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)

The tumor promoting phorbol esters can affect early embryonic development by causing interference with the normal pathways of cellular growth and differentiation. The present study was designed to: a) define a time in organogenesis when a vertebrate embryo model, the chicken, was sensitive to the phorbol ester 12-0-tetradecanoyl-13-acetate (TPA), and b) attempt a rescue of the embryos disturbed by TPA with simultaneous addition of insulin. In embryos treated at days 2 and 3 of development, TPA caused dose-dependent mortality. Survivors were biochemically retarded as indicated by their decreased weight, protein, DNA, RNA, total creatine kinase, triglycerides, phospholipids and cholesterol contents. When intermediate doses of TPA (50 ng/embryo) were applied together with insulin (100 ng/embryo), the embryonic growth disturbance was largely antagonized. These data, generated with an in vivo whole embryo, These data, generated with an in vivo whole embryo, support the strong link between the mode of action of insulin and signal transduction mechanisms typical of phorbol esters.
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PMID:Insulin reverses the growth retardation effect of phorbol ester in chicken embryos during organogenesis. 266 46

1. Growth and viability of in vitro cultured Ehrlich ascites tumor cells are not significantly impaired by exogenous creatine up to 40mM. Retardation of cell growth by higher concentrations depends on cell density. 2. Ehrlich cells grown in the presence of high concentrations of creatine accumulate creatine phosphate to high levels (up to 23 nmol/10(6) cells in the presence of 40mM creatine). 3. A nearly complete interruption of glycolytic ATP production or inhibition of the oxidative ATP synthesis reduces the maximal creatine to about 40-50% of controls. 4. Studies on the intracellular distribution of creatine kinase have shown, that the enzyme is only associated with the mitochondrial fraction. Titration of isolated mitochondria with digitonin revealed that the activity is located in the inter-membrane space and partly bound to the outer site of the inner membrane. 5. By growth of Ehrlich cells in creatine-free medium it is possible to obtain "creatine phosphate-depleted" cells (creatine phosphate less than 10% of controls). The growth of creatine phosphate-depleted cells as compared to controls is significantly reduced under energetic stress situations. The protein synthesis of these cells after an energetic stress (lack of glucose and oxygen) is significantly reduced as compared to creatine phosphate containing cells. 6. It is concluded that in these cells creatine kinase/creatine phosphate is a thermodynamic buffer system and not part of an energy shuttle as is postulated for muscle cells.
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PMID:Investigations on the function of creatine kinase in Ehrlich ascites tumor cells. 275 96

Human 253J urinary carcinoma cells and the F1 (low-metastatic) and F10 (high-metastatic) variants of the B16 murine melanoma cell line have been shown to activate heparinized human platelets by an adenosine diphosphate (ADP)-dependent mechanism based on inhibition by creatine phosphate/creatine phosphokinase and the identification of aggregating concentrations (1 to 2 mumol/L) of ADP in cell-free culture supernatants by high-performance liquid chromatography. Aggregation did not occur in citrated samples, and hirudin was without effect. Studies were carried out to determine whether extracellular ADP arose from nonspecific cell damage during cell isolation and manipulation or was a specific process under control of the tumor cells themselves. Tumor cell damage during harvesting was shown not to be a factor because the amounts of ADP produced by the three cell lines (a) were inversely related to the appearance of lactic dehydrogenase in the culture supernatants and (b) were similar when measured in confluent monolayers, either in tumor cells after detachment and resuspension or after crossover studies involving culture in, alternatively, Hanks' balanced salt solution and minimal essential medium. Metabolic control of ADP production was indicated by the fact that (a) it was not dependent on cell number, which suggests feedback inhibition; (b) it was reduced 60% when tumor cells were treated with p-chloromercuribenzene sulfonate; and (c) it was completely abolished in those treated with iodoacetic acid, which might be expected to increase nonspecific leakage. These studies indicate that ADP production by these three lines does not arise due to leakage induced by nonspecific membrane damage during cell harvesting and manipulation but is a discrete process under metabolic control of the tumor cells. Moreover, in B16 murine melanoma cells the ability to produce ADP and to support platelet aggregation appears to be unrelated to metastatic potential insofar as identical results were obtained with the F1 and F10 variants.
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PMID:Platelets in tumor metastasis: generation of adenosine diphosphate by tumor cells is specific but unrelated to metastatic potential. 283 29

