the presence or absence of various amounts of Auto-Tu, with or without recombinant interleukin-2 (IL-2) (1.5-15 U/ml) and DR+ adherent cells or E- lymphocytes as autologous accessory cells (Auto-AC). Isolated CD3+ CD4+ lymphocytes were stimulated by Auto-Tu alone in only 1 out of 12 cases. CD3+ CD4+ cells failed to proliferate significantly in response to low doses of IL-2 alone but the addition of Auto-Tu caused stimulation in 8 out of 12 cases (67%). The further addition of Auto-AC to Auto-Tu + IL-2 resulted in enhanced response of isolated CD3+ CD4+ lymphocytes in 6 out of 8 cases tested. When reactivities to Auto-Tu in the presence of IL-2 and IL-2 + Auto-AC were considered together, positive responses of CD3+ CD4+ lymphocytes were seen in 11 out of 12 cases (92%). On the other hand, unseparated lymphocytes were stimulated by Auto-Tu alone in none out of 12 cases. Unseparated lymphocytes, however, responded to IL-2 in 11 out of 12 cases; such a response was increased by the addition of Auto-Tu in only 2 cases. Moreover, the IL-2 proliferation of unseparated lymphocytes was suppressed in 4 and in 3 out of 12 cases tested when Auto-Tu or Auto-Tu + Auto-AC were added respectively. These data indicate that lymphocytes of cancer patients contain CD3+ CD4+ cells that are usually unable to proliferate in response to Auto-Tu only. This proliferation, however, occurs when low doses of exogenous IL-2 are present and can be further amplified by the addition of Auto-AC. No response of CD4+ cells is observed in the presence of DR+ Auto-AC + IL-2 except in 2 out of 7 cases tested (28%), suggesting an Auto-Tu-restricted reactivity of CD3+ CD4+ lymphocytes in the majority of cases.

Antigen-Presenting Cells↗

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↗

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↗

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↗

Hyperthermic antiblastic perfusion with DTIC in stage IIIA-IIIAB melanoma of the extremities.

The aim of this paper is to evaluate the effectiveness of DTIC when employed at a local level in hyperthermic antiblastic perfusion (HAP) for stage IIIA-IIIAB melanoma patients. Twenty-seven consecutive patients have been treated at the National Cancer Institute of Milan from October 1983 to June 1985. All the patients were submitted to HAP at 40 degrees for 60' with DTIC at the dosage of 2.5 g/m2 [corrected] for lower extremities and 1.5 g/m2 [corrected] for upper extremities. We observed a complete local response in three patients and a partial local response 50% in seven patients, 10 patients has a response less than 50% and 4 patients did not show any response. After surgical removal of the residual tumor when possible, 14 patients are alive without detectable disease while 11 are alive with disease and two dead for progression. No serious complications were observed. These data indicate that DTIC seems able to obtain in HAP, results superimposable to L-PAM without any significant toxicity.

Adult↗

BANS. A cutaneous region with no prognostic significance in patients with melanoma.

Data of 769 Stage I melanoma patients treated from 1967 to 1974 by the W.H.O. Melanoma Group centers were analyzed. The mean follow-up period was 10.3 years. Of the 769 patients (239 males, 530 females), 133 had a primary in the BANS region. The observed ten-year actuarial survival was 54.8% for the 133 BANS patients and 54.9% for the remaining 636. Multivariate analysis showed that thickness was the most important prognostic factor (P = 10(-9]; ulceration and sex were also found to be significantly related to survival (P values were 5 X 10(-4) and 10(-5), respectively). The other criteria were no longer significant when adjusted by these three. In particular, the BANS region had a P value of 0.6. To evaluate the effect of BANS in thin melanoma, a subgroup of 152 patients (29 BANS, 123 other) with primary thickness between 0.76 and 1.69 mm was studied. Multivariate analysis showed that no criteria are significantly associated with prognosis of these patients. Observed actuarial survival rate for BANS patients was 69.2% and for the remaining 123, 66.7%. The number of deaths was 8/29 and 27/123. The BANS region does not appear to be of importance in the prognosis of Stage I melanoma patients.

Analysis of Variance↗

Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities.

From February 1982 to December 1983, 42 patients affected by neoplasms of the limbs were treated at the Istituto Nazionale Tumori of Milan by hyperthermic antiblastic perfusion in extracorporeal circulation at the temperature of 40-41 degrees C for 1 h. Thirty-two were affected by melanoma, 4 by osteogenic sarcoma, 2 by squamous-cell carcinoma, 1 by liposarcoma, 1 by hemangiopericytoma, 1 by clear-cell sarcoma and 1 by Kaposis's sarcoma. As regards the immediate response, a complete plus partial remission rate of 88% without any major complication was obtained. The follow-up period is too short for any considerations about overall survival. However, because of these good clinical results we consider this method able to locally control the evolution of neoplasms of the extremities, allowing in many cases a limb salvage.

Adolescent↗

Limb-salvage procedure in two patients with spindle cell carcinoma of the lower extremities using isolation perfusion.

Two patients with extensive squamous cell carcinoma of the lower extremities, candidate for demolitive surgery, were treated by hyperthermic antiblastic perfusion in extracorporeal circulation. The temperature reached was 41 degrees C and the drug used was methotrexate at the dosage of 500 mg. Radical excision of the ulcer was possible in the 2 patients. Both tumors underwent extensive necrosis, and histology done 1 month after perfusion on surgical specimens showed limited areas of residual malignancy. These 2 patients suggest that hyperthermic antiblastic perfusion may be a limb salvage procedure in the multimodal management of extended squamous cell carcinoma of the extremities.

