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)

We examined various prognostic factors of metastatic renal cell carcinoma. Patients who had metastasis at nephrectomy (A group, 38 cases) and those who had metastasis as recurrent tumors after nephrectomy (B group, 38 cases) entered in this study. Five-year survival rate of total cases after confirmation of metastatic foci was 15% and there was no statistical significant difference between A and B groups. Several pathological factors were related to poorer prognosis and included large diameters of original tumors, positive lymph nodes, higher grade tumors and non-clear cell type tumors. Patients who have a solitary lung metastasis showed better prognosis compared to those with multiple lung metastases or metastases of other organs. Two factors related to treatment were shown to contribute to better prognosis. These were the response to interferon alfa (IFN alpha) and the possibility of total resection of visible metastatic tumors. Patients who belong to A group were shown to achieve markedly better therapeutic benefit from IFN alpha or IFN alpha plus anticancer drugs. Five-year survival rate for the responders was 40%, as compared to less than 5% for the non-responders. Ten-year survival rate for patients with metastasis who had undergone complete resection of visible tumor was 50%, and the for patients belonging to B group Showed 80%. We concluded that these prognostic factors should be considered to decide how to select patients with metastatic renal cell cancer.
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PMID:[Prognostic factors for metastatic renal cell cancer]. 763 45

We investigated the usefullness and problems of arterial administration of lymphokine activated killer (LAK) cells in combination with systemic IL-2 in the treatment of metastatic renal cell carcinoma (RCC). Ten nephrectomized patients with extrapulmonary and/or nonresectable metastases were treated with arterial infusions of LAK cells and systemic rIL-2 (5 x 10(5) IU twice a day) for 1-12 weeks. Leukapheresis was carried out once or twice a week, and two LAK cell populations generated from two gravity subtypes of peripheral blood lymphocytes were administered separately. Five of 15 metastases treated showed appreciable regression of metastatic sites including bone, muscle and lymph nodes. Two of 15 showed a minor response. Local pain due to metastasis was relieved or disappeared in 6 patients. There was no correlation between the response of the patients and the number of LAK cells used. The 24- and 56-month survival rate was 50 and 25%, respectively. No serious side effects were experienced during treatment. We conclude that regional arterial administration of LAK cells in combination with a low dose of IL-2 is worthwhile as an alternative treatment modality to conventional therapy for a selected group of patients with advanced RCC.
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PMID:Treatment of advanced renal cell carcinoma using regional arterial administration of lymphokine-activated killer cells in combination with low doses of rIL-2. 764 36

Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-alpha, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-alpha at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-alpha was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreatment using rIL-2, rIL-2 and rIFN-alpha, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific to rIL-2.
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PMID:Low-dose interleukin-2 in combination with interferon-alpha effectively modulates biological response in vivo. 768 66

Recombinant interleukin-2 (IL-2) products (e.g. aldesleukin, teceleukin) are nonglycosylated, modified forms of the endogenous compound. IL-2 acts as a pleiotropic mediator within the immune system, having a variety of effects via specific cell surface receptors. The interaction of IL-2 with the IL-2 receptor induces proliferation and differentiation of a number of T lymphocyte subsets, and stimulates a cytokine cascade that includes various interleukins, interferons and tumour necrosis factors. Antitumour effects of IL-2 appear to be mediated by its effects on natural killer, lymphokine-activated killer (LAK) and other cytotoxic cells. In vivo and in vitro effects of IL-2 seem to be dependent to a large extent on the environment; many studies have reported conflicting results, perhaps due to diverse populations of effector cells, the availability of other cytokines that have synergistic or inhibitory influences, and the dosage regimens used. The recombinant products appear to be biologically indistinguishable from native IL-2 in vitro and in vivo; the former induce minor antibody formation but this does not appear to alter functional properties. In patients with metastatic renal cell carcinoma, IL-2 therapy achieves average objective response rates of 20% (range 0 to 40%), with a complete response rate of about 5% (range 0 to 19%). Response duration varies considerably but can be durable (lasting for > 12 months), with some patients remaining in complete response for > 60 months. It is unclear at present whether higher dosage regimens improve clinical response, or whether combination therapy with other agents and/or adoptive therapy is beneficial. Survival duration may depend on the risk factors present, with poorer performance status and more than one site of metastases associated with shorter survival times. Patients with metastatic malignant melanoma receiving IL-2 as monotherapy show an average objective response rate of 13% (range 3 to 24%); however, objective response rate averages 30% (range 4 to 59%) when IL-2 is used in combination with other agents. Overall median survival appears to be about 10 months. Preliminary data indicate that IL-2 produces a lower response rate in patients with refractory colorectal carcinoma, ovarian cancer, bladder cancer, acute myeloid leukemia or non-Hodgkin's lymphoma. Adverse effects accompanying high dose, intravenous IL-2 therapy can be severe, with cardiovascular, pulmonary, haematological, hepatic, neurological, endocrine, renal and/or dermatological complications frequently requiring doses to be withheld.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. 769 34

