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

Antitumor effect of recombinant human tumor necrosis factor (TNF)-alpha lacking one to three amino acids from the N terminal part (TNFNv3) was tested for its antitumor effect on subcutaneous fibrosarcoma SA-1 tumors. Peritumoral treatment with 5 x 10(4) U TNFNv3 three times every second day significantly delayed tumor growth. Treatment with 10 times higher dose (5 x 10(5) U) produced 6.0 +/- 1.0 days tumor growth delay, but had side effects such as weight loss. The two new desmuramyl N-acyl dipeptides, LK-409 and LK-410, also exhibited such effect; however, the tumor growth delay was barely significant. The treatment was performed with two concentrations (2.5 micrograms and 25.0 micrograms) applied intraperitoneally for 5 consecutive days, without a dose-dependent effect. Combined treatment with TNFNv3 and desmuramyl dipeptides augmented the antitumor effect of treatments. The effect was additive and significant in the combination of 2.5 micrograms LK-410 with 5 x 10(5) U TNFNv3. LK-410 treatment also reduced the side effects of TNFNv3. The results indicate that combined treatment with both biological response modifiers is effective in tumor treatment.
 ...
PMID:Antitumor effect of recombinant human tumor necrosis factor-alpha analog combined with desmuramyl dipeptides LK-409 or LK-410 on sarcoma in mice. 147 73

Electrotherapy with direct current (DC) was performed on two murine tumor models, fibrosarcoma SA-1 and melanoma B16. Three Pt/Ir cathodes were inserted directly into the subcutaneous tumors and two anodes subcutaneously in the vicinity of the tumor. Significant tumor growth delay was achieved after electrotherapy and was dependent on DC intensity (0.6, 1.0, 1.4 and 1.8 mA). Melanoma B16 tumors were more sensitive to electrotherapy than SA-1 tumors. In order to enhance the antitumor effect of electrotherapy, combined treatment with interleukin-2 (IL-2) was performed. When both therapies were combined significant tumor growth delay and also higher curability rate was achieved. The results imply that electrotherapy can be an effective antitumor therapy and that the effects can be enhanced with additional IL-2 therapy.
 ...
PMID:Anti-tumor effect of electrotherapy alone or in combination with interleukin-2 in mice with sarcoma and melanoma tumors. 152 6

Intraperitoneal injection of human rIL-1 in a dose of 0.5 microgram daily for 5 d, or 1 microgram daily for 3 d, was capable of causing complete regression of immunogenic SA1 sarcoma growing subcutaneously in syngeneic or semisyngeneic mice. Higher doses of IL-1 were not more therapeutic against the SA1 sarcoma, but needed to be given to cause complete regression of the immunogenic L5178Y lymphoma. On the other hand, the P815 mastocytoma was much less responsive to IL-1 therapy, in that it failed to undergo complete regression in response to doses of IL-1 capable of causing regression of the L5178Y lymphoma. IL-1 caused regression of the SA1 sarcoma when given on days 6-8 of tumor growth, but not when given on days 1-3. This refractoriness of a small tumor to IL-1 therapy suggests that the antitumor action of IL-1 is based on an underlying host-immune response that is not generated until after day 3 of tumor growth. Direct evidence for the participation of host immunity in IL-1-induced tumor regression was supplied by results showing that IL-1 was not therapeutic against the SA1 sarcoma growing in T cell-deficient (TXB) mice, unless these mice were first infused with Ly-2+ and L3T4+ T cells from donor mice bearing an established SA1 sarcoma. In contrast, normal T cells, or T cells from donor mice bearing a YAC-1 lymphoma, failed to provide TXB recipients with the ability to cause regression of their SA-1 sarcoma in response to IL-1 treatment. The results are in keeping with the interpretation that exogenous IL-1, by augmenting the production of tumor-sensitized T cells, converts a subtherapeutic level of host immunity to a therapeutic level. The results suggest, in addition, that IL-1 only stimulates the replication of T cells that are already engaged in the antitumor immune response.
 ...
PMID:Interleukin 1-induced, T cell-mediated regression of immunogenic murine tumors. Requirement for an adequate level of already acquired host concomitant immunity. 314 99

