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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A marked and progressive decrease in the activity of the histamine forming enzyme, histidine decarboxylase (HDC), of tumors was found to be associated with the progressive growth of SV-40 virus induced and transplanted syngeneic non-metastasizing fibrosarcomas in inbred LSH Syrian hamsters. Histamine forming enzyme activity was highest in the smallest tumors (p < .005) and in the tumors with the slowest growth rate (p < .005, r - 0.84). Tumor histamine forming enzyme activity was highest for each interval of animal exposure to inoculated tumor cells in those animals which had limited their tumor growth to the smallest tumor size. These findings suggested a local anti-inflammatory effect of progressive tumor growth. Induced local inflammation by repeated intratumor injections of bradykinin markedly elevated tumor histamine forming enzyme activity above expected levels for tumors of the same size in a small group of individual animals which were sampled at random from a larger group of animals which were being studied for the tumor growth kinetics effects of repeated intralesional injections of bradykinin. Tumor histamine forming enzyme activity was highest in those animals which were managed by the frequency of injection and dose schedules which were found in the tumor growth kinetics study to be most effective in limiting tumor growth. These findings suggested that the observed anti-inflammatory effects of progressive tumor growth may be reversed by locally induced inflammation at the tumor site with beneficial effects on tumor growth.
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PMID:Decreases in histamine forming enzyme activity of non-metastasizing fibrosarcomas in hamsters with progressive tumor growth. 68 84

Oral daily administration of aspirin or indomethacin retarded growth of experimental tumors in mouse. Aspirin treatment, 150 mg/kg twice daily, inhibited growth of a transplantable mast-cell ascites tumor (P815) by 39-43% (p less than 0.001) and of a s.c. transplanted Lewis lung carcinoma by 52% (p less than 0.025) without adversely affecting body growth. The total serotonin, histamine and histidine decarboxylase content of the ascites tumor was also reduced as was the urinary excretion of the amines. Treatment with 3 and 5 mg/kg indomethacin resulted in 40% (p less than 0.01) and 80% (p less than 0.001) reduction, respectively, in ascites tumor growth. With the higher dose of indomethacin, no tumor was observed in half of the animals inoculated with tumor, although signs of indomethacin toxicity (reduced body growth, gastric lesion) was evident in the animals.
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PMID:Alteration of tumor growth by aspirin and indomethacin: studies with two transplantable tumors in mouse. 95 14

Repeated intratumor injections of SV-40 virus-induced and transplaned syngenic fibrosarcomsa in hamsters with bradykinin (BK) has produced markded slowing of tumor growth in comparison with control saline injections. Growth slowing was greatest when the injections were daily, with a decrease in growth slowing as injections became less frequent. The growth slowing also was dose dependent (greater with 250 mug BK injections than with 50 mug BK injections). BK-injected tumors, on histological study, were found to have marked infiltration with mononuclear cells. This was not encountered in noninjected or saline-injected tumors. Significant mononuclear cell infiltration of noninjected tumors was found in two tumor animals which had had one tumor injectecd with BK. Splenic histidine decarboxylase (HDC) activity was higher in BK tumor-injected animals than in saline tumor-injected animals. Splenic HDC activity was higher when studed nearer the period of daily intratumor injections. The findings of this study suggest a potential role of inportance for inter-related vasoactive substances which act as mediators of inflammation in the study and therapy of neoplasia.
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PMID:Accumulation of mononuclear cells in tumors with growth slowing and elevation in host splenic histidine decarboxylase activity following repeated tumor injections with bradykinin. 115 62

