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)

We report a primary malignant mixed mesodermal tumor in the right ovary of 75-year-old woman. She was admitted to Kobe West Municipal Hospital because of an abdominal fullness and an upper abdominal pain. A laparotomy yielded yellowish-clear ascites (2,000 ml) a tumor located in the right ovary, an upper abdominal mass the size of a child's head between the stomach and the transverse colon, and disseminating small tumors of the peritoneum. The left ovary and uterus showed no particular change. Four months after the onset of her symptoms, the patient died of carcinomatous cachexia and dyspnea. On microscope examination, the tumor of right ovary showed combined features of an adenocarcinoma, an adenosquamous carcinoma and a serous cystadenocarcinoma with foci of a heterologous stromal differentiation, that is an area of immature, striated muscle cells, bone, and cartilage and undifferentiated spindle cells. Immunohistochemical stains were useful for determining elements of the tumor cells. Epithelial tumor cells were positive for cytokeratin, epithelial membrane antigen, and CEA, while mesenchymal tumor cells were generally positive for vimentin and the immature muscle cells were especially positive for desmin, actin, and myosin. Additionally, myoglobin was identified in the rhabdomyoblast. Finally, S-100 protein was present in cartilage area and partially present in the adenocarcinomatous element.
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PMID:[A malignant mixed mesodermal tumor of the ovary]. 217 88

It has long been known that complex interactions occur between tumors and normal host immune cells. The human melanoma cell line A375 has been used previously as an indicator cell for tumor cell cytotoxicity mediated by monocytes. During other studies on this tumor cell line, we noted that the conditioned media harvested from A375 cultures induced both the human monocytoid cell line U937 and human blood monocytes to release the cytokine tumor necrosis factor (TNF). We characterized this tumor factor which induced TNF release by monocytic cells. Purification was performed using ammonium sulfate precipitation, ion exchange (DEAE) chromatography, gel filtration, and reversed-phase high performance liquid chromatography. The factor copurified with granulocyte-macrophage colony-stimulating factor (GM-CSF). The purified material caused the release of TNF by U937 cells and stimulated formation of granulocyte-macrophage colonies in methyl cellulose. TNF release by U937 cells in response to A375-conditioned medium was inhibited by neutralizing antibodies to GM-CSF. The TNF-inducing activity in A375-conditioned medium was completely removed by an anti-GM-CSF affinity column. Western blotting using antibodies to GM-CSF confirmed a single Mr27,000 band in A375-conditioned medium. We found that recombinant human GM-CSF stimulated TNF production by the same cells as the tumor-conditioned medium. These data show that A375 human melanoma cells produce GM-CSF, which in turn causes TNF production by cells in the monocyte lineage. The combination of GM-CSF production by the tumor and TNF production by immune cells may influence not only tumor growth but also some of the paraneoplastic syndromes associated with malignancy such as hypercalcemia, cachexia and leukocytosis.
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PMID:Stimulation of tumor necrosis factor release from monocytic cells by the A375 human melanoma via granulocyte-macrophage colony-stimulating factor. 218 30

The effect of cachexia on insulin secretion was examined in adult male rats. Isolated islets of Langerhans from Walker 256 tumor-bearing rats secreted less insulin by glucose stimuli as compared with the control group; this was accompanied by significant change in 45Ca2+ outflow rate. Reduced insulin secretion to glucose stimuli in tumor-bearing rats probably led to low insulinemia (one-third). These findings indicate that reduced insulin secretion is probably an important factor for the development of cachexia in Walker 256 tumor-bearing rats.
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PMID:Insulin secretion in Walker 256 tumor cachexia. 219 28

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are soluble factors that play a pivotal role in acute and chronic inflammation. TNF is a 17 Kda protein mainly released by monocytes and macrophages and is a common mediator of toxic shock, cachexia and tumor necrosis. IL-1 was first described as a lymphocyte activating factor and it was then discovered that IL-1 has a number of other biological activities and that there are at least two major types of IL-1 (alpha and beta) which bind to the same receptor. Recently it has been shown that TNF and IL-1 beta have an important role in bone resorption.
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PMID:[Bone resorption and cytokines: the role of IL-1 beta, TNF and lymphotoxin]. 220 96

In addition to the induction of tumor regression, tumor necrosis factor (TNF) has been implicated as the causative agent in a number of pathologies, including cachexia, septic shock, rheumatoid arthritis, autoimmunity, and induction of HIV expression. We propose that this complex physiology might be manifest by different forms of TNF: the 17 kd secretory component, the 26 kd transmembrane form, or both. To determine whether the 26 kd form of TNF was biologically active and whether its biology differed from that of the secretory component, we generated uncleavable and solely secretable mutants of TNF and studied their biological activities. We found that an uncleavable mutant of the 26 kd cell surface transmembrane form of TNF kills tumor cells and virus-infected cells by cell-to-cell contact, and that TNF need not be internalized by its target to kill. Thus, the 26 kd integral transmembrane form of TNF may function in vivo to kill tumor cells and other targets locally in contrast to the systemic bioactivity of the secretory component.
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PMID:A nonsecretable cell surface mutant of tumor necrosis factor (TNF) kills by cell-to-cell contact. 220 85

