Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.2.13 (aldolase)
3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 54-yr-old man was admitted to Hokkaido University Hospital, complaining of fever, multiple arthralgia, edematous erythema and face and muscular weakness of extremities during the last 2 months. He was diagnosed as dermatomyositis by acceleration of ESR, elevation of GOT, GPT, CPK, aldolase, moderate increases of collagen fibers in biopsy specimen of skin and his clinical signs. Although stools were positive for occult blood, the routine radiographic examination failed to detect the bleeding site in the upper GI. tract. However, in the double contrast picture of the stomach, a very fine abnormal linear shadow was observed at the upper corpus of the lesser curvature. This linear shadow was a margin of the tumor, retrospectively. About 4 months later, abnormal pain occurred and a mass was palpable in the left lumbar region, suggesting a pancreatic tumor. He was operated on excising the tumor, but was performed only exploratory laparotomy because of the presence of intra-abdominal metastases. Death occurred 40 days after the operation and necropsy was done. The gross anatomical findings of the abdomen showed a stomach tumor as large as an infant's head and its metastases to pancreas, lymph nodes, and greater and lesser omentum. Esophageal mucosa including esophagocardiac junction was intact. Histological examination of the intragastric tumor revealed a typical squamous cell carcinoma with keratinization. According to the absence of the components of adenocarcinoma and squamous metaplastic gastric mucosa of non-cancerous areas in the stomach, it seemed likely to be a heterotopic squamous cell carcinoma. It was unknown about the precedence between the stomach cancer and dermatomyositis. There have been 11 cases of primary pure squamous cell carcinoma in the world literature since 1968, but this is the first case report of coexistence of these two diseases.
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PMID:[A case report of a primary pure squamous cell carcinoma of the stomach associated with dermatomyositis (author's transl)]. 726 22

On the basis of performed tests, we observed the change of pattern of pyruvate kinase isoenzyme in a malignant testicular tumor (only isoenzyme K) and the same isoenzyme in the tissue of other testis not being tumorously changed. In control group pyruvate kinase isoenzyme K and M was observed. Similarly, another pattern of aldolase isoenzymes in tumorous tissue was stated (AC) comparing with control group (arrangement AC, BC). The changes referred also to the activity of both examined enzymes in tumorous tissue and in the tissue of testis not being tumorously changed. The authors suggest the existence of a factor with depressor characteristics, which is produced by neoplasm and changes the function of genes that are responsible for synthesis examined isoenzymes in the tissue not being tumorously changed.
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PMID:The aldolase and pyruvate kinase isoenzyme patterns in a malignant testicular tumor from a 27 year old male. 731 32

Enzyme patterns characteristic of fetal tissue have been noted in some experimental tumor models, particularly in hepatomas. In this study we undertook to determine whether biochemical evidence of a similar reversion could be detected in tumors of other human organs. As marker, we chose to use the aldolase isoenzymes A, B and C, for which distinct adult and fetal tissue patterns have been described. Using monospecific antibodies, we determined the aldolase isoenzyme pattern in a variety of human organs ranging in age from 14 to 40 weeks of gestation, in the 2- to 3-month postnatal period and in adults. In addition, 19 breast cancers, 19 primary lung cancers and 8 kidney cancers were examined. Our studies on breast cancer revealed three apparently distinct groups -- one showing primarily the A isoenzyme type (6 cases), a second containing mainly A with considerable quantities of B and C isoenzymes (9 cases) and a third group (4 cases) which may contain a different isoenzyme altogether since the combined activity of the three known forms was less than 100% in each case. In lung cancer, fetal characteristics could be substantiated since in fetal and adult lung tissue, the isoenzyme pattern is almost identical; 3 out of 19 cases showed substantial quantities of the B isoenzyme. In kidney tumors, a reversion to the A form with an appreciable fraction of the C form was found, which is similar to the fetal pattern.
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PMID:Aldolase isoenzyme patterns during human ontogeny and in lung, kidney and breast cancer. 741 92

Enzymology has acquired a prominent place in human pathology, and serum enzyme investigations have become a prerequisite for various diseases, including cancer. Serum phosphohexose isomerase (PHI), aldolase (ALD) and alkaline phosphatase (ALP) levels were evaluated in 90 untreated patients with cervical carcinoma and 84 healthy age-matched females (controls). The concentrations of the three enzymes were significantly raised (p < 0.001) in patients compared to the controls. Receiver operating characteristic curve analysis revealed higher sensitivities of PHI and ALP, as compared to ALD at different specificity levels between 60 and 95%. Combined use of PHI and ALP revealed increased sensitivity and specificity. Combined use of PHI, ALD and ALP revealed a greater number of responders with enzyme values within the normal range than nonresponders. The results suggest that combined evaluation of the enzymes might be helpful to establish a useful aid to strengthen the armamentarium currently employed in the diagnosis and treatment monitoring of patients with cervical carcinoma.
Tumour Biol 1994
PMID:Combined use of serum enzyme levels as tumor markers in cervical carcinoma patients. 814 29

