Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Ab1), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31, 44, 51, 71, 82 and 91) demonstrated specificity for the combining site of Ab1, and appeared to recognize 2 partly overlapping idiotopes on Ab1. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab1 (Ab1'), as shown by competitive Ab1-antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab1 binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-91-immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals.
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PMID:Vaccination with anti-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity. 805 52

The plasminogen activation system is considered to play an important role in cancer growth and metastasis. Both plasminogen activators (PAs) and their fast-acting inhibitors are produced in tumor cells and their surrounding tissues. In order to clarify the influence of the existence of malignant tumor in urinary tract on the systemic fibrinolytic activity, we designed a study in which we compared the plasma levels of PAs and their inhibitors between before and after radical resection of tumors. Fourteen patients with renal cell carcinoma and 14 patients with transitional cell carcinoma participated in the study. In both groups, plasma levels of tissue-type plasminogen activator and urokinase-type plasminogen activator before the operation were higher than those 15 days after operation. The plasma level of plasminogen activator inhibitor 1 (PAI-1), however, did not change after the operation in the renal cell carcinoma group, and it decreased slightly in the transitional cell carcinoma group although it was not significant. When these values of the groups with or without metastasis were compared to other organs or lymph nodes, the PAI-1 level before operation was significantly higher in the group with metastasis than that without metastasis. In the three groups divided by the degree of atypia, PAI-1 level in the most atypical group was the highest. These results suggest that the fibrinolytic system in the plasma of cancer patients may play an important role in tumor growth and metastasis.
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PMID:Plasminogen activators and plasminogen activator inhibitor 1 in urinary tract cancer. 814 Jun 79

High frequency loss of alleles and cytogenetic aberrations on the short arm of chromosome 3 have been documented in renal cell carcinoma (RCC). Potentially, three distinct regions on 3p could encode tumor suppressor genes involved in the genesis of this cancer. We report that the introduction of a centric fragment of 3p, encompassing 3p14-q11, into a highly malignant RCC cell line resulted in a dramatic suppression of tumor growth in athymic nude mice. Another defined deletion hybrid contained the region 3p12-q24 of the introduced human chromosome and failed to suppress tumorigenicity. These data functionally define a tumor suppressor locus, nonpapillary renal carcinoma-1 (NRC-1), within 3p14-p12, the most proximal region of high frequency allele loss in sporadic RCC as well as the region containing the translocation breakpoint in familial RCC. Furthermore, we provide functional evidence that NRC-1 controls the growth of RCC cells by inducing rapid cell death in vivo.
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PMID:A tumor suppressor locus within 3p14-p12 mediates rapid cell death of renal cell carcinoma in vivo. 815 56

Unfortunately the efficacy of the treatment of the metastatic or recurrent renal cell carcinoma (RCC) has not improved during the last few years. Recently effort has been put into the experimental and clinical evaluation of so-called "biological response modifiers" (BRM; cytokines and related peptides) as treatment modalities for RCC. The present results are, however, still disappointing. Since BRM, if applied alone, are largely ineffective as antineoplastic agents, more experimental studies are now necessary to test the antineoplastic value of their combinations, which seem to be more promising. In the present study, the in vivo effect of tumor necrosis factor a (TNF a) and/or interferon a (IFN a) on the macroscopic tumor growth (external caliper measurements of tumor size) and on the cell proliferation (in vivo 3H-thymidine labelling index, LI, and mitotic index, MI) of a human RCC xenograft line in nude mice has been investigated. Neither of these substances alone nor their combination was effective in changing the time course of the tumor sizes and the growth patterns of the treated tumors in a statistically significant manner as compared to the untreated controls. Also the cell kinetic parameters were only marginally affected by these treatments, whereby TNF a alone proved to be more effective than IFN a alone. However, compared to the effect of TNF alpha alone, the combination with IFN alpha leads to some amelioration of the cell kinetic perturbations and also to an appreciable shift in the growth patterns of the tumors from distinct Gompertzian (under TNF alpha alone) to near exponential (under the combination treatment; p < 0.05). As a consequence, the tumors grow more slowly under the combined treatment during the observation time, and on the other hand, their growth does not decelerate as much as under TNF alpha alone. Actually, if tumor growth continues in the same way, the extrapolation of the present data predicts smaller and greater tumors than the control tumors in the TNF alpha and in the combination treatment groups respectively. Notably, in the combination the effect of the IFN alpha seems to predominate. This is also seen in the effect of this combination on the cachexia of these tumor-bearing animals: either alone or in combination with TNF alpha, IFN alpha partially protects the animals from tumor-growth associated weight loss. Although the direct antineoplastic in vivo effect of the present cytokine combination against this human RCC xenograft line is rather limited, the potential antagonizing effect of IFN alpha on the development of cachexia should be further explored.
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PMID:Treatment with tumor necrosis factor alpha and interferon alpha of a human kidney cancer xenograft in nude mice: evidence for an anticachectic effect of interferon alpha. 816 54

