Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor growth decreases T-cell recognition of self major histocompatibility complex (MHC) class II molecules by inducing changes in splenic macrophage (M phi) phenotype and function. The current investigation shows tumor-induced alterations in autorecognition also are associated with changes in responsiveness to and production of granulocyte-M phi colony-stimulating factor (GM-CSF). In contrast to normal host (NH) M phi, tumor-bearing host (TBH) M phi failed to express higher MHC class II molecule density after exposure to GM-CSF. Autoreactive T cells stimulated by either NH or TBH M phi were suppressed by GM-CSF. Inhibition of prostaglandin E2 (PGE2) synthesis reversed M-CSF-induced suppression of autoreactivity to NH M phi and, to a lesser extent, to TBH M phi. When TBH autoreactive T cells were stimulated by TBH M phi, autoreactivity increased when GM-CSF was added and PGE2 synthesis was inhibited. Although GM-CSF can contribute to tumor-induced suppression, it did not affect the contribution of GM-CSF during autorecognition. Increased GM-CSF production was responsible, at least in part, for the TBH M phi-mediated suppression. Low concentrations of GM-CSF were produced endogenously by tumor isolates, and GM-CSF production was significantly increased when isolates were stimulated with lipopolysaccharide. Autoreactive T cells stimulated solely by TBH M phi produced more GM-CSF than autoreactive T cells stimulated by NH M phi. Cultures supplemented with several concentrations of NH or TBH M phi produced similar amounts of GM-CSF in a dose-dependent manner. Inhibition of PGE2 synthesis by NH and TBH M phi reduced GM-CSF production equally. Collectively, these results suggest that during tumor growth, responsiveness to and production of GM-CSF alters recognition of self MHC class II molecules.
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PMID:Tumor growth changes responsiveness to and production of granulocyte-macrophage colony-stimulating factor during recognition of self MHC class II molecules. 129 76

A case of B cell lymphoma with clinical and histological features of malignant histiocytosis was described. A 57-year-old male was admitted to Shinshu University Hospital because of transverse myelopathy. Five months before admission, he noticed urinary disturbance, which progressed to urinary obstruction. The following month, bilateral muscular weakness appeared in his legs. A few days later he could not stand up, and was admitted to a local hospital. Neurological examination revealed sensory disturbances below the level of Th12 in all modalities, and marked weakness and hyperreflexia in the lower limbs. A spinal tumor was suspected. However, myelography showed no abnormality. The patient's condition worsened and he became bed-ridden in February 1990. He was transferred to Shinshu University Hospital for further evaluation. On admission he was poorly nourished with fever, anemia, hepatomegaly, and bilateral pretibial pitting edema. No lymphadenopathy was observed. Neurological examination showed total sensory loss below the level of Th12, spastic paraplegia, hyperreflexia in the legs, and urinary obstruction. Laboratory findings revealed an elevated erythrocyte sedimentation rate, increased CRP, pancytopenia, and hypoalbuminemia. Serum level of IgG, IgA, IgM, LDH, ALP, GPT and total bilirubin were increased. CSF and MRI imaging of the spinal cord were normal. Proliferation of atypical histiocytes with marked erythrophagocytosis, which is a characteristic pathological feature of malignant histiocytosis, was observed in peripheral blood and aspirated bone marrow. Immunoenzyme staining of bone marrow using monoclonal antibody L-26, which is a B-cell marker, revealed B-cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of B-cell lymphoma with clinical and histological features of malignant histiocytosis]. 130 24

A 27-year-old woman had a subacute onset of back pain, dysesthesia and weakness of both arms. Neurological examination revealed bilateral pyramidal signs, paresthesia of both hands and arms, and hypalgesia below T-4. CSF showed no abnormal findings. T2-weighted MR images revealed linear high signal within the cervical and upper thoracic cord, but no syrinx. The signs and symptoms resolved substantially within three months, with the exception of paroxysmal itching localized to the right forearm. At age 30, she experienced an acute onset of back pain, and dysesthesia of both feet. She developed weakness of both legs and urinary retention two days after the onset. Neurological examination showed bilateral pyramidal signs in the lower extremities, hypalgesia below T-4, hypopallesthesia on both legs, but no abnormalities in the upper extremities. CSF contained 8 white cells/mm3, protein 17 mg/dl and glucose 44 mg/dl. Oligoclonal bands were not detected. T1-weighted, proton density, and T2-weighted MR images revealed a syrinx formation within the spinal cord, extending from the level of T-2 to T-5. There was no evidence of spinal tumor. MRI of the brain revealed multiple areas of high signal intensity on T2-weighted image, consistent with multiple sclerosis. The signs and symptoms resolved substantially within two months. The syrinx within the thoracic cord reduced in size after two months and disappeared after three months. Two months after the second episode of myelopathy, she experienced right optic neuritis, resolving substantially within three weeks. This case was diagnosed as definite multiple sclerosis based on the clinical and radiological findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Serial magnetic resonance imaging of spinal syrinx formation in a case of multiple sclerosis]. 130 34

