Gene/Protein Disease Symptom Drug Enzyme Compound
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In two patients with renal cell carcinoma, the following biochemical changes were found independently of hepatic metastases: increased alkaline phosphatase activity, rise in bromsulfothalein retention, hypoalbuminemia, increase in alpha2-globulin, and prolonged prothrombin time (Stauffer syndrome). In both cases the syndrome was found to be the first sign of the renal cell carcinoma. In one patient liver function returned to normal after removal of the neoplasm, in correlation with the good recovery. In the other case the abnormal laboratory findings persisted after total renal surgery. Clinically, diffuse pulmonary metastases occurred. Both case histories show the high significance in knowing Stauffer syndrome and its value for early diagnosis and operative success.
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PMID:[Stauffer syndrome, paraneoplastic hepatic dysfunction syndrome associated with renal cell carcinoma (author's transl)]. 126 34

Alkaline phosphatase electrophoretic patterns characteristic of three phases in early human trophoblast development are described in this preliminary communication. Phase 1 (6 to 10 weeks) consists entirely of two heat-sensitive, L-homoarginine-inhibited bands, the slower one of which possesses antigenic determinants of live-bone-type alkaline phosphatase, whereas the fast band lacks any of the known alkaline phosphatase antigenic determinants. Phase 2 pattern (11 to 13 weeks) is that of a mixture of Phase 1 and Phase 3 isozyme components, the latter exhibiting two isozyme bands with the characteristics of term placental alkaline phosphatases correspond in order to non-Regan isoenzyme, a mixture of Regan and non-Regan isoenzymes and Regan isoenzyme in a variety of human cancer tissues. The biochemical profile characteristic of trophoblast developmental Phase 1 alkaline phosphatase is expressed as 78.5% heat-sensitive inhibition (5 min at 65 degrees), 66.3% L-homoarginine inhibition, and 17.3% L-phenylalanine inhibition where n = 12. It is hypothesized that the alkaline phosphatase of human tumor tissues reflects the expression of placental genes corresponding to one or more phases of trophoblastic development.
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PMID:Developmental phase-specific alkaline phosphatase isoenzymes of human placenta and their occurrence in human cancer. 127 31

The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer.
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PMID:The level of serum granulocyte colony-stimulating factor in cancer patients with leukocytosis. 128 Apr 90

The activity and isoenzyme profile of lactate dehydrogenase (LDH), alkaline and acid phosphatase were studied in tumors of the tongue, cheek, oral floor, soft palate and palatine tonsils (n = 100), leukoplakia (n = 7) and in the oral mucosa at corresponding sites in healthy subjects (n = 66), to develop tests for early detection, monitoring and prognosis of oral cancer. Levels of alpha-amylase and acid phosphatase were measured in saliva and blood serum of patients with oral cancer and healthy subjects. The activity of LDH and alkaline and acid phosphatase in oral malignancies were 1.5-6 times that in normal mucosa, depending on tumor site. Changes in LDH isoenzyme profile consisted in an increased level of M-subunits (LDH-4 and 5) and a decreased concentration of N-subunits (LDH-1 and 2). With regards to acid phosphatase, an increase in the activity of its tartrate-inhibited fraction was observed. An increase in LDH and alkaline phosphatase activity was registered for oral precancer (leukoplakia), too, although it was less pronounced than in cancer. Changes in LDH isoenzyme profile matched those in cancer patients. A significant increase in the activity of alpha-amylase, acid phosphatase and the latter's tartrate-inhibited fraction was registered in saliva of oral cancer patients (86-96%). The credibility of enzyme activity measurement in saliva for evaluation of response and prognosis is discussed.
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PMID:[Enzyme and isoenzyme activity in patients with malignant tumors of the oral mucosa]. 130 Jul 20

