Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A pilot study was designed to evaluate the efficacy of high-dose FUDR administered through the hepatic artery for the treatment of cancer involving the liver. Three dose schedules were used beginning with a dose of 0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 2 weeks (schedule A). Elevation of serum bilirubin was the sole indication to deescalate to schedule B (0.3 mg FUDR/kg/day for two weeks followed by saline infusion for 4 weeks). Tolerance to this schedule escalated the patient to schedule C (0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 4 weeks). Eighteen patients were treated, sixteen with metastatic colon cancer, one with metastatic leiomyosarcoma, and one with hepatoma. The patient with hepatoma developed progressive disease after one cycle of therapy. Of the 17 patients with metastatic cancer only 5 patients failed therapy yielding a 70% response rate. High-dose FUDR was well tolerated with only six patients requiring deescalation to schedule B. Elevation of alkaline phosphatase and glutamic oxaloacetic transaminase was universal. Two patients developed peptic ulceration. Sclerosing cholangitis was not observed. We conclude that high-dose FUDR administered through the hepatic artery is as safe as conventional dose infusion therapy but probably not more effective. The safety of high-dose FUDR infusion therapy suggests that sclerosing cholangitis is association with hepatic arterial infusion therapy is not related to the FUDR dose.
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PMID:Good tolerance to high-dose hepatic arterial infusion therapy. 294 73

The antispermatogenic effects of 2, 4-dinitro-6-tert-. butylphenyl methanesulfonate (HE-166) were studied in Sprague-Dawley rats. They were fed 25, 100 and 400 ppm of HE-166 in the basal died for one year. Laboratory data showed no significant changes except for increases in gamma-globulin, alkaline phosphatase, GOT and GPT values in the 100 ppm group. Macroscopically, significant changes were found in the testes in the experimental group, which showed marked atrophy. Histologically, the testes were filled with fibrin exudate in the stroma and there was reduced spermatogonia, cellular debris and giant cells, and even calcification, depending on the dose of HE-166. The anti-fertility effects of HE-166 were also observed by mating rats and checking the pregnancy rate during three generations. These effects might be due to the direct cytotoxic effect of HE-166 on post-meiotic cells as epididymal spermatozoa and testicular sperm and spermatids. As far as tumor incidence was concerned, one case of fibroadenoma of the mammary gland, one case of leiomyosarcoma in the uterus in the 100 ppm group and one case of leiomyoma in the uterus in the 25 ppm group developed at around 8 months, but no other tumors developed.
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PMID:The antispermatogenic effect and toxicity of 2, 4-dinitro-6-tert-butylphenyl methanesulfonate on Sprague-Dawley rat. 609 Jun 86

A case of hepatic leiomyosarcoma is reported and the literature on smooth muscle tumors of the liver is reviewed. All 15 patients with hepatic leiomyosarcoma presented initially with hepatic or abdominal mass. About half of these patients also had abdominal pain or weight loss or both. Elevated levels of serum alkaline phosphatase, SGOT, and lactic dehydrogenase were frequent but inconsistent findings. The prognoses appeared grave, but potentially curable. All but four patients died in less than 3 years. One patient was not followed. The three patients who were alive in follow-ups survived 8 months, 1 year, and 6.5 years, respectively, with no evidence of disease. All three surviving patients had resectable tumor and were surgically treated.
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PMID:Hepatic leiomyosarcoma. 636 91

Insidious and progressive right heart failure of obscure origin warrants differential diagnosis of primary sarcoma of the pulmonary artery in patients of both sexes and 20 years of age and older. We report a case of primary leiomyosarcoma of the pulmonary truncus in a 67 years old woman. She had been well in general until when she started having fluctuating and progressive right heart failure three years ago. Clinical data included systolic murmurs in the pulmonary valve area, right ventricular hypertrophy, diminished x-ray density of the pulmonary vasculature, moderate elevation of serum LDH, alkaline phosphatase, and uric acid, and prolonged or unobtainable circulation time from the arm to lungs. The immediate cause of death was attributable to right heart failure due to pulmonary arterial stenosis caused by a locally invasive leiomyosarcoma apparently arising in the pulmonary truncus. Contributing to this right heart failure were 280 ml of serosanguinous pericardial effusion and fibrinous pericarditis.
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PMID:Leiomyosarcoma of pulmonary truncus. 648 1