Glycolysis, which is the primary energy source in cancer cells, is known to be controlled by allosteric regulators, as well as by reversible binding of glycolytic enzymes to cytoskeleton. We have previously found that different calmodulin antagonists decrease the levels of allosteric activators of glycolysis, and reduce ATP content and cell viability in B16 melanoma cells. Here we report of a novel, additional, mechanism of action of calmodulin antagonists in melanoma cells. We show that these drugs cause a detachment of the glycolytic enzymes, phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13), from cytoskeleton of B16 melanoma cells. This effect was dose- and time-dependent, and preceded the decrease in cell viability. The detachment of glycolytic enzymes from cytoskeleton would reduce the provision of local ATP, in the vicinity of the cytoskeleton-membrane and would affect cytoskeleton structure. Since the cytoskeleton is being recognized as an important modulator of cell function, proliferation, differentiation and neoplasia, detachment of the glycolytic enzymes from cytoskeleton induced by calmodulin antagonists, as well as their reported inhibitory action on cell proliferation, make these drugs most promising agents in treatment of cancer.
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PMID:Detachment of glycolytic enzymes from cytoskeleton of melanoma cells induced by calmodulin antagonists. 921 7

It is known that the serum in cancer patients has the characteristics of the heat-stability. The factor produce the heat-stability is known to be due to tumor marker(TM) such as CEA, CA125(glycoprotein), CA19-9, CA15-3, SLX, CA50, CA72-4, DU-PAN-2, ST-439, SPAN-1(mucin) and alpha 1-acid glycoprotein, IAP(acute reactants). CEA belongs to IgG supergene family protein and is not oncofetal protein. CA19-9 is synthesis in subjects with Le(a) or Le(b) type, but negative in Le(a- b-) type. Thus, CA19-9 is not available as TM in Le(a- b-) type. Many TMs can be classified in 3 types because cancer cell has the character of immature cells which composed of immature proteins or glycoproteins. (1) Oncofetal protein: AFP(fetal albumin), PTHrP(fetal PTH) (2) The immature isozyme type: increase of amylase(salivary type), CPK(brain type) and aldolase (muscle and brain type) (3) The immature protein in biosynthesis process: increase of precursor protein(prepro type or pro type) such as PIVKA-II(preprothrombin), ProGRP, TPA or CYFRA 21-1(pro-keratin?) and hormone precursor in hormone producing tumor.
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PMID:[Tumor marker--present and future]. 931 Dec 62

Juvenile dermatomyositis (JDM) is characterized by microvasculopathy of the striated muscle, which indicates different etiology, clinical manifestation and prognosis from the adult-onset dermatomyositis. We experienced 10 cases of JDM and 1 case of juvenile polymyositis (JPM) in the recent 14 years, and analyzed clinical manifestation, laboratory findings, treatment anrognosis. The cases were 9 girls and 2 boys. The onset of the disease was 2 years of age in 2 patients, and 9 to 13 years of age in 9 patients. During the follow-up courses, no cases were dead or complicated with neoplasm. Skin rash was the most frequent manifestation at the onset, and facial erythema was common. Muscle weakness was observed only in 4 cases at the onset, and in all cases muscle enzymes including creatine kinase and aldolase were elevated. The clinical course was classified into three groups; monocyclic (5 cases), chronic and recurrent (4 cases), and fulminant (2 cases). Prognosis depended not on the degree of the elevated serum muscle enzymes, but on the initial therapy employed at the onset of the disease. Five cases including 2 cases of fulminant type were initially treated with methylprednisolon pulse therapy, and all of these had no recurrence. On the other hand, 6 cases were started the therapy with p.o. prednisolone. Four of them had frequent recurrences in accordance with tapering of prednisolone. These cases were effectively treated with the combination with immunosuppressants. In previous reports, JDM and JPM were reported to be a disorder which had relatively favorable prognosis. But we found that one third of the cases had chronic and recurrent courses. Methylprednisolone pulses as initial therapy may be effective in preventing the chronicity and recurrence of the disease.
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PMID:[Clinical analysis of 11 cases of juvenile dermatomyositis and polymyositis]. 1004 16

