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)

In 16 patients with 21 metastatic brain tumors and 9 patients with a malignant glioma, tumor volume, volume of the edematous tissue, edema production, speed of edema propagation and edema resolution were examined by using the CT. Edema production was determined according to a technique described previously and ranged between 0.09 and 1.63 ml/h in metastases and between 0.42 and 3.49 ml/h in gliomas. The speed of edema propagation ranged from 0.2-2.2 mm/h. Edema resolution can take place within the tissue (i.e. reabsorption into blood) as well by drainage into the ventricular or subarachnoid CSF. In a few small metastases with a small perifocal edema (without contact to the ventricule or the subarachnoid space) the amount of edema resolution within the tissue could be determined and averaged 0.0086 ml/h/cm3. This probably represents the reabsorption of edema fluid into capillaries within the edematous tissue. If this value is used to calculate the edema reabsorption in larger tumors, the resulting data are considerable lower than the respective edema production rate of that tumor. This indicates, that in larger tumors the main fraction of the edema fluid is draining into the ventricular and/or subarachnoid CSF.
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PMID:Formation and resolution of human peritumoral brain edema. 797 93

Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m2) plus cyclophosphamide (CTX)(600 mg/m2) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cancer. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metastatic disease: they received eight courses unless progression or unacceptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses (PR), nine stable disease, two progressive disease. Among the 25 evaluable patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confirmed complete response. 18 patients (72%) had a tumour reduction to 0-2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable patients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fever occurred in only 7% of the courses. A clinical congestive heart failure occurred in 1 patient following a total Epi dose of 960 mg/m2 and a bilateral quadrantectomy and radiotherapy. We conclude that (1) high-dose Epi + CTX is a very active regimen, in particular for the patients with locally advanced breast cancer; (2) breast conservation after this regimen in some of these patients may be considered; (3) neutropenia is the dose-limiting toxicity. Currently, a phase II study using the same combination given every 2 weeks together with r-methuG-CSF is ongoing.
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PMID:Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. 799 14

A case of the female patient with gastric carcinoma with metastases into lymph nodes and vertebrae is presented. Generalized DIC with subarachnoid haemorrhage confirmed by CSF examination has occurred in the course of the disease. Applied treatment failed.
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PMID:[Neurologic complications of disseminated intravascular coagulation in a patient with a stomach neoplasm]. 800 52

Metastatic or locally advanced renal cell carcinoma is refractory to chemotherapy and radiotherapy. Surgical treatment is the mainstay of treatment in these cases. The concept of surgical treatment of renal cell carcinoma was discussed by classifying the procedures into four categories: 1) radical nephrectomy; 2) nephron sparing surgery, such as partial nephrectomy and enucleation for small renal cancer detected incidentally by ultrasonography and CT; 3) extended surgery for cases having IVC tumor thrombus or with invasion of neighboring organs; and 4) surgery for metastatic disease. New therapies such as LAK, alpha-Interferon and IL-2 do not improve the 20% response rate. Gene therapy using appropriate vectors for introduction of IL-2. Interferon or GM-CSF genes to renal cancer cells is still at an experimental stage.
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PMID:[Surgical treatment for renal cell carcinoma]. 806 Jan 29

