Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the term thymic hyperplasia is used most commonly to indicate the occurrence of germinal centers in the thymus, cognizance must be taken of the fact that such centers may occur in apparently normal thymuses in both children and adults. A concept of thymic compartmentalization is proposed with origin of germinal centers in the perivascular space (extraparenchymal compartment) of the thymus. These germinal centers contain a high percentage of B lymphocytes in contrast to the true thymic parenchyma. Although the significance of germinal centers in the thymus parenchyma. Although the significance of germinal centers in the thymus in myasthenia gravis remains controversial, removal of nonneoplastic thymus in this condition is of proven therapeutic value. A variety of neoplasms originating in the thymus have previously been lumped together under the single term "thymoma." It is apparent, however, that thymoma, thymic carcinoid, various lymphomas, and germ cell tumors that arise in the thymus differ not only pathologically but also in their clinical behavior. Thymoma is regarded as an epithelial neoplasm and ultrastucturally is characterized by many desmosomes and tonofilaments. The lymphocytes do not behave in a malignant manner, and lymphomas of the thymus should be sharply separated from true thymoma. Poorly differentiated thymic carcinoma and histiocytic lymphoma may be distinguishable only by the electron microscopic demonstration of desmosomes and filaments in the thymic carcinoma. The evidence that Hodgkin's disease of the thymus ("granulomatous thymoma") is not a variant of thymoma appears overwhelming. Lymphoblastic lymphoma of the thymus is a distinctive neoplasm that is especially prevalent in teenage males. High levels of terminal transferase characterize the lymphoblasts and there is a striking tendency for leukemia to occur. Thymic carcinoid is usually nonfunctional, although one-third of the reported cases are associated with Cushing's syndrome. On light microscopy a ribbon pattern and punctate necroses are characteristic of thymic carcinoids. Electron microscopic demonstration of many dense core granules is invaluable in establishing this diagnosis. An important clue to the diagnosis of thymic seminoma (a neoplasm that shows the same radiosensitivity as its testicular counterpart) is the frequent presence of epithelioid and giant cell granulomas and germinal centers. Separation of the various thymic neoplasms described not only is justifiable on pathologic grounds but is often essential for appropriate patient investigation and treatment.
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PMID:Thymic hyperplasia and neoplasia: a review of current concepts. 36 41

In comparison with other rodents, the mastomys is unique as regards the patterns of neoplastic and non-neoplastic diseases that it develops, some of which may constitute suitable animal models for corresponding diseases of man. Among the spontaneous diseases commonly encountered in necropsies of 600 mastomys maintained in a closed colony were: (1) degenerative joint disease of diarthroses and interventricular disks, which develops regularly in the second year of life; (2) renal disease, a type of immune-complex glomerulonephritis, affecting approximately 80% of mastomys in the age bracket 18-36 months; (3) thymomas and thymic hyperplasia affecting 30% of mastomys by the time they are 2 years old or older; (4) a combination of thymoma and polymyositis in a mastomys showing serum-globulin reactivity, presumably auto-antibody against striated muscle; (5) beginning before the age of 1 year, replacement of the normal cell population of the lymphoid tissues by plasma cells, and intense plasma cell infiltration at many other organ and tissue sites; (6) haematopoietic neoplasms, without leukaemic blood, in 10% of mastomys; and (7) histamine-producing argyrophilic carcinoid tumours of the glandular stomach in approximately 60% of old male and 30% of old female mastomys. Additionally, other neoplasms not infrequently encountered in mastomys rarely occur in other rodent species; conversely some neoplasms commonly found in other rodents, including especially tumours of the lung and mammary gland and leukaemia, are rare or absent in mastomys.
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PMID:Spontaneous diseases in a closed colony of Praomys (Mastomys) natalensis. 108 20

Interferons are currently the most widely used biological response modifiers. They are of high clinical value in haematological malignancies (chronic myelogenous leukaemia, multiple myeloma, non-Hodgkin lymphoma), in solid tumours (malignant melanoma, hypernephroma, pancreas neoplasms, carcinoid tumours, Kaposi's sarcoma, glioma, in ovarium, cervix and bladder carcinoma, and in basalioma) and in infectious diseases (chronic hepatitis B, chronic non-A/non-B hepatitis, chronic delta hepatitis, AIDS, Papova virus and Rhinovirus infections, leishmaniasis, leprosy) and some other conditions. Although the mechanism of action of interferons has not been explained in every detail these agents are promising therapeutic means in a number of diseases.
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PMID:Role of interferon in clinical practice. 172 32