A new human extrahepatic bile duct carcinoma cell line (KMBC) was established from a serially transplanted tumor in nude mice that originated from a surgically resected tumor from a 73-year-old Japanese man; the cell line has been maintained for 5 five years. KMBC cells proliferate in a monolayered sheet with a population doubling time of 30 hours. Chromosome number was distributed in a range from 37 to 44, with modal numbers of 40 and 41. KMBC cells and the reconstituted tumor in a nude mouse showed moderately to poorly differentiated adenocarcinoma and possessed various functional characteristics of extrahepatic bile duct carcinoma. KMBC cells secreted carbohydrate antigen 19-9, tissue polypeptide antigen, carcinoembryonic antigen, ferritin, beta 2-microglobulin, fibronectin, and alpha 2-macroglobulin and produced glutamic oxaloacetic transaminase and alkaline phosphatase. KMBC is the second established cell line that originated from a human extrahepatic bile duct carcinoma in the world literature, and it will be applicable to various experiments.
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PMID:Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (KMBC). 131 90

The real need for extensive staging at the time of diagnosis is discussed in regard to small cell lung carcinoma. We performed a decisional retrospective analysis on a series of 182 patients, based on three staging steps: the first step included physical examination and routine biologic tests. The second step consisted of liver ultrasonography and needle aspiration of any clinically detectable tumor mass, and the third step included bone marrow examination, radionuclide bone scan, thoracic, abdominal, and brain CT scan. A stepwise multivariate logistic regression performed on 11 variables considered in the first step shows that a four-parameter model can predict the spread of the disease (limited or extensive): weight loss, performance status, and elevated LDH or alkaline phosphatase levels. Limited disease can be predicted in two ways: (1) elevated LDH with normal alkaline phosphatases, no weight loss, and good performance status, or (2) normal LDH and alkaline phosphatases. In this series, 28 percent of patients can be predicted as having extensive disease and can be treated with chemotherapy alone without chest irradiation. After the second step, the probability of disease being extensive is only 25 percent, and only 84 (46.15 percent) patients would need to undergo the third step of staging procedures (brain CT scan, bone marrow aspiration and biopsy, radionuclide bone scan) with this method. We conclude that a multistep approach represents a simple staging method and offers the advantage of harmlessness and lower costs for patients not to be evaluated in prospective clinical trials.
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PMID:Pretreatment staging evaluation in small cell lung carcinoma. A new approach to medical decision making. 132 12

Mild liver dysfunction is a well-known complication of HAI, but it has been thought to be transient and reversible in most cases. In the case, of metastatic liver disease, in particular, HAI has been performed safely because liver function is normal for the most part. We encountered 2 cases of irreversible severe liver dysfunction and esophageal varices after hepatectomy for metastatic liver tumor from colorectal cancer. They were treated with postoperative adjuvant HAI. Biliary enzyme as alkaline phosphatase elevated, and dilated intrahepatic bile ducts were observed in both patients. Fibrosis of Glissonean sheath, dilatation of intrahepatic bile ducts and intrahepatic biliary stones were observed at autopsy in both patients. One of the patients had obstruction of portal trunk. It must not be forgotten that such complications can occur even in a case with non-cirrhotic liver.
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PMID:[Two cases of esophageal varices complication after hepatic arterial infusion chemotherapy (HAI) for metastatic liver tumor]. 132 19

Sertoli cell intracellular protein 1 (SCc1) and 2 (SCc2) are polypeptides found in rat Sertoli cell cultures incubated with either FSH or (Bu)2cAMP. They were first identified in [35S]methionine-labeled Sertoli cell lysates using two-dimensional gel electrophoresis. Here we extend these observations by showing that SCc1 and SCc2 are present in rat seminiferous tubules, ovaries, and granulosa cells incubated with either FSH or (Bu)2cAMP and in testicular peritubular cells incubated with (Bu)2cAMP. Peritubular cells do not, however, respond to FSH with the production of SCc1 and SCc2. Peptide mapping with N-chlorosuccinimide revealed that SCc1 and SCc2 have similar cleavage patterns, suggesting a common primary amino acid sequence that is modified posttranslationally. Metabolic labeling with [32P]orthophosphate provided direct evidence that SCc1 and SCc2 are phosphoproteins. A shift in mobility of SCc1 and SCc2 toward the basic region of the gel to positions designated SCc1' and SCc2' occurred when cell lysates were treated with alkaline phosphatase before electrophoresis, providing additional evidence that SCc1 and SCc2 are phosphoproteins. SCc1 and SCc2 are also shown to be mitochondrially-associated in the Sertoli cell. Peptide maps of SCc1, SCc2, SCc1', and SCc2' obtained by treatment with alpha-chymotrypsin, are identical to proteolytic maps of proteins pp30', p30, and pp30 from adrenocortical cells. SCc1, SCc2, SCc1', and SCc2' are homologous with regard to their regulated expression, electrophoretic mobility, and mitochondrial localization to the adrenal proteins pp30' and pp30 as well as a series of 30 kilodalton proteins from MA-10 Leydig tumor cells. Both the adrenal cell proteins and the Leydig tumor cell proteins are thought to participate in cholesterol transport to the inner mitochondrial membrane, providing substrate for the cholesterol side-chain cleavage enzyme complex, an activity which the Sertoli cell does not perform, suggesting that alternative functions must be sought for SCc1 and SCc2 in Sertoli cells.
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PMID:Follicle-stimulating hormone-regulated Sertoli cell proteins SCc1 and SCc2 are phosphorylated and mitochondrially associated. 133 Apr 90