Advanced metastatic renal cell carcinoma has been shown to be responsive to immunotherapy but the response rate is still limited. We have investigated the therapeutic potential of systemic interleukin-4 (IL-4) administration for the treatment of pulmonary metastases in the murine Renca renal adenocarcinoma model. Renca cells were injected iv in Balb/c mice to induce multiple pulmonary tumor nodules. From Day 5, Renca-bearing mice were treated with two daily injections of recombinant murine IL-4 for 5 consecutive days. IL-4 treatment induced a significant reduction in the number of lung metastases in a dose-dependent manner and significantly augmented the survival of treated animals. Immunohistochemistry studies, performed on lung sections, showed macrophage and CD8+ T cell infiltration in the tumor nodules 1 day after the end of IL-4 treatment. The CD8 infiltration increased by Day 7 after IL-4 treatment. Granulocyte infiltration was not detectable. To clarify further the role of the immune system in IL-4 anti-tumor effect, mice were depleted of lymphocyte subpopulations by in vivo injections of specific antibodies prior to treatment with IL-4. Depletion of CD8+ T cells or AsGM1+ cells abrogated the effect of IL-4 on lung metastases, whereas depletion of CD4+ T cells had no impact. These data indicate that CD8+ T cells and AsGM1+ cells are involved in IL-4-induced regression of established renal cell carcinoma.
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PMID:Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model. 772 87

The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16 patients with metastatic renal cell carcinoma. In all patients s.c. rIL-2 resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours, as determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha serum concentrations remained elevated up to 24 hours following single s.c. administration of rIL-2. Total secondary TNF-alpha release, as assessed by the area under the curve (AUC), appeared to be independent of dose distribution of rIL-2 (10 million IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2 induced TNF-alpha release was significantly higher in patients who had received prior rIL-2 immunotherapy, while steroids resulted in a significant suppression of TNF-alpha release. Secondary TNF-alpha release was statistically associated with progression-free survival of renal cell carcinoma patients and may be a prognostic factor in patients receiving rIL-2.
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PMID:In vivo tumor necrosis factor-alpha as indicator of biologic and clinical response to low-dose SC recombinant interleukin 2. 773 21

Clear cell odontogenic tumor is a rare neoplasm of the jaws that histologically may be confused with metastatic renal cell carcinoma. A review of 17 cases revealed that these tumors are aggressive, with a tendency to recur locally after surgery; they also may metastasize both regionally and distantly. There is a marked female predilection, and most cases are discovered during the fifth to seventh decades of life. Seventy percent occur in the mandible, appearing as poorly marginated radiolucencies. We conclude that this tumor is malignant and should be referred to as clear cell odontogenic carcinoma; it requires an aggressive surgical approach.
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PMID:Clear cell odontogenic carcinoma. A clinicopathologic analysis. 777 24

Reduced expression of nm23 has been associated with increased metastases and decreased survival in a variety of malignancies. In the present study, the expression of nm23 was examined by Northern and Western blot analyses in a series of cell lines derived from patients with metastatic renal cell carcinoma. Two of twelve (17%) informative cell lines derived from 9 patients had loss of heterozygosity at Nm23-H1. Twenty-two renal cancer cell lines derived from primary tumors, 5 cell lines derived from metastatic tumors and 4 short-term cultures of normal proximal renal tubular cells all expressed Nm23 mRNA in varying amounts. On average, the level of expression of Nm23 mRNA in short-term cultures of benign proximal renal tubular cells was found to be similar to the level seen in renal cancer cell lines. Twenty-eight cell lines derived from renal primary tumors and 8 cell lines derived from metastatic tumors expressed both the Nm23-H1 and Nm23-H2 proteins. High or low relative expression of nm23 at the mRNA or protein level did not correlate with survival. The absence of any anomalous pattern of expression of the nm23 genes and the lack of correlation of expression with survival suggests that nm23 does not play a central role in the progression of this tumor type.
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PMID:Expression of nm23 in cell lines derived from patients with metastatic renal cell carcinoma. 777 45

