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Biomedical subjects

E Hu

Publications and source records attributed to E Hu.

At least 55 records · Page 3Linked to original sources

Immunogenetic analysis of bone marrow aspirates in patients with non-Hodgkin lymphomas.

The immunogenetic analysis (IGA) on the staging bone marrow aspirates in 15 patients with non-Hodgkin lymphoma (NHL) is reported. We found the sensitivity of IGA and morphologic examination in detecting bone marrow involvement by malignant lymphoma to be 91% and 82%, respectively. In 11 cases there was agreement between the morphologic findings and IGA. In 8 of these 11 cases, IGA confirmed the morphologic involvement of the bone marrow by demonstrating clonal rearrangement of either the immunoglobulin heavy- and/or light-chain or the T-cell receptor beta chain (TCR) genes. In 3 of these 11 cases, morphology showed no involvement and IGA showed germline configurations for both the immunoglobulin heavy- and light-chain or the TCR genes. In 2 additional cases the techniques proved to be complementary, as involvement was detected by only 1 of the 2 procedures. In 1 of these 2 cases, IGA showed gene rearrangement while morphologic examination was negative for involvement by NHL, while in the other case, morphologic examination showed involvement by NHL, but IGA did not show gene rearrangement. IGA was also useful in determining the clonality of solitary lymphoid nodules in the 2 remaining cases when morphologic interpretation was equivocal. In the 12 cases with bone marrow involvement, the immunophenotype and immunogenotype agreed in 11 cases. In the one case in which there was a discordance between the immunophenotype and immunogenotype, the immunophenotype was incorrectly interpreted as B-cell lineage, while the immunogenotype demonstrated a T-cell lineage. IGA also demonstrated a clonal population in 1 case of T-chronic lymphocytic leukemia where other techniques could not demonstrate the clonality of the pathologic process. IGA analysis may detect bone marrow involvement in NHL which may not be detected by morphologic examination because of patchy distribution.

B-Lymphocytes↗

Phase I toxicity and pharmacology study of trimethylcolchicinic acid in patients with advanced malignancies.

A phase I study of trimethylcolchicinic acid (TMCA) given orally once daily for 5 days every 3rd week was performed in 19 patients with advanced malignancies. Myelosuppression and mucositis were the major toxicities observed. Serum TMCA levels were monitored and appear to be useful in predicting toxicities. A partial response was seen in one lymphoma patient and stabilization of disease was noted in one patient each with prostatic and ovarian cancer.

Administration, Oral↗

Detection of specific t(14;18) chromosomal translocations in fixed tissues.

The present study was undertaken to establish the incidence of t(14;18) (q32:q21) chromosomal translocations detectable by a polymerase chain reaction (PCR) assay on fixed lymphoma biopsies. DNA samples from 113 formalin-fixed, paraffin-embedded tissue biopsies (non-Hodgkin's lymphomas, 96 cases; Hodgkin's disease, six cases; reactive, 11 cases) were amplified by the PCR. Of the 96 non-Hodgkin's lymphoma cases, 56 had a follicular pattern and 40 had a diffuse pattern. Polymerase chain reaction-amplifiable t(14;18) chromosomal translocations were detected in 23 of 43 follicular low-grade lymphomas, one of eight follicular intermediate grade lymphomas, one of five follicular high-grade lymphomas, and one of 10 diffuse large-cell lymphomas. The remaining 30 diffuse lymphomas represented the spectrum of the Working Formulation classification. There were six biopsy specimens of Hodgkin's disease and 11 biopsy specimens of follicular hyperplasia; all were negative. The translocation was not detected in 16 biopsies (non-Hodgkin's lymphomas, seven cases; follicular hyperplasia, nine cases) from patients infected with the human immunodeficiency virus. Since this procedure uses the widely available fixed paraffin-embedded material, correlative studies between histology and genetic aberrations can be readily undertaken.

Chromosomes, Human, Pair 14↗

Active-specific immunotherapy for melanoma.

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.

Adjuvants, Immunologic↗

Hemolytic anemia in a cancer patient treated with recombinant interferon-gamma.

