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

Weekly intragastric application of N-nitrosobis(2-oxopropyl) amine (BOP) at a dose of 10 mg/kg body wt induced prostatic cancer in 5 out of 15 MRC rats. Hyperplasia and metaplasia of the prostatic gland were found in 13 rats with or without cancer. All tumors had developed in the dorsal lobe, had reached a size of up to 20 mm and were invasive. Distant metastases were not observed. Although hyperplastic lesion were of a glandular type, all carcinomas had squamous cell character. All cases of prostatic cancer were associated with papillomas or carcinomas of the urethral epithelium, which had initially developed in the colliculus seminalis. The induction of prostatic cancer for the first time by a systemic application by a nitrosamine provides a promising model for understanding basic principals of prostatic cancer.
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PMID:A new prostatic cancer model: systemic induction of prostatic cancer in rats by a nitrosamine. 617 36

Coronavirus-like particles are found within the cytoplasm of NPC tumor cells, within the cytoplasm of the tumor cells of the regional metastases, and within tumor cells grown on nude mice. For the immunologic identification of the coronaviruses, the cultures of human tracheal epithelium (MRC-C) were used and inoculated with a known coronavirus strain. Whereas blood sera from NPC patients (n = 73) contain significantly elevated antibody titers against corona viruses, unselected sera from patients without NPC showed a low antibody titer (n = 83). Only patients suffering from infectious mononucleosis (n = 40) showed a titer pattern similar to that of NPC patients. For demonstration of antigen-antibody reaction within the NPC tumor cell cytoplasm, sera with a high antibody content against coronaviruses deriving from other than NPC patients or anticoronavirus sera from rabbits were used. By indirect immunofluorescence, the NPC tumor cells showed a bright cytoplasmic fluorescence. No fluorescence was seen when tumor cells were exposed to human sera with known low or absent corona antibody titer or to normal rabbit sera. The results indicate that next to a DNA virus infection (EBV), an RNA virus infection (coronavirus) may play a role in NPC as well as in infectious mononucleosis.
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PMID:Coronavirus-associated antibodies in nasopharyngeal carcinoma and infectious mononucleosis. 626 32

DDT is a pesticide used in malaria-control programmes throughout the world. Its potential carcinogenicity was studied in MRC Porton rats (Wistar-derived) which received dietary concentrations of 0, 125, 250 and 500 parts per million DDT (technical-grade) for life. The treatment had no adverse effects on body growth or survival rate. Various types of tumours were observed in animals in all groups: exposure to DDT resulted in statistically significant increased incidence of liver-cell tumours only in female treated rats; one such tumour was observed in control rats. No metastases of these tumours were found.
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PMID:Effects of long-term intake of DDT on rats. 628 Mar 47

At present patients in whom a testicular germ cell tumour in clinical stage I is diagnosed have a long-term survival rate of 98%. For non-seminomatous germ cell tumours in this stage three different treatment options are available: primary retroperitoneal lymphadenectomy (PRLA), the wait-and-see strategy, and primary adjuvant systemic chemotherapy. These therapeutic approaches do not obviously differ in the long-term survival rate of the patients. Abdominal CT scans yield false-negative results in 20-30% of patients with occult metastases. The identification of certain histological characteristics within the primary tumour (vascular and/or lymphatic invasion, presence of embryonal carcinoma, absence of yolk sac elements) allows stratification of patients into groups at high and low risk for tumour progression and/or the presence of retroperitoneal lymph node metastases. The determination of biological and genetic characteristics of the primary tumour in addition to classic histological parameters, does not actually seem to reveal any further prognostic information relating to the biological behaviour of the individual tumour. Therefore, with regard to the outcome of prospective and retrospective MRC studies, patients should be stratified according to the Freedman score into groups at high and at low risk of tumour progression and consequently undergo an aggressive (retroperitoneal lymphadenectomy/systemic chemotherapy) or less aggressive (wait-and-see) treatment adjusted to the aggressiveness of the individual tumour. Prospective studies should be performed to find whether biological characteristics of the primary tumour might reveal any additional prognostic information superior to that yielded by histological parameters and possibly allow an even more subtle classification of the patients into high- and low-risk groups.
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PMID:[Effect of biological prognostic factors on therapy of non-seminomatous stage I testicular tumors--an assessment of the current status]. 885 47

