Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During tumor progression, micrometastases at their earliest stages have been difficult to analyze qualitatively or quantitatively because of a lack of suitably sensitive markers to discriminate small numbers of tumor cells from normal tissue cell populations. To overcome this problem, the Escherichia coli beta-galactosidase (lacZ) gene was introduced into human EJ Ha-ras oncogene-transfected BALB/c 3T3 cells with subsequent injection of transfected cells into athymic nude mice. Using a chromogenic substrate (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside), the lacZ-bearing tumor cells at primary tumor sites as well as at secondary organs stain intensely blue and can be easily distinguished from the host tissue cells hours, days, or weeks postinjection. Staining of lacZ-bearing tumor cells is specific and extremely sensitive in detecting micrometastatic foci in lungs and other organs, including brain and kidney for the first time. Stable integration of the lacZ and ras genes into cultured cells and subsequent tumor cells was verified by Southern blot analyses. The lacZ gene appears to be a stable marker during tumor progression in vivo based both on phenotypic (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining) and on genotypic (Southern blot analysis) evidence. Furthermore, 5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining of tumor cells can also be used together with alkaline phosphatase staining relatively specific for endothelial cells to relate the topographies of metastatic cells and host blood vessels in embedded sections. By using the lacZ gene as a sensitive quantitative marker, analyses of micrometastasis development in the lung indicate that the ras oncogene contributes to the metastatic phenotype in this EJ Ha-ras model system, although further genetic and/or phenotypic alterations appear to be necessary for long-term growth and development into overt metastases. These findings demonstrate the effectiveness and sensitivity of the bacterial lacZ gene as a phenotypic marker in tumor progression studies, providing both a qualitative and a quantitative tool in virtually any tumor system for examining micrometastasis formation in target organs and the relationship of tumor cells to host organ microenvironments.
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PMID:Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression. 218 31

Patients with newly diagnosed prostatic cancer should be investigated with regard to the presence or absence of distant metastases by: (1) Clinical history especially of weight loss, recent pain, or analgesics intake. (2) Physical examination, looking especially for hepatic enlargement, peripheral lymph nodes, local bone tenderness. (3) Performance status. (4) Hemoglobin, creatinine, PSA and/or PAP, alkaline phosphatases, liver tests, testosterone. (5) Bone scan with X-ray of doubtful hot spots. (6) Chest X-ray. (7) Ultrasound scans (liver, kidney, lymph nodes) or CT scan may be indicated if abnormal blood parameters or in specific situations. (8) Other investigations are only indicated in special circumstances. Follow-up should include: (1), (2), (3), (4) every 3 months. For patients in clinical trials, depending on the end point, bone scan should be repeated every 6 months or possibly depending on the prognostic group (good: every 12 months; bad: 3 to 6 months). For routine clinical management, it could be repeated only when markers (PAP, PSA, alkaline phosphatase) show significant (25-50%) increase and provided the result will influence treatment. Other investigations should only be repeated or performed if abnormal at the start of if clinical data require them.
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PMID:The staging of M+ disease. 221 62

Leukocyte alkaline phosphatase (LAP) scores and carcinoembryonic antigen (CEA) levels were analyzed in 53 patients suffering from breast cancer. All patients underwent mastectomy and received adjuvant treatment, and all lived more than 5 years after diagnosis without metastatic disease. Thirty-three patients received adjuvant radiotherapy, and 20 patients received adjuvant chemotherapy. The median LAP score before radiotherapy was 117 +/- 48; two months after the beginning of radiotherapy this value was 175 +/- 71, being significantly higher than the original value (p less than 0.001), and one year after the beginning of radiotherapy it was 105 +/- 63, which approximated the normal scores. The median LAP score before chemotherapy was 138 +/- 69; two months after the beginning of chemotherapy it was 194 +/- 63, i.e. significantly higher than before chemotherapy (p less than 0.002), and one year after the beginning of chemotherapy it was 150 +/- 56. Median CEA levels before radiotherapy were 6.4 +/- 5.1 ng/ml; two months after the beginning of radiotherapy this value was 6.0 +/- 5.0 ng/ml; and one year later 7.4 +/- 6.2 ng/ml. Median CEA levels before chemotherapy were 8.1 +/- 12.0 ng/ml; two months after the beginning of chemotherapy 12.6 +/- 13.0 ng/ml (p less than 0.05) in comparison with the values before chemotherapy; and one year after the beginning of chemotherapy it was 8.6 +/- 5.4 ng/ml. We concluded that the LAP scores were influenced by adjuvant radio- or chemotherapy, and the CEA levels were influenced by chemotherapy.
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PMID:Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients. Influence of the treatment on the markers. 227 82