The present study suggests that newly synthesized histamine is involved in the development of some animal tumors (e.g., Lewis lung carcinoma in mice and Morris hepatoma in rats). A marked induction of histidine decarboxylase (HDC) and an increase in the histamine concentration were observed in the tumors approximately 1 week after inoculation, and there were parallel increases in ornithine decarboxylase activity and the concentrations of polyamines. The H2 receptor antagonist, cimetidine, significantly reduced tumor growth in the animal models while the H1 receptor antagonist, dexchlorpheniramine, had no effect, suggesting that histamine could act via H2 receptor sites. Extensive depletion of tumor histamine induced by local injection of Compound 48/80 did not result in a significant cytostatic effect. Monofluoromethylhistidine (MFMH), an enzyme-activated irreversible inhibitor of HDC, retarded the growth of hepatoma tissue culture cells grown in culture, and when infused s.c. at 60 mg/kg/day it greatly inhibited the development of tumors induced i.m. by hepatoma tissue culture cells in Buffalo rats. MFMH also had pronounced antitumoral effects on EMT6 sarcomas and Lewis lung carcinomas in mice, which were associated with inhibition of HDC and depletion of the histamine content of the tumors. These cytostatic effects were clearly enhanced when MFMH was combined in therapy with the specific ornithine decarboxylase inhibitor, DL-alpha-difluoromethylornithine. The antitumoral effects of the combination were associated with marked decreases in the tumor histamine and putrescine contents. It is proposed that nascent histamine, like newly synthesized putrescine and spermidine, plays a role in the rapid proliferation of animal tumors. Inhibition of HDC by essentially nontoxic drugs such as MFMH could represent a novel approach to the control of neoplastic growth.
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PMID:Involvement of histamine in growth of mouse and rat tumors: antitumoral properties of monofluoromethylhistidine, an enzyme-activated irreversible inhibitor of histidine decarboxylase. 669 68

Biogenic amines play an important role in regulating cell proliferation in the normal and neoplastic colon. Elevated histidine decarboxylase (HDC) activity has been measured in human colorectal tumors. H2 antagonists can suppress the growth of colorectal cancer and their inclusion in human therapy has been proposed. We studied the effects of histamine, cimetidine, mepyramine and alpha-fluoromethylhistidine (FMH) on the growth of colorectal tumors in ten patients in the 6-day mouse subrenal capsule assay (SRCA). The effect of the Hic antagonist DPPE was tested in two assays. In summary, a reduction of tumor size was achieved with histamine and DPPE. In addition, significant inhibition of tumor growth was seen in the FMH-treated animals. When pooled by their growth potential, as assessed by the growth of saline-treated controls, FMH and DPPE caused distinct tumor reduction in rapidly growing tumors. In the moderately growing tumors, histamine and mepyramine were the most effective.
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PMID:Effects of histamine, H1, H2 and Hic receptor antagonists and alpha-fluoromethylhistidine on the growth of human colorectal cancer in the subrenal capsule assay. 797 95

To evaluate the immunomodulatory effects of histamine in vivo, we analyzed an experimental syngenic tumor model using a colon adenocarcinoma cell line, CT-26, in Balb/c mice. In this model, distinct tumor growth was observed around 6 days after inoculation. Daily administration of cimetidine (0.12 mg/kg/day) significantly suppressed the increases in tumor volume and weight. On day 6 and day 7, histidine decarboxylase (HDC) activity was markedly increased. To examine the alterations in the local immune system, the cytokine expressions in the tumor tissue were measured by ribonuclease protection assay. The cytokine expression levels such as lymphotoxin-beta, tumor necrosis factor-alpha, interferon-gamma, interleukin-10, and interleukin-15 were considerably lower in tissues on day 14 than those on day 6. These decreased expressions were all restored by cimetidine. These results indicated that the effects of cimetidine on tumor growth in this model might be mediated by restoration of the decreased local cytokine expression, which exerts antitumoral effects.
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PMID:Effect of cimetidine on intratumoral cytokine expression in an experimental tumor. 1124 50

Histamine is a classical, but still interesting inflammatory mediator. Many people have long believed that histamine is derived from mast cells or basophils alone. However, the histamine-forming enzyme, histidine decarboxylase (HDC), is induced in a variety of tissues in response (i) to gram-positive and gram-negative bacterial components (lipopolysaccharides, peptidoglycan, and enterotoxin A) and (ii) to various cytokines (IL-1, IL-3, IL-12, IL-18, TNF, G-CSF, and GM-CSF). HDC is induced even in mast-cell-deficient mice. The histamine newly formed via the induction of HDC is released immediately and may be involved in a variety of immune responses. Reviewing our work and that of Schayer and Kahlson, the pioneers in this field, lead us to the conclusion that nowadays we need to understand that histamine can be produced via the induction of HDC by a mechanism coupled with the cytokine network. We call this histamine "neohistamine", to distinguish it from the classical histamine derived from mast cells or basophils. Neohistamine is involved in physiological reactions, inflammation, immune responses and a variety of diseases such as periodontitis, muscle fatigue (or temporomandibular disorders), stress- or drug-induced gastric ulcers, rheumatoid arthritis, complications in diabetes, hepatitis, allograft rejection, allergic reactions, tumor growth, and inflammatory side effects of aminobisphosphonates.
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PMID:[Induction of histidine decarboxylase in inflammation and immune responses]. 1149 27