Biological modification in cancer therapy involves many different strategies and substances. Bacterial products with established usefulness include BCG, C. parvum and L-Asparaginase. Immunotherapy with such agents has not, however, found general application, although revived interest in 'Coley's mixed toxins' (used earlier this century) paralleled the development of their presumed effector molecules, tumour necrosis factor and lymphotoxin. Many other Cytokines, both natural or recombinant, are now produced on a vast scale following the recent biotechnology revolution. Of these, Alpha Interferons have already proved useful in hairy cell leukaemia, carcinoid tumours, renal cell cancer, Kaposi's sarcoma, chronic granulocytic leukaemia and certain lymphomas, whilst their use as adjuvants or in combination is currently being investigated. More recently, Interleukin-2, which stimulates the clonal expansion of activated T-cells, has shown promise both as a single agent, and when used with lymphokine activated killer (LAK) cells or tumour infiltrating lymphocytes (TILS). A different approach involves the Colony Stimulating Factors such as G-CSF and GM-CSF which reduce the degree and duration of treatment-related myelosuppression, thereby allowing more intensive cytotoxic or radiation therapy, as well as facilitating early recovery following bone marrow transplantation. Monoclonal antibodies have not proved as specific for malignant cells as was originally hoped, but certain tumours, such as lymphoma, are now realistic targets for therapy. Increasingly sophisticated effector mechanisms (e.g. conjugated pro-drugs) and genetically engineered "humanised" monoclonal antibody hybrids present the brightest hopes for the future. Biotherapy, the "fourth modality of cancer treatment" has already assumed its place alongside surgery, radiotherapy and cytotoxic chemotherapy, and will grow in importance as our understanding of the molecular biology of cancer increases in the coming decades.
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PMID:Biological modifiers and their role in cancer therapy. 218 42

During routine screening for anti-nuclear antibodies, using rat liver tissue as substrate, a reactivity against bile duct epithelium was observed in sera from carcinoid tumour patients given human leucocyte-derived IFN-alpha (HuLe IFN-alpha). In a retrospective study, initiated by this observation, the development of serum antibodies to bile duct epithelium was observed in nine out of 12 patients with carcinoid tumours and in three out of 14 patients with hairy-cell leukaemia during their treatment with HuLe IFN-alpha. However, no bile duct reactivity was observed in sera from carcinoid or hairy-cell leukaemia in patients given recombinant IFN-alpha. When analysing the reactivity of positive sera against a panel of rat and human tissues, a uniform reactivity was observed against simple epithelial cells lining the gastrointestinal tract, pancreatic secretory ducts, fallopian tube, kidney tubuli, mesothelium and also against carcinoid tumour cells. The mechanisms promoting autoreactivity against this simple epithelial cell autoantigen is so far unknown. The cytoplasmic as well as the restricted staining pattern of simple epithelial cells may indicate autoreactivity against certain cytoskeletal intermediate filaments, such as cytokeratin 19, 18 and 8, known to be exclusively present in simple epithelial cells and tumours derived from them.
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PMID:Autoantibodies to epithelial cells in patients on long-term therapy with leucocyte-derived interferon-alpha (IFN-alpha). 219 98