A 15-year old Black teenager came to a clinic at the University of Alabama's School of Medicine in Tuscaloosa requesting oral contraceptives (OCs). The physical examination indicated that she was in good health and the physician prescribed an OC (1 mg norethindrone and .035 mg ethinyl estradiol). 21 months later she returned complaining of yellow eyes for 3 weeks. The oral mucosa was also jaundiced. She had considerably high levels of bilirubin and alkaline phosphatase. She had no hepatitis virus antibodies. 5 months later she returned for the physical examination required to renew the OC prescription. She did not have jaundice at this time. 10 months later she complained of malaise and muscular pain. Her alkaline phosphatase level was high, but her bilirubin level was normal. She had mild hepatosplenomegaly without focal defects. After reviewing her medical records, the physician diagnosed intrahepatic cholestasis and discontinued her OC prescription. Liver function tests were normal within 3 months. 14 months later, she returned complaining of malaise and reported taking OCs obtained at another clinic 3 months earlier. The physician advised her about the complications of OCs and about other contraceptive methods. The same physician also examined a 32-year-old Black woman who had intermittent epigastric and right-upper quadrant abdominal pain for 2 weeks. Eating worsened the pain, which lasted for up to 15 minutes. She had used an OC for 12 years. Ultrasound revealed a 4.2 cm hypoechoic mass in the left upper lobe of the liver. The physician discontinued the OCs. The tumor regressed over 12 months. Active liver disease is a contraindication to OC use. Women who had cholestatic jaundice while pregnant or have first degree relatives with cholestatic jaundice of pregnancy should not use OCs. Physicians may introduce OCs to closely monitored women with a history of liver disease whose liver function tests are normal. Women with a family history of biliary excretion defects should not use OCs.
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PMID:Hepatobiliary complications of oral contraceptives. 133 97

Resistance to several cytotoxic agents, including anthracyclines, vinca alkaloids and epipodophylline derivatives (multidrug resistance, or MDR) can develop in tumor cells by overexpression of a 170-kd glycoprotein (p170) which is an essential component of a membrane transport system leading to increased drug efflux and decreased intracellular drug concentration. By means of a p170-directed monoclonal antibody (MRK-16) and immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase technique), we investigated the expression of p170 in marrow blast cells of 59 cases (38 at diagnosis and 21 in relapse) of acute-non-lymphocytic leukemia (ANLL). The proportion of strongly MDR-positive cells was higher in relapse that at diagnosis (median 15.5% vs 1.5%). Out of 31 patients who were evaluable for the results of first remission induction, failure of first-line treatment (including Daunorubicin, standard-dose and high-dose Arabinosyl Cytosine, and sometimes also Mitoxantrone) occurred in 8/22 MDR-positive cases and in 1/9 MDR-negative ones (p = 0.21). Failure of first-line treatment was always associated with a progressive increase of p170 expression. Total failures (no remission plus early relapse) were more frequent (p = 0.001) among MDR-positive cases (16/22) than among the others (2/9). These data show that MDR is very frequent in ANLL also at diagnosis and suggest that MDR can contribute to early failure of standard treatment.
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PMID:Overexpression of multidrug resistance-associated p170-glycoprotein in acute non-lymphocytic leukemia. 134 49


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