The host cellular response to i.p. growth of the SA-1 spindle cell sarcoma was studied in semisyngeneic AB6F1 hybrid mice. At progressive stages of tumor growth mice were sacrificed, their ascites were collected, and changes in the numbers of tumor cells, macrophages, lymphocytes, and granulocytes were determined. It was found that macrophages were the predominant host cell that accumulated locally in response to tumor growth. Cytoxan treatment caused a 90% reduction in tumor cells without affecting the accumulation of macrophages. Six days after treatment with cytoxan, macrophages exceeded all other cell types present in the peritoneal cavity and outnumbered tumor cells by 20:1. However, in spite of this macrophage dominance, the tumor cells ultimately regrew to kill the host. Ascites tumors could be completely regressed, however, by following cytoxan treatment with an appropriately timed intratumor injection of endotoxin. The relatively long delay before endotoxin caused the tumor to regress suggests that endotoxin acted by stimulating the generation of anti-tumor immunity, rather than by directly augmenting the tumoricidal activity of macrophages.
 ...
PMID:Macrophage accumulation in murine ascites tumors. I. Cytoxan-induced dominance of macrophages over tumor cells and the anti-tumor effect of endotoxin. 677 24

One of the ways to increase drug delivery into cells and tissues is by a local application of short, intense electric pulses, i.e., electropermeabilization. This approach is used in electrochemotherapy to potentiate antitumor effectiveness of chemotherapeutic drugs. To determine whether electropermeabilization can potentiate antitumor effectiveness of cis-diamminedichloroplatinum(II) (CDDP), electrochemotherapy with CDDP was tested in vitro and in vivo on s.c. SA-1, EAT, and melanoma B16 tumors in mice. Electric pulses were applied to the tumors by percutaneously placed electrodes after i.v. injection of CDDP. Severalfold potentiation of CDDP antitumor effectiveness with electric pulses was obtained, inducing partial or complete responses in tumor growth. Electrochemotherapy was CDDP dose dependent, as well as dependent upon the amplitude of electric pulses. Also important was the sequencing and the interval of CDDP administration, relative to application of electric pulses. Specifically, a good antitumor effect without side effects was obtained with eight electric pulses (electric pulse amplitude, 1040 V; repetition frequency, 1 Hz; pulse width, 100 microseconds; electrode distance, 8 mm; 1300 V/cm) applied 3 min after i.v. injection of 4 mg/kg CDDP. With a higher CDDP dose (8 mg/kg), some long-term complete responses were obtained (14%) on melanoma B16 tumors. Thus, electrochemotherapy with CDDP offers an approach to making chemotherapy with CDDP more effective.
 ...
PMID:Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. 761 85

Experiments were undertaken to determine whether the depletion of CD4+ T cells from mice bearing an advanced immunogenic SA-1 sarcoma would result in an enhanced ability of interleukin-2 (IL-2) to cause tumor regression. The results show that whereas IL-2 therapy given as a 5-day course starting on day 10 of tumor growth caused complete regression of the tumor, it failed to cause regression if started on day 15 of tumor growth. However, in mice depleted of CD4+ T cells by treatment with anti-CD4 monoclonal antibody (mAb), IL-2 therapy started on day 15 resulted in appreciable tumor regression in most animals, and the therapeutic effect was greatly increased if two consecutive courses of anti-CD4 mAb and IL-2 therapy were given. On the other hand, treatment with anti-CD4 mAb alone had no effect on tumor growth. It was shown that the therapeutic action of combination therapy with anti-CD4 mAb and IL-2 was mediated by CD8+ T cells, because the therapeutic effect was completely ablated in mice depleted of CD8+ T cells with anti-CD8 mAb. Taken together these results suggest that, at a late stage of growth of an immunogenic tumor, depletion of CD4+ T cells can enhance the antitumor effect of IL-2 therapy by releasing CD(8+)-T-cell-mediated immunity from T-cell-mediated suppression.
 ...
PMID:Elimination of CD4+ T cells in mice bearing an advanced sarcoma augments the antitumor action of interleukin-2. 790 89

Anti-tumor effectiveness of tumor necrosis factor (TNF)-alpha applied peritumorally was assessed in combination with local electrotherapy on subcutaneous SA-1 tumors in mice. TNF and electrotherapy each induced significant tumor growth delay. In combined treatment using TNF and electrotherapy, a synergistic anti-tumor effect was observed, regardless of whether TNF was injected before or after electrotherapy. An extra anti-tumor effect was achieved when TNF in the same total dose (2 x 10(5) U) was split into a priming dose (0.5 x 10(5) U) 1 h before electrotherapy and the other (1.5 x 10(5) U) 24 h thereafter. As the result of this therapeutic combination survival rate of the animals was 40%. No animal survived more than 50 days in groups subjected to TNF or electrotherapy treatment alone. Combined treatment with TNF and electrotherapy induced massive tumor destruction, confirmed by histological examination 2 days after the treatment. The results indicate that TNF and electrotherapy interact and that they can be effective in control of local tumor growth.
 ...
PMID:Anti-tumor effect of tumor necrosis factor combined with electrotherapy on mouse sarcoma. 818 33