In the past decade, interferon, the first of a new class of biologic response modifiers, has undergone extensive Phase I and II clinical evaluation in a broad spectrum of cancers, including hematologic malignancies, lymphomas, and solid tumors. Interferon has been found to have important clinical activity in hairy-cell leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma, chronic myelogenous leukemia, previously untreated multiple myeloma, acquired immunodeficiency syndrome-related Kaposi's sarcoma, malignant carcinoid tumors, intravesically treated superficial bladder cancer, intraperitoneally treated ovarian carcinoma, renal cell carcinoma, and malignant melanoma. Recombinant DNA technology has produced molecules such as the interferons, which are antigenic and can induce antibody formation as part of a generalized immune response. The frequency of antibody occurrence, the magnitude of the antibody response, and the type of antibody induced by the interferons is thought to be related to several factors. These include the specific type of neoplasm for which interferon was administered; the specie of interferon administered; the dose, route, schedule, and duration of interferon administered; and the assay method and sampling time used to determine the antibody titer. Opinions and clinical observations about how these antibodies affect the clinical course of a disease vary among investigators. Some studies have demonstrated that antibody formation is associated with an abrogation of the clinical response, while others have not found any effects on the clinical course of a disease due to antibody presence.
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PMID:Biotherapy with interferon--1988. 246 49

The interferons are the first of a new class of biologic response modifiers that include, among others, the interleukins, colony-stimulating factors, erythropoietin, additional growth factors, and monoclonal antibodies. Interferons have exhibited important clinical activity in hematologic malignancies, lymphomas, and solid tumors. Specific diseases responding to interferons include hairy-cell leukemia (HCL), chronic myelogenous leukemia (CML), low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, multiple myeloma, superficial bladder carcinoma, malignant carcinoid, acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma, ovarian carcinoma, renal cell carcinoma, and malignant melanoma. The potentially antigenic nature of the recombinant interferons can result in the formation of antibodies. These antibodies have been associated with the abrogation of some of the clinical responsiveness of some patients treated with interferons. It is hoped that the controversy existing over the role of antibody formation in treatment efficacy can be resolved by prospective trials using standardized methodology in such areas as assay type, sampling time, route of drug administration, treatment schedule, cumulative dose, and duration of treatment.
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PMID:Biotherapy in clinical practice. 247 4

Two human small cell lung carcinoma cell lines, NCI-H69 and NCI-H128, were used as alternating sources of immunogen to generate monoclonal antibodies to small cell lung carcinoma-associated antigens. BALB/c mice were sensitized with seven injections of live tumor cells, four with NCI-H69 cells and three with NCI-H128 cells. Somatic cell hybridization was performed by fusion of the immune murine splenocytes using syngeneic myeloma cells from the SP2/0 Ag14 cell line. Hybridoma colonies were screened against small cell lung carcinoma cells and normal lung fibroblasts with an enzyme-linked immunosorbent assay. Compared to animals immunized with only NCI-H69 or NCI-H128 cells, alternate immunization resulted in the generation of a significantly higher number of hybridomas that reacted selectively with both tumor cell lines. Monoclonal antibodies from two reactive hybrid clones generated by alternate immunization, SCLC 2051 and SCLC 5023, were uniformly negative to normal human tissues including lung, kidney, liver, spleen, breast, thyroid, brain, small intestine, and colon. While both monoclonal antibodies were nonreactive to paraffin-embedded, formalin-fixed, nonmalignant lung biopsies, the monoclonal antibody SCLC 5023 reacted with tumor cell infiltrates in biopsies from small cell lung carcinoma patients (14 of 14 cases positive), using the immunoperoxidase technique. This monoclonal reagent also reacted with other lung tumor cell types, including atypical carcinoid (5 of 5 positive), epidermoid (4 of 6 positive), undifferentiated and bronchoalveolar (3 of 4 cases each positive) carcinomas. By contrast, monoclonal antibody SCLC 2051 apparently identified an antigen expressed preferentially on small cell lung carcinoma cells (12 of 14 positive) and only rarely reacted with other lung tumor cell types (2 of 34 positive). Both monoclonal antibodies were negative to colon carcinoma, epidermoid carcinoma of the floor of the mouth, breast adenocarcinoma, and B- and T-cell leukemia and lymphoma cells, as determined by the enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoperoxidase techniques. These observations suggest that SCLC 2051 and SCLC 5023 may be of value in identifying tumor-associated antigens expressed in small cell and other lung carcinomas. In addition, the generation of antibody-producing cells towards common tumor-associated antigens may be enhanced by immunization with multiple tumor cell lines of the same histological type.
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PMID:Characterization of two human small cell lung carcinoma-reactive monoclonal antibodies generated by a novel immunization approach. 620 11