Therapeutic models using gene transfer into tumor cells have pursued three objectives: (1) to induce rejection of the tumor transduced with therapeutic genes, (2) to induce immune-mediated regression of metastatic disease, and (3) to induce long-lasting immunity to protect against challenge with tumor cells or clinical regrowth of micrometastatic disease. Because in vivo therapy for patients with cancer using gene transfer would, as a first step, attempt to eliminate the existing tumor, we have investigated whether antitumor immunity induced by tumor cells secreting a single cytokine could be increased by cotransfer of a second cytokine gene. To test this approach, CMS-5, a murine fibrosarcoma, was transduced with retroviral vectors carrying interleukin-2 (IL-2), interferon-gamma (IFN-gamma), or granulocyte-macrophage-colony-stimulating factor (GM-CSF) cDNA alone or IL-2 cDNA in combination with IFN-gamma or GM-CSF cDNA. Single cytokine-secreting clones were selected to match levels of cytokine production by double cytokine-secreting clones so that similar amounts of cytokine were secreted. IFN-gamma- and IL-2/IFN-gamma-secreting CMS-5 cells showed increased levels of major histocompatability complex class I expression compared with IL-2- and GM-CSF-secreting or parental CMS-5 cells, IL-2/IFN-gamma-secreting CMS-5 cells were always rejected by syngeneic mice, whereas the same number of CMS-5 cells secreting only one of these cytokines or mixtures of single cytokine-secreting CMS-5 cells were not rejected. In vivo depletion of CD4+, CD8+, or natural-killer effector cell subpopulations showed that CD8+ cytotoxic T cells were primarily responsible for rejection of IL-2/IFN-gamma-transduced tumor cells. Our data show the successful use of a single retroviral vector to stably transduce two cytokine genes into the same tumor cell, leading to an increased effect on the in vivo induction of antitumor immunity.
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PMID:Augmentation of antitumor immunity by tumor cells transduced with a retroviral vector carrying the interleukin-2 and interferon-gamma cDNAs. 811 32

More than 80% of malignant gliomas have been reported to recur locally after conventional chemoradiation therapy. This regional pattern of recurrence has encouraged the introduction of new treatments for local tumors. Since 1987 interstitial brachytherapy using Iridium-192 seeds has been carried out in our department for malignant brain tumors. The present study was designed to evaluate the patterns of recurrence following interstitial brachytherapy and to assess how this recurrence differs from that observed in patients treated by conventional means. Ten patients who satisfied the following criteria were selected among 41 patients treated with brachytherapy. The criteria were; 1) histologically diagnosed to be malignant glioma (astrocytoma grade III or glioblastoma), 2) followed up with MRI every month after the brachytherapy, 3) follow-up period was more than 6 months, and 4) the time of recurrence was confirmed. The patients were classified into 3 groups according to the patterns of tumor recurrence as follows; 1. Local recurrence group: The tumor recurred near the pretreatment tumor site. 2. Necrotomy group: Reoperation was performed because of neurological deterioration and radiographic evidence of increasing mass effect with surrounding edema. Neurological symptoms were unchanged or improving during the 6 months after the reoperation. 3. CSF seeding group: Primary tumor was well controlled, but seeding via cerebrospinal fluid was recognized on MRI. Local recurrence occurred in three patients, necrotomy was carried out in three patients, and CSF metastases were defined by both MRI and clinical symptoms in four patients. Median radiation does was 33 Gy in the local recurrence group, 57.6 Gy in the necrotomy group, and 43.2Gy in the CSF seeding group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Patterns of recurrence in malignant gliomas after brachytherapy]. 816 95

Expression of an extended panel of cytokine genes was investigated by reverse polymerase chain reaction (PCR) in 10 freshly excised melanoma metastases infiltrated by lymphocytes (TIL). cDNA encoding for CD3-delta and tyrosinase could be amplified in all samples, confirming the presence of T lymphocytes and melanoma cells. Cytokine genes possibly transcribed by both cell types, such as GM-CSF, IL-6 and IL-10 could be amplified from 5, 2 and 2 samples respectively. In contrast, IL-1 beta and TNF-alpha mRNA were never detectable, IL-1 alpha, IL-3 and IL-7 mRNA could be observed only in one case each. Transcripts encoding for TGF-beta 1 were observed in 8 samples, while TGF-beta 2 and 3 mRNA were detectable in only 2 specimens. mRNA encoding for cytokine genes typically transcribed by antigen-stimulated T lymphocytes, such as IL-2, IL-4 and IFN-gamma were rarely or never detectable (none, none and 1 of the samples respectively). In one case, where no cytokine gene transcription was detectable at the time of surgery, we addressed the question of the antigenicity of the tumor and of the functional competence of TIL. A primary tumor cell line was generated and cultured TIL were induced to transcribe IL-2 and IFN-gamma genes by incubation with the autologous irradiated tumor cell line, but not with autologous EBV-transformed cells. In these conditions, tumor-specific cytotoxic T lymphocytes (CTL) could be generated only after 3 weekly re-stimulations. In contrast, if autologous irradiated EBV-transformed cells were added to the cultures, specific CTL could be detected after one single tumor stimulation. Thus, signs of active responsiveness in terms of lymphokine gene mRNA are seldom detectable in melanoma metastases. Tumor-specific responses, however, including IL-2 and IFN-gamma gene expression and generation of CTL can be produced in vitro from specimens in which no cytokine gene mRNA is detectable ex vivo.
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PMID:The pattern of cytokine gene expression in freshly excised human metastatic melanoma suggests a state of reversible anergy of tumor-infiltrating lymphocytes. 818 65