A 35-year-old woman was admitted to our hospital with a 3 month history of progressive paraparesis and impairment of bowel and bladder function. MRI suggested a malignant glioma at the level of T9 to L1. Laminectomy and subtotal removal of the tumor was performed. The surgical specimen was a glioblastoma multiforme. An aggressive adjuvant therapy was scheduled to prevent rapid local regrowth and leptomeningeal dissemination. Radiotherapy with a total dose of 65Gy was delivered with chemotherapy including ACNU (2mg/kg) and vincristine (0.2mg/kg). Lymphokine-activated killer (LAK) cells were given intrathecally with a total dose of 1.6 x 10(9) LAK cells with 3 x 10(4) units of IL-2. MRI taken 6 months after surgery revealed no residual tumor, and no malignant cell was detected in the patient's CSF. After physiotherapy, she became able to walk with a stick and was discharged. Chemotherapy (ACNU 2mg/kg/8 weeks) had been further continued for 2 years. She did well until 14 months after surgery, when paraparesis recurred and rapidly progressed to completism. MRI revealed a spinal cord swelling with marked edema, suggesting delayed radiation necrosis. Two years after surgery, MRI showed a marked atrophy of the spinal cord, and no residual tumor. But 3 years after surgery, a round tumor at the level of T11 and T12 was revealed on MRI, and she was admitted to our hospital again. A spinal cord amputation was performed, and the tumor was totally removed without worsening her neurological symptoms. Surgical specimen of the tumor was glioblastoma multiforme again.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of spinal cord glioblastoma multiforme]. 131 Aug 3

One of the morphologic hallmarks of human gliomas are inflammatory infiltrates with accumulation of macrophages in the tumor site. The signals leading to the macrophage response are only at the beginning of being understood. Novel chemotactic factors that have recently been characterized as secretory products of glioblastoma cells may attract mononuclear cells from the blood. Within the tumor tissue blood-derived monocytes and macrophages of the brain tissue, the microglial cells, may increase in cell numbers due to tumor-derived growth factors. Both astrocytoma cell lines and cultured astrocytes have been shown recently to produce granulocyte-macrophage (GM)-CSF. We show that in vitro not only astrocytoma but also glioblastoma cell lines secrete GM-CSF when stimulated with TNF-alpha or IL-1. However, there is no evidence for GM-CSF production by glioblastoma cells in vivo: fresh tumor samples lack the mRNA for GM-CSF and the protein is not detectable in the tumor cyst fluids or the cerebrospinal fluids of glioblastoma patients. This contrasts IL-1 and IL-6 that are detectable in the tumor cyst fluids and IL-6 also in the cerebrospinal fluids of the patients. Unlike GM-CSF, transforming growth factor-beta 2 mRNA is expressed in ex vivo tested glioblastoma tissues. Absence of GM-CSF in vivo may be explained by the presence of tumor-derived inhibitory factors, such as transforming growth factor-beta 2 and PGE which suppress GM-CSF production by glioblastoma cells in vitro. The accumulation of macrophages at the tumor site may be due to local elaboration of chemoattractants and/or not yet defined growth factors rather than due to GM-CSF production.
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) production by glioblastoma cells. Despite the presence of inducing signals GM-CSF is not expressed in vivo. 131 29

Cytokines can have both negative and positive effects on cells undergoing carcinogenesis. The promotion and progression phases of carcinogenesis may be affected by autocrine loops involving cytokines with growth factor activities such as IL-1, IL-2, low molecular weight B cell growth factor, TNF, IL-3, GM-CSF, M-CSF and IL-9. Aberrations in cytokine receptors such as the truncated EGF receptor present in v-erB promotes the growth of neoplastic cells. Aberrant signaling mechanisms, as found with spleen focus-forming virus, which mimics the ligand that activates the erythropoietin receptor, can also contribute to proliferation of preneoplastic and neoplastic cells. In contrast, cytokines such as interferons, LIF, TGF-beta, TNF and leukoregulin, with antiproliferative or differentiating activities, are sometimes capable of inhibiting carcinogenesis. Transfection of tumor cells with cytokine genes, such as IL-2, IL-4 and TNF, can cause suppression of in vivo tumor cell growth by mobilizing host immune and inflammatory cell responses. Thus cytokines and their receptors may play a direct role in early stages of tumor cell development and growth.
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PMID:Cytokines as positive and negative regulators of tumor promotion and progression. 132 42

In vitro TNF alpha induces proliferation and expression of predominantly type A TNF-receptors on B-lymphoma cells. In a pilot study we treated 2 patients with refractory B lymphomas with two courses of TNF alpha and consecutive aggressive chemotherapy (high dose Ara-C and mitoxantrone). TNF alpha was applied on days 1-4, chemotherapy on days 2-4 (TNF-AraM). The TNF-AraM therapy was repeated on day 43. Both patients responded to therapy. TNF alpha therapy induced expression of the 75 kD TNF receptor and the interleukin 2 receptor (CD25) and weakly the 55 kD TNF receptor on leukemic B lymphocytes. Interleukin 3, interleukin 6 and GM-CSF were induced and measured in the serum of patients. The mean time of severe granulocytopenia (less than 0.5/nl) was 9 days (range 8-10 days), the mean time of thrombocytopenia (less than 20/nl) was 5 days (range 2-6 days). In 7 patients, who were treated with high dose Ara-C and mitoxantrone (AraM) mean time of granulocytopenia (less than 0.5/nl) was 23 days (range 18-34 days), and of thrombocytopenia (less than 20/nl) was 13.3 (range 3-27 days). We conclude that TNF alpha can activate tumor B cells in vivo and may exhibit also myeloprotective effects when applied before aggressive chemotherapy.
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PMID:TNF alpha therapy activates human B-lymphoma cells in vivo and may protect myelopoiesis. 132 85