New treatment approaches in the fight against SCLC are clearly on the horizon and some are already in clinical trials. With this in mind, several comments concerning future directions in staging this disease can be made: 1. Staging is important and complete staging is needed in order to continue to build meaningful information. 2. Limited/Extensive disease categories are in use and remain important; yet this system is not completely adequate. There are subsets within each group that do better: minimal disease versus bulky disease in limited stage, extraabdominal v intraabdominal in extensive disease, and single organ versus multiple organ involvement. Therefore, a new staging system is needed. The TNM system is designed primarily to define surgical resectability and will thus not adequately address the issues for SCLC unless the N and M categories are markedly enlarged. A staging symposium was recently held in Europe to begin to address potential approaches to staging and an American staging conference is planned. 3. Biomarkers: In the broad range of possible markers, most are not sufficiently sensitive or specific to supplant clinical exam and routine testing. But newer tests such as NSE, CK-BB and tumor surface antigen expression and recognition may impact on staging in the near future. 4. Finally, as the biology of SCLC is further understood, much of the derived understanding will likely change the staging and prognostic factors.
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PMID:Staging, prognostic factors, and special considerations in small cell lung cancer. 283 31

Two new, good growing cell lines (GLC-8, GLC-11) have been established from biopsies of small cell lung cancer (SCLC). Tumor biopsies were procured by rigid bronchoscopy from tumor recurrences at the site of the primary lesions. Both tumors were clinically resistant to chemotherapy. Cytogenetic analysis revealed deletions in the short arm of chromosome 3. GLC-8 shows amplification of N-myc. Both cell lines show SCLC differentiations; neurosecretory granules were present and the SCLC related hormones dopa-decarboxylase and creatine kinase were elevated. Both cell lines behave as so-called 'classic' SCLC cell lines.
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PMID:Two small cell lung cancer cell lines established from rigid bronchoscope biopsies. 283 97

A serially xenotransplantable strain of undifferentiated embryonal rhabdomyosarcoma originating from the nasal cavity of a 42-year-old woman has been established in our laboratory. After radiotherapy for the tumor donor, distinct rhabdomyoblastic differentiation of the undifferentiated sarcoma cells appeared in the primary lesion, and it is a reasonable assumption that X-irradiation has a certain potentiality to induce morphologic differentiation of tumor cells. To study this possibility, tissue fragments of undifferentiated embryonal rhabdomyosarcoma that had grown to more than 10 mm after being transplanted to nude mice were selectively irradiated in situ. The degree of rhabdomyoblastic differentiation according to radiation dose was evaluated by light and electron microscopy and by immunostainability for myoglobin, creatine phosphokinase-MM, and desmin. Distinct morphologic differentiation of undifferentiated sarcoma cells could be induced by repeated X-irradiations at several-week intervals.
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PMID:X-radiation-induced differentiation of xenotransplanted human undifferentiated rhabdomyosarcoma. 291 Nov 82