Murine I-A+ epidermal antigen-presenting cells (APCs) have been shown to be capable of presenting soluble tumor fragments (TFs), as a source of tumor-associated antigens (TAAs), for primary and secondary tumor immune responses. In this study we investigated whether incubation of epidermal APCs in interferon-gamma (IFN-gamma) modulates their ability to present TAA and whether the effects of IFN-gamma on the presentation of tumor antigen correspond to its effects on alloantigen presentation in both primed and unprimed systems. Our results show that three weekly subcutaneous injections of naive mice with GM-CSF-cultured but not with fresh TAA-pulsed epidermal APCs induce protective tumor immunity in naive mice and that the immunostimulatory effect of GM-CSF in this system is abrogated by coculture of epidermal cells in IFN-gamma. Furthermore, epidermal APCs are able to present TAA to primed, tumor-immune mice, as assessed by the elicitation of tumor-specific delayed-type hypersensitivity after injection of TAA-pulsed epidermal APCs. IFN-gamma was found to inhibit tumor antigen presentation by freshly prepared epidermal APCs in this system. The effects of IFN-gamma on the presentation of tumor antigen correlated well with its effects on the primary and secondary mixed epidermal cell-lymphocyte reaction, indicating that IFN-gamma differentially modulates the function of epidermal APCs with regard to induction versus elicitation of immunity.
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PMID:Interferon-gamma inhibits tumor antigen presentation by epidermal antigen-presenting cells. 819 94

The production of cytokines by tumor cells has been suggested as the molecular perturbation responsible for the development of malignant tumors. The behavior of tumor cells in animals is presumed to be affected by these factors, which include such hematopoietic cytokines as GM-CSF, IL-1, and IL-6. Here, we report findings demonstrating that GM-CSF is produced by many murine transplantable tumors with metastatic ability in the lungs, and IL-6 and/or IL-1 are produced by the tumors metastatic in the liver. We discuss the notion that the particular organ or organs in which tumor cells metastasize may be associated with the type of cytokines produced by the tumors. Metastatic spread requires interactions of tumor cells with components of the extracellular matrix of host tissues or with other cells, almost all of which depend on cell surface determinants such as cell adhesion molecules. We also discuss the possibility that the expression and adhesive potentials of adhesive protein (CD44) may be regulated by the cytokine (GM-CSF) excreted from the tumor cells. We then emphasize the possibility that both gene expression of cytokines and adhesive proteins play a critical role in tumor metastasis and in determining organ specificity in metastasis.
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PMID:[The roles of cytokine in organ-specific tumor metastasis]. 834 46

Twenty-two women affected by metastatic breast carcinoma have been treated with a combination of levo folinic acid 100 mg/m2 plus 5-fluorouracil 450 mg/m2 i.v. on day 1-2, and epidoxorubicin 75-90 mg/m2 on day 2. This treatment cycle was repeated every 21-28 days. No patients had previously received chemotherapy for metastatic disease. Fourteen patients (64%) showed a major objective response with 3 complete (14%) and 11 partial responses (50%). Three patients showed a stabilization of disease and 5 (23%) progressed. All patients received ondansetron as antiemetic treatment which led to complete protection from vomiting in 68% of cases. Grade 1-2 diarrhea was recorded in 27% of the patients. Ten patients received recombinant human granulocyte-colony stimulating factor (rhG-CSF) as leukopenia-preventive treatment. In this group of patients the interval between chemotherapeutic cycles was shorter than in the group of 12 patients who did not receive rhG-CSF.
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PMID:Levo folinic acid and 5-fluorouracil plus high dose epidoxorubicin as first line treatment for metastatic breast carcinoma. 838 92


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