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)

A unique case of a metastasising choriocarcinoma, inadvertently transplanted to a man from a female cadaver kidney is reported. When the kidney was removed six days after transplantation, arterial blood vessel infiltration by chorio-carcinoma cells and high levels of human chorionic gonadotropin (HCG) in the serum of the recipient indicated an haematogenous dissemination of viable neoplastic cells. The immunosuppressive therapy was discontinued after removal of the graft and the HCG levels in the recipient gradually decreased over a periode of eight weeks, indicating a slow immunologic rejection of the tumor cells. The recipient committed suicide seven months after the transplantation had failed. No metastases were found at a legal autopsy. It seems advisable, whenever there is evidence that neoplastic cells might have been transfered by a homograft, to remove the graft and discontinue the immunosuppressive therapy. Neoplastic cells already disseminated can still be eliminated when the immunologic system is intact and not suppressed.
 ...
PMID:Metastatic choriocarcinoma transplanted with cadaver kidney: a case report. 33 64

Within the framework of a longitudinal study, 127 chimney sweeps from the area of Upper and Middle Franconia (Bavaria, Germany), who had participated in a first medical check-up in 1974, were offered follow-up examinations in 1990. Eighty-one subjects participated in these examinations; in addition individual occupational case histories and medical case histories were obtained for a further 15 and 35 chimney sweeps, respectively. Five test subjects had died before the evaluation deadline (August 15, 1990). The causes of death were a non-Hodgkin's lymphoma, a bladder carcinoma, pulmonary metastases with unknown primary tumour, a suicide and an acute myocardial infarction. Conspicuous results were carcinoma of the oesophagus in one case and leucoplakia of the mucous membranes in the mouth and pharyngeal region in three cases; furthermore one chimney sweep had two haemorrhagic lumps on his vocal cords. Taking into account important non-occupational hazards (alcohol and nicotine abuse) as possible causes of these changes and the lack of relevant occupational exposure to products of incineration over a number of years, none of these cases nor any of the other ascertained results could be considered likely to be causally related to occupational activities. Due to the small number of cases, an epidemiological risk evaluation did not seem useful. Comparison with the results of other chimney sweep studies published in the international literature is not helpful due to the differences in study design, the varying case frequencies, and the different conditions of exposure.
 ...
PMID:Investigations on health hazards of chimney sweeps in Germany: results of a follow-up study. 139 14

Two nearly identical cases with about 100 multicentric disseminated neuroendocrine carcinomas of the skin are presented. In the Merkel cell tumors a for epithelial cells specific antigen (MAM-6) was found by immunohistochemical methods. Only in one patient generalized metastases arose after a four year course of the disease. The other patient committed suicide after a three year course of the disease. At autopsy no metastases were seen. We assume these diseases to be a systemic proliferation of malignant neuroendocrine differentiated epithelial cells, for which the term "cutaneous Merkeliomatosis" is proposed.
 ...
PMID:[Disseminated neuroendocrine cancers of the skin--a cutaneous merkeliomatosis. Report of 2 cases]. 363 Mar 5

Depression is the most frequent psychiatric complication experienced by cancer patients. Recent surveys indicate that 17--25% of patients hospitalized with neoplastic disease suffer from depression severe enough to warrant psychiatric intervention. The disorder tends to be reactive in nature and occurs mot frequently among the severely ill. Despite an increased risk of suicide, self-destruction remains a rare occurrence in cancer victims. The most important etiologic factors are associated with the disease itself but additional factors have to do with its treatment. Those related to the illness include the psychological reaction to cancer, reaction to physical distress, central nervous system metastases, paraneoplastic syndromes, and metabolic disturbances. Factors related to the treatment include reaction to surgical procedures, radiation therapy, chemotherapy, and hormone therapy. Treatment for depression secondary to cancer should begin with careful assessment leading to identification of specific mechanisms and may include antidepressant drugs, psychotherapy, and a variety of adjunctive techniques. Little research has been done in this area, and most of it suffers from the use of inadequate diagnostic criteria. Controlled trials of available pharmacologic and nonpharmacologic treatments are urgently needed.
 ...
PMID:Depression secondary to cancer. 698 47