Currently, three classes of interferon are used in the treatment of malignancies. Interferon-gamma is the best studied. Bone marrow suppression as well as immune hemolytic anemia have been described. Heretofore, only bone marrow suppression has been attributed to interferon-gamma (IFN gamma). In this report, we describe a woman with lung cancer being treated with IFN gamma in whom acute hemolytic anemia occurred. Immune hemolysis did not appear to be the cause. We concluded that in addition to bone marrow suppression, hemolysis should be considered in a patient receiving IFN gamma in whom an unexplained drop in hematocrit occurs.

Adenocarcinoma↗

Phase I study of combination recombinant interleukin-2 and interferon gamma in patients with advanced malignancies.

A phase I trial of interleukin-2 and interferon gamma combination treatment in patients with advanced malignancies was performed based on preclinical in vitro and in vivo data which demonstrated synergistic antitumor effect. The toxicities, immune parameters, and tumor responses are described. The clinical and biologic maximal tolerated doses were extrapolated from these data.

Adolescent↗

Detection of occult CNS involvement of follicular small cleaved lymphoma by the polymerase chain reaction.

A patient with follicular small cleaved lymphoma presented with an unusual clinical relapse in the central nervous system (CNS) without morphologic evidence of lymphoma cells in the cerebral spinal fluid (CSF). Molecular genetic analysis of the small number of cells in the CSF after in vitro DNA amplification by the polymerase chain reaction demonstrated the presence of an abnormal translocation sequence between chromosomes 14 and 18. A similar translocation could be detected from the original fixed archival lymph node biopsy and from a small proportion of circulating mononuclear cells. These results indicated that occult lymphoma cells were present in the CSF and peripheral blood. Secondary CNS lymphoma involvement was identified at autopsy. This case demonstrates the enhanced sensitivity of lymphoma diagnosis from poorly cellular specimens after in vitro DNA amplification.

Aged↗

Synergistic antitumor effects of interleukin 2 and the monoclonal Lym-1 against human Burkitt lymphoma cells in vitro and in vivo.

Interleukin 2 (IL-2) regulates immune responses by inducing proliferation and differentiation of T-cells into cytotoxic cells, inducing lymphokine activated killer activity and enhancing antibody dependent cellular cytotoxicity (ADCC). Lym-1, a monoclonal antibody, recognizes a membrane antigen present on the surface of B-lymphoma cells and can be used for ADCC. We therefore used Raji (human Burkitt lymphoma) cells to study the efficacy of combination therapy with IL-2, lymphokine activated killer activity, and Lym-1. In vitro ADCC assays using Lym-1 showed that preincubation of peripheral blood lymphocytes with IL-2 had a synergistic antitumor effect. The maximum synergism was achieved when peripheral blood lymphocytes were incubated with IL-2 for 3 days as compared to 1 or 2 days, with the optimal concentration of IL-2 being 1000 units/ml. This effect was specific for Lym-1 as demonstrated by experiments using an irrelevant (antimelanoma) monoclonal antibody or an irrelevant target cell (A375). The ADCC was blocked by an anti-Fe receptor antibody (3G8). In vivo experiments performed by growing Raji tumors in nude mice also demonstrated the increase in ADCC and the synergism between IL-2 and Lym-1 in terms of decreased tumor size and growth. The mechanism of this synergy is probably from activation of cells mediating ADCC. This raises the possibility that treatment of patients with low doses of IL-2 in combination with Lym-1 may enhance immune responses and thereby antitumor activity.

Animals↗

Detection of clonal T-cell receptor gene rearrangements in the peripheral blood of patients with mycosis fungoides/Sezary syndrome.