Aryl pyrimidinones, including bropirimine, exert anti-tumor activity through the induction of interferon (IFN)-alpha. Herein, the direct anti-tumor effect of bropirimine on 17 renal cell carcinoma (RCC) surgically obtained was examined using an organ culture system closely resembling the in vivo state, and also using the heterotransplanted nude mouse system. The findings obtained using the organ culture system showed that bropirimine inhibited 3H-thymidine uptake significantly in 15 of the 17 RCC (88.2%) compared with the control. Furthermore, the 3H-thymidine uptake was dose-dependently inhibited in 3 of the 17 tumors (17.6%). The oral administration of bropirimine against RCC heterotransplanted in nude mice (JRC 901: an erythropoietin-producing strain) tended to inhibit tumor growth dose-dependently, but not significantly (mean tumor weight ratio: T/C ratio: over 43%, degeneration degree of tumor: incomplete). However, the production of erythropoietin from the JRC 901 was significantly inhibited. These findings suggest that bropirimine has a direct anti-tumor activity, without the mediation of IFN-alpha induction, against human renal cell carcinoma.
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PMID:A study on direct antitumor activity of bropirimine (oral interferon inducer) for renal cell carcinoma. 817 35

Antitumor effects of interleukin-2 entrapped in liposomes (IL-2 liposomes) on Renca, murine renal cell carcinoma of spontaneous origin, were evaluated by in vivo and in vitro experiments. As a local treatment model, IL-2 liposomes at a dose of 1.0 x 10(4) units were for 7 days injected adjacent to the Renca tumors inoculated in the back of BALB/c mice. The treatment inhibited the tumor growth and prolonged the survival time of mice significantly compared to the control (p < 0.01). Serum IL-2 levels after subcutaneous administration of IL-2 liposomes confirmed its slow releasing mechanism into blood circulation. The spleen cells from mice following the IL-2 liposome treatment showed higher cytotoxicity in vitro than that of IL-2 alone using Renca, YAC-1, and P-815 cells, which was determined by 51Cr-release assay. Indirect immunoperoxidase staining of tumor-infiltrating lymphocytes (TILs) showed that accumulation of Lyt-2+ and L3T4+ cells were seen in the tumor treated with IL-2 liposomes. These results indicate that IL-2 liposomes have a long-acting cytotoxicity against renal cell carcinoma caused by a slow release mechanism generated through the efficient local immune response mediated by TILs.
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PMID:Antitumor effect of interleukin-2 entrapped in liposomes on murine renal cell carcinoma. 818 79

The antiproliferative effect of laser-generated shock waves (L-SW) was investigated on a human renal cell carcinoma, RC-8, grown subcutaneously in the nu/nu mouse. The RC-8 is characterized by the syndrome of humoral hypercalcemia of malignancy (HHM) associated with profound cachexia, increase of serum Ca level, hypophosphatemia, and an enhancement of serum parathyroid-like peptides. In this model system, the effects on cachexia and tumor growth were studied after a series of pulses (3-200) generated by a Candela LFDL/3 equipped pulsed-dye laser with optical fiber guided through a hypodermic needle with a 45 degrees angle bended tip, stuck through the skin of the mouse, and positioned directly below the tumor. The antitumor effect, expressed as a delay of tumor growth, was found to be dependent on number of pulses applied, tumor size, and growth rate (alpha). Treatment of RC-8 with alpha = 0.21 was effective only after 200 pulses combined with a tumor volume smaller than 100 mm3. Under these conditions a growth delay of approximately 8 days was observed, paralleled by delay of animal weight loss (cachexia). Under conditions of a decreased growth rate of RC-8 (alpha = 0.13), the susceptibility toward L-SW was found to be increased, expressed by a suppression of tumor growth after 100 pulses. However, no L-SW-associated delay of cachexia was observed under these latter conditions.
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PMID:Tumor growth delay by laser-generated shock waves. 820 46