Genetic changes found in human osteogenic sarcoma cells, including loss of the p53 and Rb tumor suppressor elements and overexpression of the cyclin G1 (CYCG1) proto-oncogene, suggest the potential of gene transfer as a treatment for metastatic disease. In this study, we examined the effects of antisense cyclin G1, in comparison with antisense cyclin D1 (CYCD1) and enforced expression of the universal cyclin-dependent kinase inhibitor p21WAF1/CIP1 on the proliferation of human MG-63 osteosarcoma cells. Retroviral vectors bearing antisense CYCG1 as well as antisense CYCD1 and WAF1/CIP1 (in sense orientation) driven by the Moloney murine leukemia virus long terminal repeat promoter inhibited the growth and/or survival of transduced MG-63 cells in 2-7 day cultures. This represents the first demonstration that cyclin G1 is essential for the survival and/or growth of human osteosarcoma cells. Cytostatic and cytopathic effects were accompanied by a significant increase in the incidence of apoptosis, as determined by immunocytochemical analysis of DNA fragmentation. Furthermore, transduction of MG-63 cells with a retroviral vector bearing the suicide gene, herpes simplex thymidine kinase (HStk), induced cell death on treatment with ganciclovir, exhibiting pronounced bystander effects. Taken together, the data affirm the feasibility of modulating inducible cell cycle control enzymes as a potential gene therapy approach in the clinical management of osteogenic sarcoma.
 ...
PMID:Retroviral vector-mediated gene transfer of antisense cyclin G1 (CYCG1) inhibits proliferation of human osteogenic sarcoma cells. 758 20

One of the reasons for the development of cancers and their relentless malignant progression--even in the face of highly toxic anticancer therapies--is an enhanced ability to bypass mechanisms responsible for precipitating cell death. The latter include active cell death mechanisms often referred to as programmed cell death or apoptosis. Active cell death is a genetically controlled, intrinsic suicide process, and evidence is rapidly accumulating that cancers are more resistant to undergoing apoptosis than normal cells. This may be a major factor explaining the ability of small numbers of tumor cells, e.g. tumor emboli, to survive transit in the bloodstream and form distant metastases in ectopic organ sites. In addition, because many therapeutic agents ultimately kill tumor cells by inducing apoptosis, acquisition of an apoptosis-resistant phenotype could be a generic mechanism of drug or radiation resistance in cancer patients. It follows that uncovering the basis of the enhanced survival capacity of tumor cells is fundamental to gaining a better understanding of tumor progression, metastasis formation, and response to therapy. In this respect many of the principles thought to regulate apoptosis in cancers have been established using conventional, two-dimensional monolayer cell cultures of 'liquid' tumors, i.e. unicellular model systems. Suppression of apoptosis in solid tumors, however, may be governed by different cellular and genetic mechanisms. Evidence is presented in support of this hypothesis, and that multicellular architecture may render individual tumor cells within solid tumors less susceptible to apoptosis. This multicellular resistance--which may represent a form of group protection--can also be induced or acquired during cytotoxic drug chemotherapy or cytokine-mediated growth inhibition of solid tumors. It follows that disruption of solid tumor multicellularity may provide a means of enhancing the therapeutic destruction of small solid tumors such as occult micrometastases. Such disruptions may be brought about by a variety of so-called antiadhesive agents.
Invasion Metastasis
PMID:Impact of multicellular resistance on the survival of solid tumors, including micrometastases. 765 32

Obstetrician-gynecologists reviewed patient records of women delivering during January 1986-December 1992 to determine the maternal mortality rate and trends and the causes of maternal deaths in the maternity ward at the National University of Singapore. There were 26,173 deliveries and 9 maternal deaths (a maternal mortality rate of 22.9/100,000). The causes of maternal deaths were pulmonary embolism (underlying condition, systemic lupus erythematosus [SLE]), hemorrhage from multiple sites (thrombotic thrombocytopenia), acute exacerbation of SLE with interstitial pneumonitis, pulmonary fibrosis (systemic sclerosis), fulminant hepatitis (prior hepatitis and liver disease), and cerebral embolism (rheumatic heart disease with mitral valve replacement). There were also three incidental maternal deaths bringing the maternal mortality rate up to 34.4/1000. The incidental causes of death included septicemia from perforated peptic ulcer (uncontrolled thyrotoxicosis), multiple metastases from lung cancer, and suicide (family dispute over adoption of newborn). A cesarean section preceded 4 (44%) of the 9 maternal deaths. Two of these deaths were incidental maternal deaths. Cesarean section was related to two of the remaining six (33%) deaths. These findings show that traditional direct causes of maternal death (hemorrhage, sepsis, embolism, or hypertension) were not responsible for the maternal deaths at this tertiary facility. Instead, the women tended to have medical conditions that placed them at high risk of death regardless of pregnancy status.
 ...
PMID:Maternal mortality: evolving trends. 781 Nov 98

