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S C Formenti

Publications and source records attributed to S C Formenti.

26 records · Page 2Linked to original sources
PubMed1989

Primary central nervous system lymphoma in AIDS. Results of radiation therapy.

Primary central nervous system (CNS) lymphoma is one of the clinical presentations of the acquired immune deficiency syndrome (AIDS). Ten patients had biopsy-proven high-grade lymphomas that were confirmed by further staging as limited to the CNS. All ten patients received cranial irradiation (total dose, 2200 to 5000 cGy). Six patients demonstrated complete response (CR) of the intracranial masses at the time of repeat computed tomography (CT) scan, whereas one attained a partial response (PR). Two of the CR patients died of multiple opportunistic infections, two experienced relapse of lymphoma, and died at 7 and 16 months from diagnosis, and two were alive without evidence of disease at 8 and 14 months from diagnosis. The median survival of the whole group was 5.5 months (range, 2 to 16 months). Patients with AIDS-related primary CNS lymphoma may respond to radiation treatment; however, response duration is usually short, and survival is influenced by refractory disease or systemic opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Peripheral T-cell lymphoma.

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.

Adolescent↗
PubMed1989

Human monoclonal antibodies reactive with colon carcinoma: identification by a novel screening procedure with xenografts.

To identify tumor-associated antigens immunogenic to man, human monoclonal antibodies (MAbs) were generated by fusing regional lymph node lymphocytes (LNLs) of each of three colon adenocarcinoma patients with the M5 mouse myeloma cell line. Heterohybridomas in 19 wells secreted human immunoglobulin (Ig) for at least 60 days. To identify immunoreactive MAbs, we devised an immunohistochemical assay with xenografts of six colon tumors. Binding was visualized with a biotin-conjugated goat antihuman Ig antibody followed by an avidin-biotin-peroxidase complex. This assay detected binding with a sensitivity of 0.5 microgram/ml human Ig. Reactivity against tumor-associated antigens (TAAs) in frozen sections of the colon xenografts was detected in 14 of the 19 supernates. However, only nine (three IgGs, five IgMs and one IgA) were reactive against formalin-fixed sections, showing that formalin-fixation destroyed some but not all antigenicity. Four MAbs were cloned and tested against the entire panel of 19 xenografts. One IgM MAb reacted only against colon carcinomas, while the other three (one each of IgA, IgG and IgM) had broader reactivities. Three of the four human MAbs did not cross-react with melanomas. In summary, human regional lymph nodes contain a high proportion of B lymphocytes sensitized to the autochthonous tumor. Immunostaining of human colon tumor xenografts can readily identify human MAbs reactive with colon carcinomas.

Animals↗
PubMed1989

Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon.

To identify tumor-associated antigens that may be immunogenic to man, human monoclonal antibodies (human mAb) were generated by fusing nonsecreting mouse myeloma cells with lymphocytes from regional mesenteric nodes of patients with adenocarcinomas of the colon. One IgG1 human mAb, designated as 14-31-10, was identified by its reactivity against human tumor xenografts. We have studied the reactivity of mAb 14-31-10 with formalin-fixed, paraffin-embedded specimens of human colon. A total of 86 cases were studied, including normal adult and fetal colons, adenocarcinomas of the colon, and a variety of colonic inflammatory diseases and preneoplastic lesions. Intense reactivity was found in 15 of 18 adenocarcinomas of the colon, but not in 10 specimens of normal adult or 4 specimens of fetal colonic mucosa. Interestingly, in four cases of carcinoma, reactivity was also observed in histologically normal mucosa situated 10 cm or more from the primary lesion. On the other hand, no staining was detected in any of the 16 inflammatory lesions. Of the 38 preneoplastic lesions, only 6 showed staining by the mAb: 1 of 5 benign tubular adenomatous polyps, 3 of 9 villous adenomas and tubovillous polyps, 1 of 5 specimens of ulcerative colitis and 1 of 19 specimens of familial polyposis. However, the intensity of staining was only moderate in those cases. Our data, therefore, suggest that the epitope identified by the human mAb 14-31-10 shows preferential expression in preneoplastic and neoplastic lesions of the colon, and in ostensibly normal mucosa at some distance from a primary colonic carcinoma. In all instances, the staining was cytoplasmic, suggesting a cytoplasmic or internal membrane location of the target antigen. This antigen appeared to be distinct from carcinoembryonic antigen, since staining by 14-31-10 was consistently different from that of a mouse monoclonal antibody to carcinoembryonic antigen in serial sections of the same specimens. The restricted reactivity of 14-31-10 suggests its potential application in immunohistochemistry. Moreover, the epitope identified by mAb 14-31-10 may be expressed during the progression of normal mucosa to neoplasia.

Animals↗
PubMed1989

Immunophenotypic analysis of peripheral blood leukocytes at different stages of HIV infection. An analysis of asymptomatic, ARC, and AIDS populations.

Blood leukocytes from 51 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related syndrome (ARC) were immunophenotyped with the use of monoclonal antibodies and flow cytometry. The patients were placed into four clinically defined groups: HIV-positive asymptomatic (HIV+/A, 8); persistent generalized adenopathy (14); Kaposi's sarcoma (12); and opportunistic infections (17). Immunophenotypes were compared between groups. Statistically significant differences were seen in absolute lymphocyte counts, total T-cells, helper/inducer T-cells, the helper inducer subset of CD4+ lymphocytes, the suppressor inducer subset of CD4+ lymphocytes, activated helper T-cells, and natural killer cells. CD8+ cells and subsets were not statistically different between groups, possibly obscured by large ranges, but median values suggested differences. Results indicate a pattern of increasing or decreasing numbers of certain subpopulations as HIV infection progresses.

AIDS-Related Complex↗
PubMed1988

Peripheral blood mononuclear cell abnormalities and their relationship to clinical course in homosexual men with HIV infection.

Quantitative abnormalities of leukocyte subpopulations have been shown to correlate with clinical status in human immunodeficiency virus (HIV) infection. We have performed peripheral blood leukocyte phenotyping in 23 HIV-seropositive homosexual men, and correlated the results with clinical follow-up information. Individuals with CD4+ greater than 400/mm3 (Group 1) had less severe abnormalities in other mononuclear cell subpopulations than patients with CD4+ less than 400/mm3 (Group 2). Group 1 had decreased CD4+CDw29+ (B-cell inducer) cells, compared to HIV-seronegative homosexual controls, with normal CD4+CD45R+ (suppressor-inducer) cells, suggesting that CD4+ subpopulations are reduced at different rates. Group 2 had decreased counts for both CD4+CDw29+ and CD4+CD45R+ cells. Both groups had increased cytotoxic T cells (CD8+CD11b-), with decreased B cells and CD4+/CD8+ ratios, compared to HIV-seronegative homosexual controls. The Group 2 patients with subsequent clinical deterioration had particularly low CD4+ cells, CD4+CD45R+ cells, CD2+Ta1+ cells, and CD4+/CD8+ ratios and high CD8+CD11b- cells, compared to those with clinically stable illness. Our findings suggest that specific leukocyte subpopulations are altered differentially at various stages of HIV infection. However, the study involved only quantitative measurements of specific T- and B-cell subsets with no attempt to measure in vitro function. It is of course possible that normal numbers of cells in these subpopulations might be functionally deficient.

Antigens, Differentiation↗
PubMed1986

Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results.

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.

Acquired Immunodeficiency Syndrome↗