The effect of treating a human renal cell adenocarcinoma xenografted into Balb/c-nu/nu (nude) mice with recombinant human tumor necrosis factor alpha (TNF alpha) and the cytostatic agent etoposide (ETP) as monotherapy or combination has been studied. Antitumor effects were evaluated by determining growth of the tumor implants by external caliper measurements and tumor cell proliferation by determining the labelling index (LI) after pulse labelling with 3H-thymidine. The toxicity of the treatment with TNF alpha and/or ETP was also studied by measuring the animal weight. Monotherapy with TNF alpha had no effect on tumor growth or proliferation. Treatment with ETP as a single agent, TNF alpha plus ETP applied concurrently and TNF alpha plus ETP two days later led to a slight inhibition of tumor growth and also to a slight decrease of the LI. In contrast to a monotherapy with TNF alpha, all therapeutic modalities containing ETP showed an increased toxic effect on the animals represented by a distinct weight loss. This suggests that the minute efficacy of the treatment observed could well be due solely to its toxicity. In contrast to two other studies, no additive or synergistic effect of the antineoplastic activity of TNF alpha and/or ETP was found. The intertumoral variation of human renal cell carcinomas could be one reason for the different results with this therapeutic regimen.
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PMID:Treatment of a human renal cell carcinoma in nude mice with recombinant human tumor necrosis factor alpha and etoposide. 823 May 48

In this study, we evaluated 16 surgically treated cases of metastatic lung tumors originating from renal cell carcinoma. Ten males and 6 females with ages ranging from 31 years to 74 years (average 60.8 years) were examined. Five cases had solitary metastasis, 4 had ipsilateral multiple metastasis, and 7 had bilateral metastasis. The average number of lung metastatic legion was 3.3. Disease free intervals ranged from 0 to 120 months (average 22.6 months). Tumor doubling time calculated in only 8 cases, ranged from 36 to 510 days (average 126 days). In 8 cases, tumor doubling time could not be calculated because tumor growth was too slow. Partial resection or segmental resection was performed in 14 cases, 8 with ipsilateral and 6 with bilateral lung metastasis. Lobectomy was performed in only two cases. Five year survival rate was 43% as determined by the Kaplan-Meier method. We believe that such cases possessing a slow tumor growth rate have a better survival rate.
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PMID:[Surgical analysis for metastatic lung tumor originating from renal cell carcinoma]. 851 61

Interleukin-12 (IL-12) was found to be an active anti-tumor agent in 3 established murine solid tumors: B16 melanoma, Lewis lung carcinoma and renal cell carcinoma (RenCa). IL-12 was well tolerated over a 100-fold dose range. Only the high-dose treatment of IL-12 resulted in a clear reduction in the number of lung metastases from B16 melanoma and Lewis lung carcinoma. Treatment of animals bearing Lewis lung carcinoma with IL-12 in combination with fractionated radiation therapy was markedly dose-modifying, indicating that IL-12 was acting synergistically with radiation. Treatment of animals bearing the same tumor with monocyte colony-stimulating factor (M-CSF) along with fractionated radiation therapy resulted in a parallel increase in tumor growth delay with increasing dose of M-CSF, indicating that M-CSF was affecting a subpopulation of tumor cells in addition to those killed by radiation therapy. The combination of IL-12 with M-CSF was most effective with radiation therapy, especially in the clinically relevant dosages of 2 and 3 Gy per fraction. By isobologram analysis, IL-12 and M-CSF, along with fractionated radiation therapy, resulted in a greater-than-additive (synergistic) tumor response.
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PMID:In vivo studies with interleukin-12 alone and in combination with monocyte colony-stimulating factor and/or fractionated radiation treatment. 854 1


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