In metastatic renal cell carcinoma, most conventional antineoplastic drugs have yielded no or little efficacy. To evaluate the tolerance and therapeutic efficacy of second line chemo/immunotherapies, we treated patients with advanced metastatic renal cell carcinoma upon progression after previous antineoplastic therapy employing an outpatient combination of subcutaneous (SC) recombinant interferon-alpha (rIFN-alpha) and intravenous (IV) 5-fluorouracil(5-FU). Thirty-three patients with metastatic renal cell carcinoma received SC doses thrice weekly of rIFN-alpha at 10 million U/m2 over 8 consecutive weeks. Additionally, patients received IV 5-FU at 750 mg/m2 in weeks 1-3 and 5-7; treatment cycles were repeated until disease progression. Of 33 patients, one achieved a complete remission (response duration, 24 months) and two patients presented with partial remissions (median response duration, 7 months) of pulmonary metastases upon rIFN-alpha/5-FU after failing SC recombinant interleukin-2 (rIL-2) and rIFN-alpha. The present chemo/immunotherapy regimen was overall well tolerated with low to moderate systemic toxicity and predominantly constitutional symptoms i.e., fever, chills, and malaise. In summary, the second line outpatient chemo/immunotherapy regimen of SC rIFN-alpha/IV 5-FU demonstrated a limited albeit significant efficacy in pretreated patients with progressive metastatic renal cell cancer.
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PMID:Interferon-alpha/5-fluorouracil: a novel outpatient chemo/immunotherapy for progressive metastatic renal cell carcinoma. 778 Apr 83

Although clear cell carcinomas have been described in numerous anatomic sites, their occurrence in the gallbladder and extrahepatic bile ducts (EHBD) is practically unknown. We report 10 such cases. Seven arose in the gallbladder and three in the EHBD; all patients with gallbladder tumors were females with cholelithiasis whose ages ranged from 56 to 68 years. Patients with EHBD tumors were younger (38 and 40 years of age) and had extrahepatic biliary obstruction and abdominal pain. Two patients with gallbladder carcinomas had elevated serum carcinoembryonic antigen (CEA) levels, and another without hepatic involvement had markedly elevated circulating levels of alpha-fetoprotein (AFP). Histologically, nine tumors were adenocarcinomas and one was a squamous cell carcinoma. Seven adenocarcinomas consisted of cords, sheets, nests, papillae, and trabeculae of clear cells with well-defined cytoplasmic borders. Two were composed predominantly of glands and papillary structures. The cells contained PAS-positive diastase-labile granules and were cytokeratin- and EMA-positive and immunoreactive for erythropoiesis-associated antigen. One gallbladder tumor contained areas of hepatoid differentiation, a feature described in gallbladder neoplasms only once before. These areas were AFP-positive and immunoreactive for CEA. By electron microscopy, they showed hepatoid differentiation with formation of bile canaliculi. In two gallbladder tumors, neoplastic cells contained subnuclear vacuoles reminiscent of early secretory endometrium. Foci of conventional adenocarcinoma or mucinous carcinoma were recognized in all nine tumors. The squamous cell carcinoma showed only foci of squamous differentiation with keratinization. The clear cells of this neoplasm had a trabecular and solid growth pattern. These clear cell neoplasms of the gallbladder and EHBD must be differentiated from metastatic renal cell carcinoma, based upon the presence of areas of conventional adenocarcinoma or foci of squamous differentiation since results of special stains and immunohistochemistry are similar in both neoplasms. One of the patients with EHBD carcinoma is alive and symptom-free 6 years following right hepatic lobectomy. Five patients with gallbladder tumors had direct extension into the liver and died with metastases. Two are living with metastases.
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PMID:Clear cell carcinomas of the gallbladder and extrahepatic bile ducts. 780 41


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