Thirteen tumor-derived cell lines of human and nonhuman origin and from various tissues were examined for the presence and density of sigma-1 and sigma-2 receptors. Sigma-1 receptors of a crude membrane fraction were labeled using [3H](+)-pentazocine, and sigma-2 receptors were labeled with [3H]1,3-di-o-tolylguanidine ([3H]DTG); in the presence or absence of dextrallorphan. [3H](+)-Pentazocine-binding sites were heterogeneous. In rodent cell lines (e.g., C6 glioma, N1E-115 neuroblastoma, and NG108-15 neuroblastoma x glioma hybrid), human T47D breast ductal carcinoma, human NCI-H727 lung carcinoid, and human A375 melanoma, [3H](+)-pentazocine bound to high- and low-affinity sites with Kd1 = 0.67-7.0 nM, Bmax1 = 25.5-108 fmol/mg protein, Kd2 = 127-600 nM, and Bmax2 = 942-5431 fmol/mg protein. However, [3H](+)-pentazocine bound to a single site in other cell lines. In human U-138MG glioblastoma, SK-N-SH neuroblastoma, and LNCaP.FGC prostate, Kd = 28-61 nM and Bmax = 975-1196 fmol/mg protein, whereas in ThP-1 leukemia Kd = 146 nM and Bmax = 1411 fmol/mg protein. The sigma-1-like nature of [3H](+)-pentazocine-binding sites was confirmed by competition studies which revealed high affinity for haloperidol and enantioselectivity for (+)-pentazocine over (-)-pentazocine. Interestingly, human MCF-7 breast adenocarcinoma showed little or no specific binding of [3H](+)-pentazocine, suggesting the absence of sigma-1 receptors in this cell line. All cell lines examined expressed a high density of sigma-2 receptors with Kd values for [3H]DTG ranging from 20 to 101 nM and Bmax values of 491 to 7324 fmol/mg protein. Competition studies indicated possible heterogeneity of sigma-2 receptors. While sites labeled by [3H]DTG in all cell lines tested exhibited affinity for haloperidol and preference for (-)-pentazocine over the (+)-enantiomer, human cell lines generally showed 4- to 7-fold lower affinity for haloperidol and approximately 10-fold lower affinity for (-)-pentazocine compared with the rodent cell lines. The high density of sigma-1 and sigma 2-binding sites in these cell lines suggests important cellular functions in cancer, as well as potential diagnostic utility for tumor-imaging agents which target sigma sites. These cell lines may be useful as model systems in which to study the functions of sigma sites in normal tissues, as well as their possible role in tumor biology.
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PMID:Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. 781 73

This study demonstrates the appearance of small bowel tumors on MR images. Sixteen patients with tumors involving small bowel were studied by MRI. All tumors were proven with histopathology. Eleven patients had primary tumors of the small bowel, which included the following: four carcinoid tumors, three adenocarcinomas, two lymphomas, one leiomyosarcoma, and one leiomyoma. Five patients had recurrent or metastatic disease to small bowel: two patients had colon cancer, one patient had pancreatic cancer, one patient had uterine leiomyosarcoma, and one patient had chloroma (leukemia). MR examination included breath-hold T1-weighted spoiled gradient echo (all patients), immediate postgadolinium-spoiled gradient echo (10 patients), and 2 to 4 minutes postgadolinium T1-weighted, fat-suppressed images (all patients). Tumor size, local extent, signal intensity, and enhancement features of tumor and adjacent tissue were determined. Tumor ranged in diameter from 1 to 9 cm (mean, 4.0 cm). Tumors had similar signal intensity to normal small bowel on precontrast images. Fourteen malignant tumors showed heterogeneous enhancement greater than adjacent bowel on gadolinium-enhanced images. Tumor local extent was best shown on precontrast-spoiled gradient-echo images and postgadolinium T1-weighted fat-suppressed images. Image quality was most consistent on breath-hold images. The results of this study show that small bowel tumors are demonstrable on MR images. Precontrast breath-hold T1-weighted spoiled gradient-echo images and gadolinium-enhanced fat suppressed images demonstrate tumor extent most reliably.
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PMID:Small bowel neoplastic disease: demonstration by MRI. 895 28


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