Changes in serum levels of tumor-specific fructose 1,6-diphosphate (FDP) aldolase and nontumor-specific fructose 1-phosphate (F1P) aldolase activities were analyzed in patients with hepatocellular carcinoma (HCC) to detect the damage of tumorous and nontumorous hepatic cells after percutaneous ethanol injection (PEI). Initial PEI was performed in 20 patients containing 22 HCC nodules with a diameter of < or = 4 cm. Changes in serum hepatic enzyme activities were measured before and after repeated PEI. FDP and F1P aldolase levels were measured by substrate-specific enzymatic methods. Pre- and posttreatment alpha-fetoprotein (AFP) levels were determined by radioimmunoassay. The consequent changes in the total nontumorous liver volumes after PEI were also analyzed by follow-up CT scans. Serum levels of FDP aldolase released by ethanol injection were progressively increased (P < 0.0001) until the third PEI and thereafter decreased. In contrast, serum levels of F1P aldolase were continuously elevated even after the third PEI (P < 0.0001). Serum levels of transaminases were also elevated after repeated PEI (P < 0.0001). The FDP/FIP aldolase ratio decreased significantly with increased volume (>20 ml) of injected ethanol (P = 0.01) caused by nontumorous liver damage. The elevation of FDP aldolase was markedly associated with a decrease in serum levels of AFP (P < 0.001), indicating adequate tumor necrosis. The progression of the total nontumor liver atrophy depended on the volume of injected ethanol and correlated significantly with F1P aldolase levels after PEI (P < 0.01) but not with FDP aldolase. These results demonstrated that caution is needed to avoid nontumorous liver damage caused by the large volume of ethanol injection in treating HCC. Measurement of FDP and F1P aldolase activities in serum after PEI is clinically useful to detect the degree of tumorous and nontumorous tissue damage by ethanol.
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PMID:Use of FDP and F1P aldolase to detect tumorous and nontumorous tissue damage by ethanol injection of hepatocellular carcinoma. 1049 42

Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. Glycolysis is known to be controlled by allosteric regulators, as well as by reversible binding of glycolytic enzymes to cytoskeleton. We report here that clotrimazole (l-(alpha-2-chlorotrityl)imidazole), the antifungal azole derivative, which was recently recognized as calmodulin antagonist, induced a dose-dependent detachment of the glycolytic enzymes, phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and aldolase (D-fructose-l,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13), from cytoskeleton of LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. The detachment of glycolytic enzymes from cytoskeleton would reduce the provision of local ATP, in the vicinity of the cytoskeleton membrane, and would also affect cytoskeleton structure and cell shape. We show here that clotrimazole decreased the viability of LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. After 3h of incubation with clotrimazole, complete cell destruction was detected. Ultrastructural cell damage was manifested by disintegration of the outer membrane by scanning electron microscopy (SEM). The detachment of glycolytic enzymes from cytoskeleton, induced by clotrimazole, preceded the decrease in cell viability, which indicates that this is an early effect and not a result of cell death. Since the cytoskeleton is being recognized as an important modulator of cell function, proliferation, differentiation, and neoplasia, detachment of the glycolytic enzymes from cytoskeleton induced by clotrimazole, as well as its reported inhibitory action on cell proliferation, makes this drug the most promising agent in the treatment of cancer.
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PMID:Detachment of glycolytic enzymes from cytoskeleton of Lewis lung carcinoma and colon adenocarcinoma cells induced by clotrimazole and its correlation to cell viability and morphology. 1212 31

Proposing that a blend of the chemical diversity of small synthetic molecules with the immunological characteristics of the antibody molecule will lead to therapeutic agents with superior properties, we here present a device that equips small synthetic molecules with both effector function and long serum half-life of a generic antibody molecule. As a prototype, we developed a targeting device that is based on the formation of a covalent bond of defined stoichiometry between a 1,3-diketone derivative of an integrin alpha(v)beta(3) and alpha(v)beta(5) targeting Arg-Gly-Asp peptidomimetic and the reactive lysine of aldolase antibody 38C2. The resulting complex was shown to (i) spontaneously assemble in vitro and in vivo, (ii) selectively retarget antibody 38C2 to the surface of cells expressing integrins alpha(v)beta(3) and alpha(v)beta(5), (iii) dramatically increase the circulatory half-life of the Arg-Gly-Asp peptidomimetic, and (iv) effectively reduce tumor growth in animal models of human Kaposi's sarcoma and colon cancer. This immunotherapeutic has the potential to target a variety of human cancers, acting on both the vasculature that supports tumor growth as well as the tumor cells themselves. Further, by use of a generic antibody molecule that forms a covalent bond with a 1,3-diketone functionality, essentially any compound can be turned into an immunotherapeutic agent thereby not only increasing the diversity space that can be accessed but also multiplying the therapeutic effect.
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PMID:Chemically programmed monoclonal antibodies for cancer therapy: adaptor immunotherapy based on a covalent antibody catalyst. 1270 56


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