Apoptosis is a physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) Receptor (FasR) and programmed or active cell (PCD) death was studied in childhood astrocytomas (ASTRs) with varying stages of malignancy, including pilocytic ASTR, low grade ASTR, anaplastic ASTR, and glioblastoma multiforme (GBM). The great majority of childhood glial tumors, particularly ASTRs express FasR whereas normal cells in the central nervous system (CNS) do not. FasR represents a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within ASTRs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with antibodies developed against FasR. Presence of FasL was also detected in childhood glial tumors. The expression of both FasR and FasL was also observed within the same ASTRs. Therefore, spontaneous, IP regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood glial tumors. During a systematic, immunocytochemical screening of 42 childhood ASTRs tissues divided according to WHO classification: 6 WHO grade I or pilocytic ASTRs; 14 WHO grade II or low grade ASTRs; 16 WHO grade III or anaplastic ASTRs and 6 WHO grade IV or glioblastoma multiforme (GBM), we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: +2 to +4, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR was present on 70% to 90% of tumor cells in pilocytic ASTRs, in 50% to 60% of the tumor cells in low grade ASTRs, in between 30% and 40% of the tumor cells in anaplastic ASTRs, and in between 20% to 35% of GBM cells. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colonic epithelium. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent immunocytochemical results. A broad spectrum of neoplastic cells have been identified to express FasR: 1) carcinomas of epithelial origin, such as breast (ductal invasive, lobular invasive, mucinous), renal cell, gastric, colorectal, endometrial, prostate, pancreas, hepatocellular and large cell and squamous cell lung carcinomas: 2) non-epithelial neoplasms such as B cell mediastinal B cell and nodal non-Hodgkin's lymphomas large granular lymphocytic leukemia of T or NK cell origin malignant fibrous histiocytoma, malignant mesothelioma, leiomyosarcoma, epitheloid sarcoma and alveolar soft part sarcoma, as well as melanomas. Flow cytometry studies have also detected FasR expression on cells of adult T cell, and hairy cell leukemias, as well as in chronic B cell lymphocytic leukemia (BCLL). The coexpression of both FasR and FasL on several malignant cell types may represent an effective mechanism of tumor escape from the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching the signal transduction associated with FasL-FasR coupling from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) may represent a new and exciting type of immunotherapy in the treatment of primary childhood glial tumors.
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PMID:Fas (Apo-1, CD95) receptor expression in childhood astrocytomas. Is it a marker of the major apoptotic pathway or a signaling receptor for immune escape of neoplastic cells? 1058 78

The authors describe a primary sarcoma of the brain with immunohistochemical and ultrastructural features of leiomyosarcoma as well as epithelioid hemangiosarcoma. The leiomyosarcomatous component consisted of spindle cells with well-developed external lamina, subsarcolemmal densities composed of microfilaments, pinocytic vesicles, and abundant intermediate filaments, and showed immunohistochemical reactions for smooth muscle actin. The epithelioid part of the tumor contained scattered cells reactive for alkaline phosphatase as well as CD31 and factor VIII. Many epithelioid cells were lipidized and remarkably similar to "stromal cells" of a hemangioblastoma. Occasional Weibel-Palade bodies, indicating endothelial differentiation, were present in scattered neoplastic cells. There were also cells with features intermediate between endothelium, pericytes and smooth muscle cells, and undifferentiated mesenchymal cells. The brain at the periphery of sarcoma showed conglomerates of well-differentiated capillaries, telangiectasias and small dysplastic arteries, features that raise the possibility of origin of this tumor from a preexisting vascular developmental abnormality.
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PMID:Primary composite angiogenic leiomyosarcoma-epithelioid angiosarcoma of the brain. 1107 73

