Evaluation of phagocytic-activity in neoplastic patients treated with subcutaneous recombinant IL-2.

Immunostimulating and immunosuppresive events have been noted during rIL-2 immunotherapy and cell-mediated immune deficiencies have been reported in the neutrophil and monocyte functions, determining a high incidence of infections in patients during intravenous rIL-2 treatment. The phagocytic activity of monocytes/macrophages and granulocytes was evaluated in 10 advanced solid tumor patients treated with subcutaneous rIL-2. Several indirect parameters of phagocytosis were also considered, such as Neopterin, Beta2 microglobulin, IL-2 soluble receptor, and the C3 and C4 fractions of the complement system. A decreased phagocytosis was demonstrated after subcutaneous rIL-2 administration together with an increase of indirect parameters of granulocyte/macrophage activity. Therefore, cellular activation does not seem to correspond to actual phagocytosis which is probably due to IL-2-induced secondary cytokines or to rIL-2 inhibitory effects.

Subcutaneous ril-2 in advanced melanoma and kidney carcinoma.

The aim of the present study was to verify the efficacy and tolerability of a treatment protocol using subcutaneous administration of rIL-2. Eighteen patients with metastatic disease were treated: 10 with renal carcinoma and 8 with malignant melanoma. The drug was administered as follows: 9 million UI/mq twice daily for two days followed by 1.8 million UI/mq twice daily for five days/week for six consecutive weeks. Of the 15 patients evaluated for clinical response, all completed treatment without rIL-2 dose modifications. No complete response was obtained. One patient with malignant melanoma and 1 with renal carcinoma (13%) had partial response (soft tissue and lymph nodes respectively) which lasted 3 and 4 months. Six patients with renal carcinoma and 3 melanoma patients had stable disease (60%) which lasted 6 months (median). Toxicity was moderate and spontaneously reversing after stopping treatment. Haemato-immunological modifications and pharmacokinetic study of this modality of rIL-2 treatment were also examined.

Comparison of nuclear matrix protein 22 and bladder tumor antigen in urine of patients with bladder cancer.

Recently, two new tumor markers for bladder cancer have been introduced: NMP22 test and BTA TRAK assay. This study was designed to evaluate the urinary values of these two proteins using quantitative enzyme immunoassays in well microplates. Urine samples from 47 healthy subjects, 26 with benign genitourinary disorders and 109 patients with a histological diagnosis of bladder cancer were collected. The specificity, the positive predictive value, the negative predictive value and the efficiency were established for NMP 22 and BTA, and the cut off values were fixed at a specificity of 95% in the benign disease group (12 U/ml and 23 U/ml respectively). We observed a very high concordance between the two urinary tumor markers (73%), although the overall sensitivity of BTA in bladder cancer patients seems to be better than that of NMP22 (62% vs 54% respectively), especially in the superficial disease group (36% for BTA and 14% for NMP22).

Serum levels of ceruloplasmin, properdin factor B and copper in lymphoma patients.

The serum levels of Ceruloplasmin (CER), Properdin Factor B (PFB) and Copper (CU) were evaluated in a series of 40 patients with Hodgkin's Disease and 46 patients with non-Hodgkin's lymphoma. Concentrations of CER and PFB were determined by rate nephelometry and CU concentrations by the bathocuproine colorimetric method. The results obtained demonstrated that CER, together with the well documented CU, can be used for monitoring Hodgkin's Disease.

Total circulating B lymphocyte abnormalities in a primary cerebral localization of non-Hodgkin lymphoma: a case report.

The authors describe a case of primary central nervous system lymphoma in a 43-year-old male. Interest in this rare form of B-lymphocyte non-Hodgkin's lymphoma is due to its increasing incidence in the last decade, especially in immunodeficient patients. Extraneural involvement was excluded by staging examinations: bilateral bone marrow biopsy from the posterior iliac crest, bipedal lymphography, abdominal CT scan, skeletal, thoracic and gastrointestinal X-rays, spinal puncture, ORL and clinical examination. The peripheral immunologic state was particularly interesting: there was a substantial decrease in total circulating B-lymphocytes at diagnosis (4.4% = 80/mmc; nv 13 +/- 4% = 287 +/- 130/mmc) and a further decrease after 2 and 4 months of therapy (0.16% = 2/mmc). Three months after completion of therapy, the B-lymphocyte level returned to the base level at diagnosis (7% = 88/mmc). At 10 months after diagnosis and 3 months after completion of chemotherapy, the patient is alive and in good health except for the after-effects of a left hemiparesis. The etiologic and possible pathogenic factors are considered.