The effectiveness of combination therapy using a suicide gene and cytokine genes for the treatment of metastatic colon carcinoma in the mouse liver was investigated. Pre-established hepatic tumors treated with a recombinant adenoviral vector containing the herpes simplex virus thymidine kinase gene(tk) exhibited substantial regression, although all treated animals suffered from subsequent relapses. Although cotreatment with a mouse interleukin 2 (mIL-2)-containing adenoviral vector induced an effective antitumor immune response, the immunity waned with time, and the treated animals eventually succumbed to hepatic tumor relapse or distant metastases. In this study, mouse granulocyte macrophage colony-stimulating factor (mGM-CSF) gene was tested for its ability to further enhance and prolong the antitumoral cellular immunity. A fraction of the animals treated with tk + mIL-2 + mGM-CSF developed long-term antitumor immunity and survived for more than 4 months without recurrence. This long-term antitumor immunity could be enhanced further by subsequent "vaccination" with mIL-2-expressing parental tumor cells. The results indicate that local expression of GM-CSF in the hepatic tumors and prolonged mIL-2 expression are necessary to generate persistent antitumor immunity that is essential for the prevention of tumor recurrence and long-term animal survival.
 ...
PMID:Combination suicide and cytokine gene therapy for hepatic metastases of colon carcinoma: sustained antitumor immunity prolongs animal survival. 870 21

This protocol presents a new therapeutic approach to the treatment of patients with otherwise incurable malignant metastatic melanoma. Its objective is to define the safety of escalating doses of an anti-cancer treatment involving intratumoral injections of cells that produce recombinant retroviruses. The experimental treatment is based on the introduction into tumoral cells of a suicide gene coding for the herpes simple virus type 1 thymidine kinase (HSV1-TK). Cells that express HSV1-TK become sensitive to ganciclovir (GCV). GCV has no toxicity for normal cells, but kills cells expressing the HSV1-TK enzyme. Such toxicity is restricted to cells undergoing division. Introduction of the gene into tumoral cells is obtained through the intratumoral injection of murine fibroblasts modified by genetic engineering (M11 cells). These cells continuously produce recombinant defective retroviruses containing the HSV1-TK gene. Retroviruses can integrate their genes only when the cells they infect are undergoing division. Thus, after intratumoral injection of M11 cells, the tumoral cells, but not the quiescent cells of the healthy tissue surrounding them, express the HSV1-TK gene and can be destroyed by GCV. In addition, tumoral cells that do not express the gene, but which are located in the immediate vicinity of the transduced cells, are also destroyed through a "bystander effect," also restricted to cells undergoing division. It is therefore not necessary for all the tumoral cells to express HSV1-TK for all of them to be destroyed. Finally, preliminary data suggest that this localized tumoricidal activity may trigger a more general antineoplastic action, by facilitating a specific antitumoral immune response. The efficacy of the above therapeutic approach has been evidenced with animals in the treatment of brain tumors, of colic adenocarcinoma hepatic metastases and of malignant melanoma. A therapeutic trial on recurrent brain tumors or metastases has begun in the USA, using a similar approach. We propose a phase I-II clinical study of the treatment of metastatic malignant melanoma. The patients enrolled in the study must present a metastatic malignant melanoma that is no longer treatable by conventional therapy (life expectancy of patients < 12 months). Progressively increased doses of M11 cells (1 x 10(8), 2 x 10(8), 3 x 10(8) cells/cm3 of tumor) will be injected transcutaneously in the cutaneous, sub-cutaneous or ganglionary tumoral nodules. For a given dosage, four patients receiving the treatment will be studied. Four additional patients will be enrolled at the higher tolerated dosage. We will study the safety and the tumoricidal effect of the direct intratumoral injection of M11 cells followed by treatment with GCV at a constant, intravenous dosage of 10 mg/kg/d x 14 days.
 ...
PMID:Gene therapy for metastatic malignant melanoma: evaluation of tolerance to intratumoral injection of cells producing recombinant retroviruses carrying the herpes simplex virus type 1 thymidine kinase gene, to be followed by ganciclovir administration. 878 75

Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma.
 ...
PMID:Adenovirus-mediated interleukin-12 gene therapy for metastatic colon carcinoma. 887 30


1 2 3 4 5 6 7 8 Next >>