Involvement of the peripheral blood in mycosis fungoides/Sezary syndrome (MF/SS) has a significant impact upon prognosis, but it is often difficult to distinguish circulating cells of MF/SS from atypical reactive lymphocytes. We compared the standard morphologic method of identifying leukemic cells, the Sezary preparation, to a genotypic method using Southern blot analysis of T-cell receptor gene rearrangements in concurrent blood samples. We studied 26 MF/SS patients, five of them in remission, together with five controls from cases of various non-MF/SS skin diseases. Six of 26 MF/SS patients had morphologically atypical circulating leukocytes (3%, 4%, 5%, 14%, 16%, 19%). Seven of 26 MF/SS patients had clonal T-cell receptor gene rearrangements, including the four patients with the greatest percentages of atypical cells and three patients lacking atypical cells. Six of seven patients had skin disease at the time of sampling, including three with erythroderma, two with generalized thick plaques, and one with generalized patches, while one patient was in clinical remission. All five controls lacked morphologic and genotypic evidence of atypical or clonal T-cells. Relative to genotyping, in our series the Sezary preparation was less sensitive and less specific. There were three apparent false negative results in the Sezary preparations, and two potential false positive (patients with 3% and 4% atypical leukocytes); however, there was agreement between the two techniques in most cases. We conclude that gene rearrangement studies may provide an effective test with which to assess the peripheral blood of MF/SS patients.

Blotting, Southern↗

Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center.

The reported experience with Hodgkin's disease (HD) in the United States has come primarily from large referral centers that attract a predominantly white population of high socioeconomic status (SES). The majority of these patients had the nodular sclerosis (NS) histologic subtype and asymptomatic stage I/II disease. We have reviewed the records of 178 patients with HD seen within the past 17 years at Los Angeles County-University of Southern California Medical Center (LAC/USC), which is a nonreferral, government-operated facility. Our patient population was found to be heterogeneous, with 38% white, 22% black, and 36% Hispanic. Systemic "B" symptoms were noted in 62% of patients at diagnosis, and 63% had advanced disease (stage III or IV). NS pathologic subtype was present in only 52% of the group. Comparison between the races revealed: (1) Hispanics had a higher incidence of lymphocyte depleted subtype and less NS than whites (P less than .06); (2) whites had equal distribution between stages I/II and III/IV; (3) blacks and Hispanics presented more frequently with stage III/IV (P = .10); and (4) extranodal involvement occurred most often in bone in whites, and was equally distributed between liver, lung, and bone in blacks and Hispanics. We conclude that the lower SES, mixed racial population seen at our institution more closely resembles the reports of HD in Third-World countries and is characterized by advanced symptomatic disease. Further, the clinical pathologic characteristics of HD in the United States may vary significantly, depending upon the precise ethnic and socioeconomic status of the patients being served.

Adolescent↗

Treatment of B cell malignancies with 131I Lym-1 monoclonal antibodies.

Lym-I is a murine IgG2a monoclonal antibody (MAb) that is B-cell specific but has greater avidity for malignant B cells when compared with normal B lymphocytes. It was originally produced by immunizing mice with nuclei of cultured cells from a patient with Burkitt's lymphoma. Ten patients with progressive refractory B-cell malignancies were treated with 131I-labelled Lym-I. Treatment with 131I Lym-I produced complete or partial remissions in 4 patients. Toxicity did not occur or was mild in most patients. The only significant complications included two instances of fistula secondary to necrotic lymphoma and one instance of hypotension. Human antimouse antibodies occurred in only 2 patients after multiple injections of Lym-I antibody. This experience was in contrast to treatment of B-cell malignancies with unconjugated Lym-I alone. Unconjugated Lym-I also caused no significant toxicity but was less effective than 131I Lym-I.

Antibodies, Monoclonal↗

Non-Hodgkin's lymphoma containing both B and T cell clones.

We describe a patient in whom two lymph node biopsies removed 18 months apart disclosed histologic and immunophenotypic evidence of a non-Hodgkin's lymphoma containing neoplastic lymphocytes of both B and T type. Analyses of immunoglobulin and T cell receptor genes confirmed the presence of separate B and T cell clones. In addition, immunogenotyping revealed the possibility of a second B cell clone within the patient's tumor. Development of a multiclonal lymphoma in this patient may relate to the carcinogenic effects of chemotherapy or to a predisposition for neoplastic transformation of lymphocytes due to a previously diagnosed autoimmune condition. Another possible explanation is that the lymphoma implies the existence in this patient of a transformed lymphocyte-committed stem cell that is capable of generating both B and T lineage clones.

B-Lymphocytes↗

Phase I study of recombinant human interferon beta in patients with advanced cancer.