The rat Leydig cell tumor is a well characterized model of the humoral hypercalcemia of malignancy. The studies reported here were provoked by the observation that tumor-bearing rats become extremely cachectic and develop hypertriglyceridemia as they become hypercalcemic. Since the bone resorbing cytokine tumor necrosis factor (TNF)/cachectin is associated with cachexia and hypertriglyceridemia, we examined hypercalcemic tumor-bearing rats for evidence of increased TNF production using a TNF radioimmunoassay. We found that immunoreactive TNF was increased in the plasma of tumor-bearing rats. The increase in plasma TNF was comparable to that previously shown in hypercalcemic nude mice bearing Chinese hamster ovarian cell tumors transfected with the human TNF gene. There was no detectable TNF activity in tumor culture media which suggested that the tumor itself was not the source of excess TNF production. However, we found that tumor cell conditioned media enhanced the production of TNF activity by normal macrophages in vitro, indicating that increased TNF production in vivo may result from a tumor factor(s) which stimulates TNF production by normal immune cells. When TNF was added together with tumor products to organ cultures of fetal rat long bones, osteoclastic bone resorption was potentiated. These data are consistent with the concept that in this model of the humoral hypercalcemia of malignancy, increased TNF production by normal immune cells is increased, has systemic effects as suggested by cachexia and hypertriglyceridemia, and may work in concert with factors produced directly by tumor cells to overwhelm normal calcium homeostasis.
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PMID:Increased production of tumor necrosis factor by normal immune cells in a model of the humoral hypercalcemia of malignancy. 223 14

The patient, a 39-year-old man, underwent initial surgery for total removal of a left C-P angle tumor histologically diagnosed as epidermoid carcinoma. Postoperative irradiation therapy was administered over the whole brain and spinal cord, 50 Gy and 20 Gy respectively. The patient was then released without symptoms. 15 months later, he was readmitted for paraparesis and urinary retention. CT scan revealed no tumor recurrence in the intracranial area but did show intraspinal cyst of the lower thoracic level. After cyst-subarachnoid shunt, severe acute hydrocephalus was shown on CT scan. His general condition progressively deteriorated. Ten days after the shunt operation, he died of systemic bleeding tendency and cachexia. During surgery, the authors obtained dark yellowish fluid from the intraspinal cyst. Gene survey of the specimen from the cyst wall disclosed abnormality. It is important in the diagnosis of primary intracranial epidermoid carcinoma that we rule out the existence of extracranial cancer and direct invasion through the dura. Though epidermoid carcinoma can be fatal, radiotherapy was an efficacious treatment in the present case, as well as in three other reported cases.
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PMID:[C-P angle epidermoid carcinoma: a case report]. 224 98

We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells.
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PMID:Lipolytic factors associated with murine and human cancer cachexia. 225 Mar 13

We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.
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PMID:Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. 225 57

Interferon alpha (IFN-alpha) has been shown to be effective in treating HIV-associated KS in at least 30% of patients, and Zidovudine has proved beneficial for AIDS patients. Moreover, both drugs have demonstrated an inhibitory effect on HIV replication. Based on the above, we combined IFN-alpha and zidovudine for treatment of HIV-associated KS in order to evaluate tolerance and clinical efficacy. Twenty-one homosexual men with histologically proved HIV-associated KS were treated in an open trial with rIFN-alpha-2a 18 X 10(6) IU every second day and zidovudine 800-1200 mg/d. Treatment was discontinued within the first month in six patients: three of them developed subjective intolerance, and three others contracted severe opportunistic infections or HIV-cachexia. Fifteen evaluable patients received combination treatment over a period of 2-20 months (average 10 months). The dosage was reduced as required based on drug-induced cytotoxicity. Complete remission was observed in four patients, partial remission in three, stable disease in two, and progression in six, resulting in an overall response rate of 46%. Negative p24 expression prior to treatment was a positive predictor. Although extracutaneous involvement had a negative influence on tumor remission, even patients with a mean initial T-helper cell count below 100 mm3 responded positively. In conclusion, combination therapy of rIFN-alpha-2a with AZT may effectively control HIV-related Kaposi's sarcoma in more than 40% of patients. In contrast to monotherapy with IFN-alpha, patients with severely reduced immune systems will also benefit from combined treatment.
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PMID:Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects. 225 33


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