With overall cure in excess of 95%, there is a debate about how to conduct further trials. Three areas are reviewed: (1) Relapse and high risk patients. With a plethora of new drugs and high dose salvaging one in three second-line failures, there is plenty of choice. Substituting taxol for etoposide in etoposide, ifosfamide and cisplatin (VIP), followed by high dose, is one possibility. (2) For low-risk metastatic disease the current priority is to recruit large numbers to the EORTC/MRC three vs four courses bleomycin, etoposide and cisplatin (BEP) and 3 vs 5 day etoposide trial to evaluate the safety of risking less toxic treatment. (3) For stage 1 disease, non-seminoma, quality of life assessments and evaluating patient participation in decisions about adjuvant therapy are the principal priorities. For seminoma one course carboplatin, the first realistic alternative to radiotherapy, is currently being tested in a MRC trial. During the next decade there will be two areas of interest in addition to those above. Firstly, trials of testis conservation to reduce the use of orchidectomy on diagnosis. For advanced drug-resistant disease, gene therapy using candidate genes found to be responsible for a chemotherapy response, and exploration of their role within non-germ cell cancer.
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PMID:Future trials in germ cell malignancy (GCM) of the testis. 915 84

We used Transwell chambers to study separately cellular motility and invasion. In order to assess the cellular motility, polycarbonate microporous filters were coated with extracellular matrix proteins which adsorbed on the filters without clogging the pores. To investigate the invasive behavior of tumor cells, filters were covered with a layer of Matrigel which clogged the pores. The motility and the invasion of breast cancer cell lines (MDA-MB-231, MCF-7/6 and MCF-7/AZ cells) were assessed quantitatively in different culture media: defined (serum-free), serum-containing and normal human fibroblast MRC-5 conditioned media. In serum-containing medium, tumor cells migrated and invaded through the coated and covered filters. Their motility and invasion potentials were considerably lower in defined medium, whereas medium conditioned by MRC-5 fibroblasts stimulated both motility and invasion but not growth. The MRC-5 conditioned medium induced also the spreading of clusters of MCF-7/6 cells grown on Matrigel-coated plates.
Clin Exp Metastasis 1998 Feb
PMID:Effect of MRC-5 fibroblast conditioned medium on breast cancer cell motility and invasion in vitro. 951 1

The 5-year survival rate for patients with non-small cell lung cancer (NSCLC) who undergo complete surgical resection is only 40-69%, depending on the stage. It is well known that distant metastatic disease is the dominant site of recurrence in such patients and this observation served as the basis for trials of postoperative systemic therapy. The earliest trials of adjuvant chemotherapy, which consisted of single alkylating agents, did not achieve this goal or, even worse, showed a detrimental effect on survival. The introduction of more active drugs, such as cisplatin and vinca alkaloids, made it possible to obtain more promising results in terms of delayed recurrence of the disease. A recent meta-analysis of all randomized trials with accrual from January 1965 to December 1991 showed that the absolute risk of death was reduced by 3% at 2 years and by 5% at 5 years for patients who were treated with postoperative cisplatin-containing regimens compared with patients who were treated with surgery alone. Although the results of this meta-analysis suggest that postoperative cisplatin chemotherapy regimens may result in a slight survival improvement, adjuvant chemotherapy in NSCLC cannot be considered a standard therapy, and it is important that large, carefully conducted, randomized trials are performed in this group of patients. Four such randomized trials are being conducted in Europe. One of them, the ALPI trial, recently completed its accrual with 1200 patients. The IALT, ANITA, and MRC trials are still ongoing. The results of such trials are eagerly awaited and it is hoped that, once the value of postoperative chemotherapy is well ascertained, future developments can further improve results of combined treatment. In such direction, the recently reported results of PORT meta-analysis evaluating the role of radiation therapy are of great contribution in selecting a suitable population for future studies. In fact, only patients with pN2 disease seem to have a beneficial effect in terms of survival, especially if they have a good performance status, while radiotherapy is not justified in N0-1 patients. The optimal integration of chemotherapy and radiation therapy when both therapies are indicated represents another goal for future research.
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PMID:Consensus conference on medical treatment of non-small cell lung cancer: adjuvant treatment. 1246 43

