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 42-year old male was found to have adenocarcinoma of the lung and very high serum alkaline phosphatase levels. The clinical course and autopsy excluded the possibility that the enzyme elevation was due to liver or bone metastases, which is the most common cause for such a phenomenon. It was proven that the tumor secreted the alkaline phosphatase, and that the latter could serve as a marker of its recidivation. Although the phenomenon of tumors secreting alkaline phosphatase is not new, including some types of lung carcinomas (such as squamous cell and epidermoid), it is, to the best of our knowledge, the first time adenocarcinoma of the lung was found to secrete the enzyme.
 ...
PMID:Adenocarcinoma of the lung secreting alkaline phosphatase. 51 43

Chromomycin A3 was given to 43 patients with metastatic cancer in order to determine the tolerable dose when the drug was administered on an every-other-day dose schedule for a total of five iv push injections, with the course of therapy being repeated every 4 weeks. At least three patients were entered at each dose level, graduated in 0.1-mg/m2 increments between 0.7 and 1.6 mg/m2. The most common (19 patients) side effect was nausea and/or vomiting, but this was usually mild, lasted for a few hours, and diminished in severity with repeated injections. Skin necrosis due to drug extravasation was a problem early in the study, but was eliminated by injecting the drug through iv tubing. Transient elevations in SGOT and alkaline phosphatase levels were observed, but proved not to be of serious consequence. Renal toxicity proved to be the limiting factor in therapy. However, a dose level of 1.3 mg/m2 was found to be a tolerable level of drug administration in previously untreated patients. Objective tumor responses were noted in four patients (Hodgkin's disease, embryonal rhabdomyosarcoma, adenocarcinoma of the lung, and malignant melanoma).
 ...
PMID:Phase I alternate-day dose study of chromomycin A3. 103 32

CB3717 is a quinazoline antifolate whose cytotoxic activity is mediated by inhibition of thymidylate synthase (TS). A phase I clinical trial commenced in September 1981 and 99 patients have received 296 treatments. Doses were dissolved in 0.15 mol/L NaHCO3 (pH 9.0) at a concentration of 4 mg/mL infused over one hour or in a total volume of 1 L infused over 12 hours. Doses were repeated every 3 weeks. The starting dose of 140 mg/m2 was escalated to 600 mg/m2. Renal toxicity, detected by a decrease in the 51Cr EDTA clearance, was dose-related and occurred in seven of ten patients receiving greater than 450 mg/m2. Reversible hepatic toxicity often associated with malaise occurred in 223 of 288 assessable courses (77%). Fifty-nine courses (20%) were associated with increases in alanine transaminase (ALT) levels to greater than 2.5 times the upper limit of the normal laboratory range. Increases in alkaline phosphatase levels also occurred, but were less marked. The severity and prevalence of these elevations were unaffected by the duration of the infusion. A self-limiting rash appeared in 12 patients and a radiation recall reaction was seen in two. Leukopenia developed in 17 patients (WBC less than 3 X 10(9)/L), and thrombocytopenia occurred in six patients (platelets less than 100 X 10(9)/L). The mean leucocyte nadir occurred on day 10 and was followed by recovery at 11 to 19 days. Neither the incidence nor the severity of any of these latter toxicities was dose related. The maximum tolerated dose was in the region of 600 mg/m2 with renal toxicity being dose limiting, although the inter-patient variation did not allow a precise definition. Seventy-six patients were evaluable for response. Responses occurred at doses greater than or equal to 200 mg/m2 and were ovary, one complete response (CR), one partial response (PR), seven minor responses (MR) in 30 cases; breast, two PRs and one MR in eight cases; adenocarcinoma of the lung, one MR in 5 cases; mesothelioma, one PR in five cases; and colon, two MRs in four cases. CB3717 has activity in heavily pretreated patients. The recommended phase II dose for good-risk patients is 400 mg/m2 using the one-hour infusion schedule of administration.
 ...
PMID:A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717. 373 49

In contrast to its absence in normal and hyperplastic bronchial mucosa, gamma glutamyl transferase (GGT) has been demonstrated on the luminal surface of adenocarcinoma cells of bronchogenic cancer in three cases studied. On the other hand, little or no GGT was demonstrable in four epidermoid carcinomas and one oat cell cancer. Metaplastic alveolar cells appearing as cuboidal epithelial cells were uniformly positive for GGT and L-homoarginine-sensitive alkaline phosphatase. Whereas interest in GGT has centered in the past on experimental hepatocarcinogenesis, the current results demonstrate an ectopic expression of GGT in metaplastic alveolar cells and in adenocarcinoma of the lung. These findings merit further exploration to document the extent of the expression of GGT in bronchogenic cancer and to attempt to explain its presence in alveolar cell metaplasia.
 ...
PMID:Demonstration of gamma-glutamyl transferase, alkaline phosphatase, CEA and HCG in human lung cancer. 611 35

High alkaline phosphatase (ALP) activity was found in the cerebrospinal fluid of a patient with intracranial metastases from adenocarcinoma of the lung. On agarose gel electrophoresis of the major ALP isoenzyme found in the cerebrospinal fluid, its mobility was different from those of the usual serum ALP isoenzymes. This abnormal mobility might be due to the linked glycan phosphatidylinositol anchor in the ALP molecule, as the mobility became the same as that of the common liver type ALP after treatment with phosphatidylinositol specific phospholipase. The immunochemical antigenicity of the cerebrospinal fluid ALP was identical with that of the common serum liver type ALP, but its sugar moiety was similar to the membranous liver-type ALP rather than the serum liver type ALP. The molecular size of the cerebrospinal fluid ALP was 140 kilodaltons, 12 less than the common serum liver type ALP, suggesting that the ALP in the patient's cerebrospinal fluid was derived from the intracranial metastatic carcinoma.
 ...
PMID:Abnormal alkaline phosphatase of hepatic type in cerebrospinal fluid of a patient with intracranial metastasis from lung cancer. 825 99

A 79-year-old woman with adenocarcinoma of the lung almost fully obstructing the right main bronchus and with multiple bone and brain metastases was admitted to our hospital in March 2005. Irradiation was considered to be successful. Since subsequent vinorelbine chemotherapy was futile, it was changed to gefitinib in June. A week after gefitinib therapy, serum alkaline phosphatase (ALP) began to increase from about 400 IU/l to 1247 IU/l, to 3470 IU/l after two weeks, and up to 3527 IU/l after three weeks. The levels then decreased to within the normal range after nine weeks. ALP isozyme showed a peak composed of ALP2 and ALP3, and the levels of other enzymes (GOT, GPT, gamma-GTP) were normal. Hence, increased ALP was thought to be derived from the bones. The patient's performance status and metastases improved during this phenomenon. Bone scintigraphy findings one month after beginning gefitinib therapy worsened, but improved after four months. Bone ALP represents osteoblastic activity. We believe that in this case bone formation became dominant because of the favorable response to gefitinib therapy.
 ...
PMID:[A case of lung cancer with alkaline phosphatase flare phenomenon during gefitinib therapy]. 1818 43