Twenty-two patients with advanced cancer were entered into a phase I study of recombinant human interferon beta (IFN-beta). The maximum tolerated dose was 100 X 10(6) IU administered intravenously on a three times weekly schedule, and persistent fever was the dose-limiting toxicity. The majority of patients tolerated administration of IFN-beta well with negligible hematologic toxicity. Details of the clinical effects of escalating doses of recombinant human IFN-beta, administered three times weekly, are described.

Chemical and Drug Induced Liver Injury↗

Chemotherapy of malignant thymoma. Case report and review of the literature.

The authors report the case of a patient with malignant thymoma unresponsive to combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] and cisplatin/VP-16) who subsequently achieved clinical response to continuous daily prednisone. A review of the literature indicates that prednisone and cisplatin are the most active agents in the treatment of malignant thymoma.

Antineoplastic Combined Chemotherapy Protocols↗

Immunoglobulin gene rearrangements in Hodgkin's disease.

An initial survey of biopsy specimens from 16 cases of Hodgkin's disease revealed clonal immunoglobulin gene rearrangements in one specimen, which contained large numbers of Reed-Sternberg (R-S) cells. As a result of this finding, the configuration of immunoglobulin and T-cell receptor gene DNA was investigated in biopsy tissues from other cases that were histologically and immunophenotypically consistent with Hodgkin's disease and contained numerous R-S cells. In six of seven such specimens (all of the nodular sclerosing subtype), selected solely on the basis of high R-S cell content and sufficient frozen tissue for study, at least one immunoglobulin gene was found to be rearranged in a clonal manner. Additionally, tissue samples obtained at two different time points from the original patient who showed immunoglobulin gene rearrangements revealed identical patterns of rearrangement. In the majority of cases, only a single gene showed rearrangement, and the rearranged bands in Southern blot autoradiograms were usually considerably less intense than the germline bands. No rearrangements of T-cell receptor DNA were detected in any case with a probe for the beta T-cell receptor gene. The results suggest that clonal cell populations possessing uniform immunoglobulin gene rearrangements are present in tissue in some cases of Hodgkin's disease. It is not possible to determine which cells contain these rearranged genes, but the increased incidence of detectable rearrangements in cases with high numbers of R-S cell raises the possibility that immunoglobulin gene rearrangement occurs in these cells.

Chromosome Aberrations↗

Diagnosis of B cell lymphoma by analysis of immunoglobulin gene rearrangements in biopsy specimens obtained by fine needle aspiration.

Histologic diagnosis of lymphoma is far more difficult in the disaggregated cells obtained by percutaneous aspiration of lymph nodes than in tissue sections prepared from excisional biopsy specimens. However, the simplicity, economy, and safety of aspiration biopsy makes this an attractive diagnostic option in certain situations. In the present study, we demonstrate that lymph node aspirates provide material that is both suitable and sufficient for accurately detecting clonal proliferations of B cells by analysis of immunoglobulin gene rearrangements. The rearrangements detected in aspirated tissue serve as clonal markers that can be directly compared with the rearrangements found in histologically confirmed lymphoma removed by open biopsy. The application of gene rearrangements to aspirated material therefore offers a useful method of diagnosing lymphoma, particularly for the purposes of more thorough staging at initial presentation or the evaluation of tissues for possible relapse.

B-Lymphocytes↗

Detection of B-cell lymphoma in peripheral blood by DNA hybridisation.

As an alternative to morphological identification of circulating neoplastic lymphocytes in the blood of patients with non-Hodgkin's lymphoma, DNA of peripheral blood lymphocytes was analysed for clonal immunoglobulin gene rearrangements in 29 patients with low-grade B-cell lymphomas. 76% of the patients showed clonal rearrangements of immunoglobulin genes in their blood, including 58% of those with no other evidence of disease. In seven patients from whom paired samples were available the rearranged bands found in the blood and in lymph-node biopsy specimens containing histologically confirmed lymphoma were identical. Detection of circulating lymphoma cells by use of tumour-specific anti-idiotype antibodies and cytofluorimetry showed complete agreement with the results of DNA analysis.

B-Lymphocytes↗