Despite a high cure rate in men with testicular cancer, some men in the poor-prognosis group have a less favourable outcome. Poor-prognosis non-seminomatous germ-cell tumours (NSGCT) are defined as those with high tumour markers, non-pulmonary visceral metastases or a mediastinal primary site at presentation. When treated with standard chemotherapy regimens, such as bleomycin, etoposide and cisplatin (BEP), cure rates of less than 50% have been achieved in an international pooled analysis. Some strategies aimed at improving results include the use of multi-agent regimens (e.g. POMB/ACE), intensive-induction chemotherapy (e.g. CBOP/BEP), new chemotherapy drugs, such as ifosfamide, gemcitabine, oxaliplatin, paclitaxel, high-dose chemotherapy, including autotransplantation. To date, no schedule has been proven to be better than standard BEP in randomised trials. We will review the published data relating to first-line and salvage treatment of poor-prognosis NSGCT. To advance the management of this disease, physicians treating poor-prognosis disease are urged to support multi-centre trials, such as the recently launched MRC TE23 study comparing BEP and CBOP/BEP.
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PMID:The management of poor-prognosis, non-seminomatous germ-cell tumours. 1623 42

Purpose. To report the outcome of 37 patients with metastatic osteosarcoma entered into a large randomized trial (EOI 80831/MRC B002) comparing two different regimens of chemotherapy in patients with osteosarcoma.Methods. Patients with biopsy-proven osteosarcoma localized and metastatic, age 40 years or younger, were randomized to receive either two-drug treatment with doxorubicin/cisplatin (DOX 25 mg m(-2) day(-1) x 3 + DDP 100 mg m(-2) on day 1 q 3 weeks x 6 courses) or three-drug treatment comprising high-dose methotrexate (HDMTX 8 mg m(-2) administered every 4.5 weeks x 4 courses) given 10 days before DOX/DDP.Results. Twenty-four patients with metastatic disease received the two-drug arm treatment and 13 received three-drug treatment. Despite chance imbalance in numbers, there were no major differences in age, sex, primary site or performance status. Baseline alkaline phosphatase (AP) was elevated more frequently (96 vs 42%) in the two-drug arm. Twenty-one of 24 patients in the two-drug arm and 11/13 patients in the three-drug arm had evaluable primary tumors concurrent with metastases. Respective clinical response rates for the two- and three-drug arms were 48% and 40% for primary tumors, and 33% and 55% for metastases. Respective survivals at 2 and 4 years were 36% and 9% for the two-drug arm, and 69% and 52% for the three-drug arm, and survival was better for patients with normal AP at presentation. When adjusted for AP, survival was not significantly different between the two treatments (hazard ratio 0.52, 95% confidence interval 0.22-1.23, p = 0.14). There were three long-term survivors among the metastatic patients, all of whom received the three-drug therapy.Discussion. It is likely that random bias in the population (small numbers, imbalance in size of groups, uneven distribution of AP) accounts for the difference in outcome favoring the three-drug treatment in patients with metastatic disease. More reliance can be placed on the finding that disease-free and overall survival in the adjuvant component of this study (Bramwell et al., J Clin Oncol 1992; 10: 1579-91) were better after two-drug treatment.
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PMID:A Randomized Comparison of two Short Intensive Chemotherapy Regimens in Children and Young Adults With Osteosarcoma: Results in Patients With Metastases: A Study of the European Osteosarcoma Intergroup. 1852 Dec 18

Increased cyclooxygenase (COX-2) expression in tumors is known to be correlated with tumor invasion, angiogenesis, resistance to apoptosis, and suppression of host immunity. We previously reported that the invasiveness of human oral squamous cell carcinoma (OSCC) cell lines NA and HSC-4 was suppressed by treatment with either NS-398, a selective COX-2 inhibitor, or COX-2 antisense oligonucleotide (AS). In the present study, to explore the effects of COX-2 inhibition on the interaction between cancer cells and fibroblasts, we examined the effects of these anti-COX-2 reagents on the expression of matrix metalloproteinases (MMPs) in fibroblast cell lines WI-38 and MRC-5. Western blotting and enzyme-linked immunosorbent assay revealed that NS-398 and COX-2 AS down-regulated the expression and secretion of MMP-2 and the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human fibroblast cell lines. Furthermore, invasion activity of OSCC cells was down-regulated by the addition of culture supernatant from fibroblasts treated with anti-COX-2 reagents in a Matrigel invasion assay. These results suggest that selective COX-2 inhibition suppresses the invasion activity of OSCC cells via down-regulation of an MMP-2-activating mechanism involving TIMP-2 and production of the MMP-2 protein by an interaction between cancer cells and stromal fibroblasts. Genetic or pharmacological inhibition of COX-2 may therefore be a beneficial strategy in the treatment of OSCC.
Clin Exp Metastasis 2009
PMID:Inhibition of cyclooxygenase-2 suppresses the invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 production and activation. 1924 Nov 24


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