A Phase II study of the combination of etoposide (VP-16) and cyclophosphamide (CPM) was conducted in an attempt to identify active and potentially less toxic agents for treating patients with osteogenic sarcoma (OS). VP-16 was given as a 72-hour infusion for a total dose of 600 mg/m2. CPM was given as six pulses of 300 mg/m2 every 12 hours for a total dose of 1800 mg/m2. Seventeen newly diagnosed patients, including five (29%) with metastatic disease, were evaluated before and after two courses of VP-16 and CPM for clinical, radiologic, and biochemical (serum alkaline phosphatase [SAP]) responses of the primary tumor and metastases. Fifteen (88%) patients achieved complete or partial clinical responses. Fourteen (82%) patients achieved radiologic responses. Thirteen (87%) of 15 patients with higher than normal SAP levels for their age showed partial or complete responses. Three (60%) of the five patients with metastatic disease achieved complete or partial responses. The only major toxicity was myelosuppression, which led to 21 (62%) brief admissions after 34 courses of chemotherapy for intravenous antibiotic therapy for fever and neutropenia, without associated mortality. It was concluded that the combination of VP-16 and CPM is effective chemotherapy for both primary and metastatic OS. Although myelosuppression is inevitable, it is rapidly reversible in the drug dosages used. Further studies are needed to evaluate the effect of these drugs in combination with established agents in improving the disease-free survival of patients with OS.
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PMID:Response of osteogenic sarcoma to the combination of etoposide and cyclophosphamide as neoadjuvant chemotherapy. 229 54

The systemic administration of interleukin-2 (IL-2) can lead to significant antitumor responses in some patients with metastatic cancer in whom standard therapy has failed. A limitation of this immunotherapy is the toxicity associated with IL-2 infusion. To assess toxicity, we determined aspartate aminotransferase (AST; EC 2.6.1.1), alanine aminotransferase (ALT; EC 2.6.1.2), gamma-glutamyltransferase (GGT; EC 2.3.2.2), lactate dehydrogenase (LD; EC 1.1.1.27), alkaline phosphatase (ALP; EC 3.1.3.1), creatine kinase (CK; EC 2.7.3.2), total bilirubin (TBI), direct bilirubin (DBI), creatinine, urea nitrogen, and C-reactive protein in serum from 21 patients before and during five consecutive days of IL-2 treatment. Ten patients were followed for an additional five days after the end of IL-2 therapy. The IL-2 infusion caused liver toxicity and prerenal azotemia, as evidenced by significant increases (P less than 0.05) of all analytes except CK by day 1. There was a progressive increase in the results (except CK) for these tests until IL-2 treatment was stopped. Seven tests related to liver function (AST, ALT, GGT, LD, ALP, DBI, and TBI) showed increases, but the test results indicated significant improvement and moved toward the baseline value five days after the end of IL-2 therapy. Concentrations of creatinine and urea nitrogen in serum were normal three days after the cessation of IL-2 therapy.
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PMID:Changes in laboratory results for cancer patients treated with interleukin-2. 231 Dec 9