A 63-year-old man developed gradually progressive bilateral loss of vision, cerebellar ataxia, and downbeat nystagmus. Visual acuity was 20/400 OD and 20/200 OS, with cecocentral scotomas OU. Fundus examination showed bilateral optic atrophy and a vitreous cellular reaction. MRI of the brain was normal. CSF protein was elevated, with increased IgG levels but no malignant cells. Biopsy of a pulmonary lymph node showed undifferentiated small cell carcinoma. Neoplastic cells were positive for neuron-specific enolase. Serum contained IgG, which reacted with neuronal and glial cytoplasm and processes. IgG reactivity with systemic tissues and the patient's tumor was not different from that observed with control sera. Paraneoplastic optic neuropathy should be considered in patients with unexplained visual loss and malignancy, and our observations suggest a possible immunologic basis for this condition.
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PMID:Optic neuropathy: a rare paraneoplastic syndrome. 132 6

Autocrine production of growth factors is thought to be an essential element in the development of hemopoietic tumors in vivo. Tumor-derived cell lines frequently show this capability in vitro. It is not understood how autonomous growth in vitro is maintained by lymphoid cell lines that are not of tumorigenic origin. We have previously established human B cell clones that proliferate in serum-free media with unlimited potential. However, the cells need a critical density for continuous growth. Culture supernatant conditioned by these cell lines sustained proliferation even in low density cultures. All B cell clones analyzed were found to secrete the cytokines IL-1 alpha, IL-6, TNF-alpha, and TNF-beta whereas no activity of IL-2, IL-4, low m. w.-B cell growth factor, CSF, or IFN-gamma was recorded. In low density cultures supplemented with rIL-1 alpha, +/- IL-6, +/- TNF-alpha, and +/- TNF-beta together, B cell proliferation is maintained to the same extent as with conditioned medium. Addition of anti-sense oligonucleotides directed to the mRNA of IL-1 alpha, IL-6, and TNF-alpha, respectively, resulted in growth arrest and cell death. This effect could be prevented by supplementation with these cytokines. Scatchard plot analyses and internalization studies revealed that the cells express on their surface high affinity receptors for IL-1 alpha, IL-6, and TNF, respectively, and internalize the cytokines from the supernatant. These results demonstrate that (i) autonomous growth of immortalized B cells is maintained by secretion and reinternalization of IL-1 alpha, IL-6, TNF-alpha, and TNF-beta, (ii) these cytokines act in a synergistic fashion, and (iii) autocrine growth stimulation of human B cells in vitro does not necessarily represent their tumorigenic potential in vivo.
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PMID:Four cell-secreted cytokines act synergistically to maintain long term proliferation of human B cell lines in vitro. 132 86

Recent investigations indicate that malignant melanoma cells can produce distinct cytokines. While differences in the production of single cytokines have been observed among different melanoma cell lines, the extent of variability in the production of single and multiple cytokines between individual melanoma cell lines has not been as thoroughly investigated. A heterogeneity in melanoma cell cytokine production could have important implications for the biology of this aggressive neoplasm since certain cytokines may act as autocrine growth factors or be potent modulators of host immune response to the developing tumor. The purpose of this study is to assess the cytokine production profile of two widely available human melanoma cell lines, A375 and G361. The A375 cell line constitutively expressed the mRNA for IL-1 alpha, IL-1 beta and PDGF-A, with increased expression of these cytokines after induction with PMA. GM-CSF mRNA was expressed by the A375 melanoma line only after induction with PMA. No IL-6 mRNA was detected in the A375 melanoma cell line. The cell culture supernatants from the A375 cells likewise contained a parallel increase in IL-1 activity as determined in the D10 bioassay and secreted GM-CSF and PDGF-AA as measured by ELISA. In contrast, the G361 cell line did not express IL-1, GM-CSF or PDGF-A mRNA (constitutively or after PMA induction) but expressed only IL-6 mRNA and secreted IL-6 activity after PMA induction. These results demonstrate a significant heterogeneity in the production of IL-1 alpha, IL-1 beta, IL-6, GM-CSF, and PDGF in two distinct melanoma cell lines. This study demonstrates that individual melanoma cell lines express and secrete multiple cytokines both constitutively and after stimulation with PMA. The immunodulating and mitogenic properties of these melanoma-derived cytokines may have implications in determining the biologic behavior of different malignant melanomas.
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PMID:Heterogeneity of cytokine production by human malignant melanoma cells. 134 59


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