Two new TNF-alpha analogs were prepared and tested for their anti-tumor activity on fibrosarcoma SA-1 tumor model in vivo. In analog LK-801 two histidines (His107His108) were introduced into the surface loop thus enabling efficient purification by metal-affinity chromatography. This analog showed less side effects and can serve as a lead compound to look for other useful mutations. Another analog LK-802 was designed by introduction of additional pair of mutations (Cys95Cys148) into LK-801 in order to prepare disulfide linked TNF trimers. Cytotoxicity on mouse cell line L929 was comparable to TNF-alpha, but effect on tumor growth was quite reduced. Pharmacokinetic study revealed that serum levels of LK-802 were quite low in comparison to native TNF-alpha. This at least partially explains why anti-tumor activity of LK-802 is reduced and also illustrates the problems in designing the analogs with desired in vivo biological properties.
 ...
PMID:Searching for new TNF-alpha analogs having potential application in cancer therapy. 873 50

The aim of our study was to evaluate feasibility and therapeutic potential of electrogene therapy with p53 alone or combined with electrochemotherapy using cisplatin on two murine sarcomas with different p53 status. Antitumor effectiveness of three consecutive electrogene treatments with p53 was more effective in wild-type LPB tumors than mutated SA-1 tumors, resulting in 21.4% of tumor cures in LPB tumors and 12.5% in SA-1 tumors. Pretreatment of tumors with electrogene therapy with p53 enhanced chemosensitivity of both tumor models treated by electrochemotherapy with cisplatin. After only one application of this treatment combination in the LPB tumor model, specific tumor growth delay was prolonged in the combined treatment group compared to electrogene therapy with p53 or electrochemotherapy with cisplatin alone, whereas in SA-1 tumors this treatment combination resulted in 31.6% of cured animals. Results of our study show that electrogene therapy with p53 alone or combined with electrochemotherapy is feasible and effective treatment of tumors. The combination of electrogene therapy and electrochemotherapy after only one application resulted in complete regression of tumors.
 ...
PMID:Electrogene therapy with p53 of murine sarcomas alone or combined with electrochemotherapy using cisplatin. 1723 16

BACKGROUND.: Electrochemotherapy provides good local tumor control but requires adjuvant treatment for increased local response and action on distant metastasis. In relation to this, intramuscular interleukin-12 (IL-12) gene electro-transfer, which provides systemic shedding of IL-12, was combined with local electrochemotherapy with cisplatin. Furthermore, the dependence on tumor immunogenicity and immunocompetence of the host on combined treatment response was evaluated. MATERIALS AND METHODS.: Sensitivity of SA-1 sarcoma and TS/A carcinoma cells to electrochemotherapy with cisplatin was tested in vitro. In vivo, intratumoral electrochemotherapy with cisplatin (day 1) was combined with a single (day 0) or multiple (days 0, 2, 4) intramuscular murine IL-12 (mIL-12) gene electrotransfer. The antitumor effectiveness of combined treatment was evaluated on immunogenic murine SA-1 sarcoma in A/J mice and moderately immunogenic murine TS/A carcinoma, in immunocompetent BALB/c and immunodeficient SCID mice. RESULTS.: Electrochemotherapy in vitro resulted in a similar IC(50) values for both sarcoma and carcinoma cell lines. However, in vivo electrochemotherapy was more effective in the treatment of sarcoma, the more immunogenic of the tumors, resulting in a higher log cell kill, longer specific tumor growth delay, and also 17% tumor cures compared to carcinoma where no tumor cures were observed. Adjuvant intramuscular mIL-12 gene electrotransfer increased the log cell kill in both tumor models, potentiating the specific tumor growth delay by a factor of 1.8-2 and increasing tumor cure rate by approximately 20%. In sarcoma tumors, the potentiation of the response by intramuscular mIL-12 gene electrotransfer was dose-dependent and also resulted in a faster onset of tumor cures. Comparison of the carcinoma response to the combined treatment modality in immunocompetent and immunodeficient mice demonstrated that the immune system is needed both for increased cell kill and for attaining tumor cures. CONCLUSIONS.: Based on the comparison of the antitumor effectiveness of electrochemotherapy to intratumoral cisplatin administration, we can conclude that the fraction of cells killed and the tumor cure rate are higher in immunogenic sarcoma tumor compared to moderately immunogenic carcinoma tumor. The tumor cell kill and cure rate depend on the immune response elicited by the destroyed tumor cells, which might depend on the tumor immunogenicity. The effect of adjuvant intramuscular mIL-12 gene electrotransfer is dependent on the amount of IL-12 in the system and the immune competence of the host, as demonstrated by the dose-dependent increase in the cure rate of SA-1 tumors after multiple intramuscular mIL-12 gene electrotransfer and in the differential cure rate of TS/A tumors growing in immunocompetent and immunodeficient mice.
 ...
PMID:Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicity. 2341 58


1 2 Next >>