Accumulating evidence indicates that histamine is involved in the modulation of cytokine expression patterns. We previously reported that daily treatment with the H(2) receptor antagonist, cimetidine, suppressed tumor growth through alteration of the local cytokine expression pattern. In this study, we used a mouse strain genetically lacking histidine decarboxylase (HDC), to evaluate the role of endogenous histamine synthesis on cytokine expression and tumor development. In the mutant mice, cimetidine had no effect on tumor growth, whereas an H(2) agonist, dimaprit, significantly enhanced tumor growth. When the HDC-deficient mice were implanted with mutant CT-26 cells stably expressing HDC, drastic suppression of tumor growth by cimetidine was observed, which was accompanied by augmentation of mRNA expression of LT-beta, TNF-alpha, and IFN-gamma in the tumor tissues. These results suggest that endogenous histamine synthesis in tumor tissues suppresses local tumor immunity via the H(2) receptors, resulting in tumor growth promotion.
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PMID:Histamine H(2) receptor-mediated modulation of local cytokine expression in a mouse experimental tumor model. 1237 15

In the present study, the impact of acquired neoplastic L-histidine decarboxylase (HDC) expression, and its direct consequence, the release of histamine in the tumor environment, was assessed on melanoma tumor progression. B16-F10 mouse melanoma cells were manipulated via stable transfection, and nine novel transgenic variants were generated in triplicates, constitutively expressing the full-length sense mouse HDC mRNA, a mock control, and an antisense HDC RNA segment, respectively. Establishing both primary skin tumors and lung metastases in C57BL/6 mice, the nine variants with different histamine-releasing capacities were subjected to a comprehensive comparative progression profiling in vivo. Our analyses showed trends of markedly accelerated tumor growth (P < 0.001), and moderately increased metastatic colony-forming potential (P = 0.010) along with rising levels of local histamine production. Using RNase protection assay for screening of the melanoma progression profile, and Western blotting for subsequent result validation, we looked for molecular progression markers affected by melanoma histamine secretion. Investigation of 21 functionally clustered markers associated with tumor proliferation, angiogenesis, invasivity, metastasis formation, local or systemic immunomodulation, and histamine signaling revealed positive correlations between histamine production, tumor histamine H2 receptor and rho-C expression (P < 0.001, P = 0.002, respectively). These observations confirm the involvement of histamine in the molecular machinery of melanoma progression.
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PMID:Phenotypic profiling of engineered mouse melanomas with manipulated histamine production identifies histamine H2 receptor and rho-C as histamine-regulated melanoma progression markers. 1589 39

The purpose of the present study was to investigate the influence of lack of histamine (HA) on tumor growth and functions of T cells in order further to illustrate the mechanism of immunological tolerance induction by HA. We assessed the phenotype and cytokine production of splenic lymphocytes in syngeneic HA-free (histidine decarboxylase knock-out) (HDC KO) and wild-type mice, inoculated subcutaneously with the LM2 murine breast cancer cell line. Relative quantification of target mRNA was performed with a TaqMan real-time RT-PCR assay. The CD4(+)CD25(high+) Treg cell numbers were significantly smaller in the tumor-bearing KO mice than in the wild type ones measured by flow-cytometry. The expression of forkhead box P3 (Foxp3) decreased significantly and the copies of splenic Tbox-21 (T-bet) transcriptional factor mRNA was higher in HDC KO tumor-bearing mice than those of normal mice. The cytokine levels showed that a smaller number of interleukin-13-producing Th2 cells were elicited compared to interferon-gamma-producing Th1 cells in the tumor-bearing HDC KO mice. In conclusion, the present study demonstrates that endogenous histamine stimulates the growth of breast adenocarcinoma tumor implants in mice by suppressing anti-tumor immunity.
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PMID:Impact of systemic histamine deficiency on the crosstalk between mammary adenocarcinoma and T cells. 1789 89


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