A 72-year-old woman with von Recklinghausen's disease was referred to our hospital because of pain and muscle weakness in her thighs. She had elevated serum values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase. Based on these results, a diagnosis of polymyositis was made. Treatment with prednisolone improved muscle strength, and laboratory values returned to normal. Computed tomography, magnetic resonance imaging of the abdomen, and 131I-metaiodobenzyl guanidine MIBG scintigraphy demonstrated a tumor 3 cm in diameter in the region of the left adrenal gland. Endocrinologic investigation disclosed elevation of serum and urine catecholamines. Since the blood pressure was normal, nonfunctioning pheochromocytoma was diagnosed clinically. The nonhypertensive course was attributed to reduced vascular response to noradrenaline. Serum lactate dehydrogenase. alkaline phosphatase. and asparate aminotransferase became elevated, and abdominal computed tomography showed a well-defined mass measuring 13 x 12 x 10 cm in the right lobe of the liver. The patient underwent right trisegmentectomy and left adrenalectomy. Histologically the adrenal tumor was a typical pheochromocytoma. The hepatic tumor was a leiomyosarcoma consisting of elongated spindle-shaped atypical cells arranged in intersecting bundles. Immunohistochemically, the cells of this tumor were reactive for alpha-smooth muscle actin and vimentin. The leiomyosarcoma recurred and metastasized to the liver. Eight months after onset of symptom, the patient developed hepatic coma and died. The mean age at presentation with pheochromocytoma in von Recklinghausen's disease patients age is 42 years. Our patient was considerably older. To the best of our knowledge this is the first report of a patient with von Recklinghausen's disease developing polymyositis. asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma and illustrates the need to remain aware of the possibility of cancer in von Recklinghausen's disease.
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PMID:[A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma]. 1523 55

A 53-year-old male patient was admitted to our hospital with abdominal pain in the right upper quadrant. There was no change in laboratory investigations other than a slight increase in serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT). Computed tomography (CT) of the abdomen showed multiple hepatic nodular lesions in the liver. Tru-cut biopsy of the lesions was reported as well-differentiated neuroendocrine carcinoma. The patient received sandostatin treatment. After a few days, the patient was hospitalized in the intensive care unit with disturbance of consciousness and clinical features suggestive of encephalopathy. Serum ammonia level was found highly elevated. After the treatment with L-ornithine-L-aspartate, a remarkable improvement in the level of patient's sensorium occurred as well as a reduction in serum ammonia level within a few days. Transarterial chemoembolization (TACE) was performed one week later. The patient's condition began to worsen along with increase in serum ammonia level and he died because of hyperammonemic encephalopathy. There are case reports of hyperammonemia with some malignancies such as multiple myeloma, plasma cell leukemia, and leiomyosarcoma, or in some patients who have received chemotherapy. This case may suggest an association between hyperammonemia and neuroendocrine tumors.
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PMID:Hyperammonemic encephalopathy in a patient with primary hepatic neuroendocrine carcinoma. 1903 Oct 17

Some tumors are known to produce alkaline phosphatase (ALP). Seven cases of uterine leiomyosarcoma were identified from the clinical records of Sakai City Medical Center from January 2006 to December 2014. Patients' ages ranged from 47 to 75 years (median: 58). Clinical stages were IB, IIB, IIIA, and IVB in four, one, one, and one cases, respectively. Of these, two were found to have hyperphosphatasemia before surgery, and the elevated ALP level decreased after surgery, and increased with disease recurrence. In the cases of hyperphosphatasemia, leiomyosarcoma cells showed positive staining for ALP. There was no correlation between serum ALP and lactate dehydrogenase, or ALP and cancer antigen 125. The combination of ALP, lactate dehydrogenase, and cancer antigen 125 may be more useful for diagnosis and follow-up of leiomyosarcoma.
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PMID:Hyperphosphatasemia in leiomyosarcoma of the uterus: Two case reports and a literature review. 2869 Dec 61