Rectal involvement from prostate cancer occurs in 1.5-11% of cases. A rarer presentation is that of a separate metastasis to the high rectosigmoid colon causing an annular stricture. We present our experience with six such cases who presented with gastrointestinal symptoms. Two of the cases had undergone intestinal resections. All 6 patients had radiographic evidence of an annular stricture in the rectosigmoid area. Retrospective review revealed evidence of metastatic disease in all cases in the form of abnormalities in one or more of the following: intravenous urography, radionuclide bone scan, liver spleen scan, acid phosphatase, or alkaline phosphatase. The mean survival was 9.3 months. This rare presentation of prostate cancer may be difficult to distinguish from primary colorectal cancer and therefore needs to be ruled out to avoid intestinal resections.
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PMID:Separate annular strictures of the rectosigmoid colon secondary to unsuspected prostate cancer. 231 6

Levels of alkaline phosphatase isoenzymes in patients with hepatic diseases, liver tumours and in normal control groups were analysed. Attention was focused on the ALP 1 isoenzyme and its validity in the diagnosis of hepatic metastases was confirmed.
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PMID:[Behavior of alkaline phosphatase isoenzymes in liver diseases]. 233 64

Alkaline phosphatase, osteocalcin and hydroxyproline levels were evaluated in patients with the following conditions: primary hyperparathyroidism, renal dialysis, hyperthyroidism, Cushing's syndrome, long term corticosteroid therapy, Paget's disease, osteoblastic metastases, osteolytic or mixed metastases, and nutritional osteomalacia. In all cases the levels of the three substances were increased, with the following exceptions: a) in endogenous or exogenous hypercortisolism states osteocalcin level was reduced and those of alkaline phosphatase and hydroxyproline were unchanged; and b) in blastic or lytic metastases osteocalcin level was unchanged. In general, alkaline phosphatase and hydroxyproline levels had a higher sensitivity than those of osteocalcin in structural bone disease (Paget's disease, blastic or lytic metastases), whereas the converse was true for endocrine bone disease (the remaining conditions except osteomalacia, which is mixed, both structural and endocrine; in this syndrome, the three substances showed the same sensitivity.
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PMID:[Different behavior of bone turnover markers in endocrine (extrinsic) and structural (intrinsic) osteopathies]. 234 91

We evaluated the serum osteocalcin and alkaline phosphatase levels and the urinary hydroxyproline excretion in patients with blastic, lithic or mixed metastases, humoral malignant hypercalcemia (HMH) and myeloma. In patients with metastasis of any type osteocalcin did not reach a significant increase although in blastic metastases an increase approaching signification was observed. However, the sensitivities of alkaline phosphatase or hydroxyproline were much higher. In HMH hydroxyproline increased to levels similar to those found in primary hyperparathyroidism. By contrast, although osteocalcin had a significant increase, its values were much lower than in parathyroid disease. The changes in alkaline phosphatase were nonevaluable. In myeloma none of the three markers changed. The major conclusion of the present study is that osteocalcin has little practical usefulness for the investigation of neoplastic patients.
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PMID:[Bone turnover markers in tumor pathology with bone involvement]. 235 62

To evaluate the incidence of a positive bone scan at presentation in women with primary breast cancer, 389 consecutive 99Tcm bone scans over a ten-year period (1978-87) were retrospectively and blindly reviewed by a single observer. The study comprised all women clinically staged I-III (UICC criteria) and irradiated with radical intent in the Professorial Unit of Radiotherapy at this institution. The initial scan was performed within six weeks of primary surgery, and was judged to show metastatic disease in only 24/389 (6%) overall. The incidence of a positive scan increased with stage from 2/80 (2.5%), and 9/226 (4%) to 13/83 (16%) for stages I, II, and III respectively. Pre-operative haemoglobin, serum alkaline phosphatase level, age, menstrual status and degree of nodal involvement were not significantly associated with the risk of a positive scan. Patients found to have a positive scan experienced a significantly shorter overall survival than those with a normal scan (p greater than 0.001). After a mean follow-up time of 46 months (range 3-120 months), 45/365 originally normal scans 15% had converted to an abnormal scan, and a further 32 patients developed radiological evidence of bone metastases.
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PMID:Skeletal scintigraphy in carcinoma of the breast--a ten year retrospective study of 389 patients. 238 28


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