[Lymphocytic subpopulations in malignant ascites of ovarian origin. Flow cytometric analysis]. / Sottopopolazioni linfocitarie nell'ascite neoplastica di origine ovarica. Analisi in citometria di flusso.

A flow-cytometric analysis of ascitic fluid (AF) and peripheral blood lymphocyte subpopulations (LS) was performed on 16 patients with ovarian malignancy (OM) and 5 with metastatic peritoneal carcinomatosis (MPC). AF lymphocytes are 58% of total leukocytes in OM patients, 37% in MPC patients, while blood lymphocytes are 14% and 17%, respectively. AF absolute lymphocyte count (total and individual LS) is higher in OM patients. OM patients AF lymphocytes are: T = 70%, CD4+ = -37%, CD8+ = 32% (CD4/CD8 = 1.39), B = 5%, NK cells = 4-10%, CD25+ = 20%, CD69+ = 15%, CD71+ = 3%. In MPC patients the values are generally similar, though CD4+ cells are +7%, CD8+ cells = -14% (CD4/CD8 = 3.17), CD69+ cells = -8%. Untreated OM patients have a AF total and percent lymphocyte count higher than treated ones. Among the latter, however, the CD4/CD8 ratio as well as the number of CD4+, inducer, CD25+ and CD71+ cells are higher. In terms of percent values, the most striking differences involve total T and B lymphocytes (81-87% vs 56-62%, and 10% vs 2%, respectively). With the only exception of absolute NK cell count, OM patients show no correlation between AF and peripheral blood LS pattern. These results agree only partially with data from the literature. Pathophysiologic and clinical considerations support the practical usefulness of LS analysis in AF from OM patients.

[Epidemiology of female ano-genital condylomata acuminata. In relation to the presence of specific types of the human papillomavirus]. / Epidemiologia dei condilomi acuminati ano-genitali femminili. In relazione alla presenza di specifici tipi di human papillomavirus.

The presence of 7 human papillomavirus (HPV) types in genital condylomata acuminata (GCA) from 94 otherwise healthy women was detected by in situ hybridization, employing 3 different DNA probe cocktails (6/11, 16/18 and 31/35/51). HPV+ and HPV- GCA did not differ significantly as to the multiplicity and site of lesions, nor the prevalence of younger age, previous pregnancies or abortions, oral contraception, concurrent vaginal infection, aspecific PAP-test abnormalities and cutaneous hypo-anergy. Of note is that 13/18 HPV+ GCA (72.2%) lodged HPV types (16, 18, 31, 35, 51) which are more commonly related to dysplastic and neoplastic lesions of the female genital tract.

Serum and cytosolic levels of CA549 in breast cancer patients.

CA 549 is a new mucinous circulating tumor marker recognized by two monoclonal antibodies (BC4E549 and BC4N154) recently proposed for breast cancer. In this report we compared the levels of CA 549 and CA 15.3, the best known biomarker for breast cancer nowadays, in 68 sieric and 59 cytosolic samples. Serum samples came from 59 breast patients (24 with primary disease = M-, 18 with systemic disease = M+, 17 with no evidence of disease after surgery = NED) and 9 women with benign breast disease = BBD. The cytosols were prepared from primary breast carcinomas according to the method used for hormonal receptors. At first we evaluated the analytical performance of the immunoradiometric assay for CA 549 (Hybri-BREScan, Hybritech) and its applicability to the cytosolic determination. Using a cut-off value of 12 U/mL for CA 549 and 28 U/mL for CA 15.3 serum levels, we obtained the following percentages of positivities: M- = 21%; M+ = 83%; NED = 0%; BBD = 22% for CA 549 and M- = 33%; M+ = 89%; NED = 18%; BBD = 22% for CA 15.3. CA 549 gave information concordant with CA 15.3 in a high percentage of cases both in sera and in cytosols, but the clinical relevance of cytosolic determination remains to be investigated. Since serum CA 549 showed an adequate sensitivity in M+ patients only, it may be proposed in the follow-up to confirm CA 15.3 abnormal values or as an alternative to it.

Serum TAG 72 levels in different human carcinomas.

Since December 1988, we have measured the TAG 72 serum levels in 326 patients with different carcinomas, especially breast, gastrointestinal and ovarian, using a RIA kit. With a cut-off value of 5 U/mL, a specificity of 100% in the controls and an overall sensitivity of 22% in the neoplastic patients was obtained, with the highest positivities in ovarian (63%) and gastric (58%) carcinomas. Therefore, TAG 72 can be associated with other tumor markers for these latter neoplasms.