Using a chemically defined medium containing hydrocortisone, insulin, transferrin, 17 beta-estradiol and selenium, with or without serum supplementation (2.5% v/v), continuous cell lines can be established from 72% of all fresh biopsy specimens of small cell lung cancer (SCLC) containing tumor cells. No differences were observed in the rate of establishing cell lines from newly diagnosed untreated patients, or from patients who have relapsed from prior therapy, or from a variety of different organ sites. Biochemical characterization of 50 SCLC cell lines for the expression of L-dopa decarboxylase; bombesin-like immunoreactivity; neuron-specific enolase, and the brain isozyme of creatine kinase, revealed that SCLC cell lines can be subdivided into two distinct classes: classic SCLC cell lines (35 lines), which express elevated levels of all four biomarkers; and variant SCLC cell lines (15 lines) which have undetectable levels of L-dopa-decarboxylase and bombesin-like immunoreactivity, but continue to express neuron-specific enolase and the brain isozyme of creatine kinase. The presence of the latter two markers distinguishes variant lines fron non-SCLC cell lines. In addition, four distinct classes were identified morphologically. The biomedical differences among established SCLC cell lines may account for the differences in response rates to cytotoxic therapy observed in newly diagnosed SCLC patients. A prospective study of biomarker characterization of SCLC tumors will determine if clinical differences exist between classic and variant SCLC tumors.
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PMID:Establishment and identification of small cell lung cancer cell lines having classic and variant features. 298 57

Elevated serum levels of creatine kinase (CK) were found in a patient with small-(oat) cell carcinoma of the lung. Fractionation of the enzyme showed markedly elevated CK-MB and CK-BB isoenzymes. Clinical and subsequent pathological examination showed no evidence of infarction, inflammation, or tumor involvement of the heart; however, analysis of tumor tissue for CK showed predominance of CK-MB and CK-BB isoenzymes, thus implicating tumor as the source of the circulating levels of CK-MB and CK-BB. Our case is the first to document CK-MB from neoplastic tissue homogenates, and illustrates that markedly elevated circulating levels of CK-MB, or increased levels of CK-MB in combination with CK-BB may point away from a myocardial source, and toward the existence of a malignancy.
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PMID:Elevated CK-MB and CK-BB in serum and tumor homogenate of a patient with lung cancer. 298 11

An atypical creatine kinase (CK) isoenzyme migrating cathodically to CK-MM in the electrophoresis was observed as response to the embolization of the right hepatic artery in two patients with liver metastasis. The time course of the atypical CK release was compared to that of tumor secretion products, i.e., insulin and 5-hydroxy-in-dol-acetic acid. The CK isoenzyme probably reflects a mitochondrial breakdown of the metastasis in question. The influence of the treatment on liver function was characterized by a marginal augmentation of ASAT and ALAT and by a small but significant leakage of mitochondrial glutamate dehydrogenase. In addition to the atypical CK, CK-BB, and CK-MB isoenzymes were found in the serum of the patient with primary carcinoid carcinoma.
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PMID:Creatine kinase isoenzymes: biochemical findings after therapeutical embolization of the hepatic artery in two patients with liver metastasis of an islet cell carcinoma or a carcinoid tumor. 298 64

In this paper, data are presented which demonstrate that adenylate kinase and creatine kinase are oncodevelopmental enzymes in the rat prostate. The Dunning tumor (dorsal rat prostate) was used as a model system; four sublines of the tumor (R3327-H, R3327-AT, MAT Lu, and MAT LyLu) were studied. The tumor lines were maintained as solid tumors in syngeneic rats (Copenhagen) and as monolayers in tissue culture. The appearance of adenylate kinase with malignant transformation of the dorsal prostate was demonstrated. The disappearance of the CK-M subunit of creatine kinase and decreasing levels of creatine kinase were demonstrated with increasing anaplasia. The lactate dehydrogenase (LDH) concentration increased with increasing anaplasia, and the LDH isoenzyme pattern shifted to a more glycolytic pattern (LDH-4, LDH-5). The malignant isoenzyme pattern was reversible with the use of a differentiating agent (dimethyl sulfoxide). Prostates from neonatal rats and castrated adult male rats exhibited patterns of creatine kinase and adenylate kinase similar to those of the undifferentiated tumor. The oncofetal isoenzyme pattern of the castrated rat prostate was reversible with physiological levels of exogenous testosterone.
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PMID:Oncodevelopmental enzymes of the Dunning rat prostatic adenocarcinoma. 299 72


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