Aged↗

Hemostatic alterations are unrelated to the stage of tumor in untreated malignant melanoma and breast carcinoma.

A study of hemostatic variables was carried out in 80 untreated patients with breast adenocarcinoma or malignant melanoma, chosen as examples of tumors that can be accurately staged for localization or spread. The most marked abnormalities were high levels of clotting factors V and VIII, plasminogen, von Willebrand factor and fibrogen-fibrin degradation products. These abnormalities occurred in both types of tumors, albeit slightly more markedly in melanomas, and were also present in localized tumors. Our data indicate that in tumors, abnormalities of the hemostatic system are an early phenomenon unrelated to the presence of widespread malignancy.

Adenocarcinoma↗

Prospective randomized trial in advanced malignant melanoma with cis-platinum, vindesine, and etoposide vs. cis-platinum, vindesine, and lomustine.

Thirty-seven consecutive patients with disseminated malignant melanoma and previously untreated with chemotherapy were randomly allocated to receive vindesine, cis-platinum, and etoposide (Regimen A) or vindesine, cis-platinum, and lomustine (Regimen B). In 31 evaluable patients, Regimen A induced an overall response rate of 31% and a complete response rate of 6%; with Regimen B the corresponding findings were 20% and 20%, respectively. The median duration of complete response was 12 months with both regimens and the comparative median total survivals were 8 and 6 months, respectively. In no case was toxicity so severe to require treatment discontinuation, and the major dose-limiting side effect was myelosuppression, especially in the patients treated with Regimen B. Present results confirm once more the limited activity of drugs and regimens presently utilized in the treatment of advanced malignant melanoma.

Adult↗

HLA antigen frequencies in malignant melanoma patients. A second study.

Two groups of malignant melanoma (MM) patients were considered: the group of 140 patients previously published and a new one of 58, both typed for HLA-A, -B and -C antigens at the Istituto Nazionale Tumori of Milan. The control group consisted of healthy blood donors not related to the patients. Only the HLA-Bw35 antigen frequency was significantly decreased in both groups of patients. To investigate the HLA-A and -B blanks, 62 MM patients and 90 healthy controls, who showed non-homozygotic blanks when they were firstly HLA typed, volunteered to repeat the HLA typing three or more times in a 2-year period. A significant increase in both HLA-A and -B blanks in the patients as compared to controls was noticed (p = 3 X 10(-4) and 3 X 10(-5), respectively). In the future, attempts should be made to correlate the HLA antigen and blank frequencies with the evolution of the disease and, also, to verify the hypothesis that the HLA-Bw35 antigen may be an associated resistance factor against the tumor.

Female↗

Prognosis of skin melanoma with regional node metastases (stage II).

566 stage-II melanoma patients treated at the National Cancer Institute of Milan, Italy, were analyzed to evaluate the prognosis. Among the criteria considered, four were significantly associated with survival when considered as single factors: growth pattern, levels of invasion, the number of involved lymph nodes, and the extent of metastatic growth. As regards growth pattern, the observed 5-year survival rates were 41.9% for superficial spreading melanoma and 20.5% for nodular melanoma (P = 10(-3)). As regards levels, the 5-year survival rates were as follows: level II, 20.9%; level III, 33.1%; level IV, 43.2%; level V, 10.2% (P = 10(-3)). Patients with a partial node metastasis had 64.5% 10-year survival, while those with extension beyond the capsule had 32.6% 10-year survival (P = 10(-9). Patients with one metastatic node had 43.4% 10-year survival, and patients with three or more positive nodes had 26.0% 10-year survival (P = 10(-9)). Multifactorial analysis shows that growth pattern and extent of node metastases significantly affect survival (P = 10(-2) and P = 10(-4), respectively) while the number of involved nodes turns to borderline P-value (0.051) and the levels are no longer significant (P = 0.4).

Adolescent↗

Regional perfusion at high temperature in treatment of stage IIIA-IIIAB melanoma patients.

The results obtained with isolation perfusions in stage IIIA-IIIAB melanoma patients, performed at 42.5-43 degrees C for 2.5 h, are reported. These temperatures and perfusion times were chosen on the basis of experimental data in animal models and in vitro. The clinical results were impressive, but the high percentage of complications and the high cost from a social and human point of view make this experience negative with regard to its clinical applicability, at least with such a high temperature and long perfusion time.

Adult↗

HLA complex and familial malignant melanoma.

Six families with familial malignant melanoma (FMM) were HLA-A, -B, and -C typed to ascertain whether or not FMM would segregate with the HLA complex. The HLA-B12 antigen was present in five of the six families. In three families the HLA-FMM linkage could be analyzed: linkage was possible in two but not in the third. These findings suggested that two types of FMM may exist: a more frequent type (five cases) that apparently segregates with the HLA complex and another (one case) that does not segregate with the HLA complex. Moreover, a factor included in the HLA region or another factor linked to it may have played an important role, in five of the six families, in FMM pathogenesis, whereas in the sixth family its role may have been performed by some other factor. These findings are consistent with the hypothesis of two complementary factors (one of which was included in the HLA complex) for the promotion of FMM with dominant inheritance and high penetrance.

Female↗