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)

Congenitally athymic (nude) and hereditarily asplenic (Dh/+) mice were painted with dimethylbenzanthracene (DMBA) to compare skin tumor development in these immunodeficient animals with their immunologically normal littermate controls. Papillomas were induced in all groups of mice. However, nude and Dh/+ mice were significantly more resistant than their normal littermates to tumor induction. Furthermore, the number of papillomas/mouse and the total tumor incidence were significantly greater in control mice and the latency period for tumor appearance was shorter and the tumor growth rate greater in normal mice compared to their immunodeficient littermates. Finally, nu/+ skin transplanted to nude mice and then painted with DMBA behaved in similar fashion as nude skin. These findings, when discussed in terms of target organs for DMBA, suggest a major role for the immune system in stimulating papilloma induction.
 ...
PMID:DMBA induced papillomas in congenitally athymic (nude) and hereditarily asplenic (Dh/+) mice: contrasts and comparisons with immunologically intact littermates. 9 36

In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor.
 ...
PMID:Evaluation of BCG administered by scarification for immunotherapy of metastatic hepatocarcinoma in the guinea pig. 18 11

A model for metastatic skin cancer using intradermal injection of Walker 256 carcinosarcoma has been developed in the rat. Using this model, antitumor activity of topically applied doxorubicin and diaziquone in Vanicream, Plastibase, and dimethyl sulfoxide (DMSO) as vehicles was compared with intraperitoneal injection of the drugs at the same doses beginning 4 days after injection of tumor cells. Doxorubicin applied topically at 0.5 mg/day for 4 days in Vanicream or Plastibase exhibited no antitumor activity, while i.p. administered doxorubicin at 0.5 mg/day for 4 days inhibited tumor growth at day 20 by 66%. Diaziquone applied topically at 0.1 mg/day for 4 days in Vanicream, Plastibase, or DMSO inhibited tumor growth at day 20 by 66, 86, and 43%, respectively, and cured animals of the skin tumor at a dose of 0.5 mg/day. Diaziquone administered i.p. at 0.5 mg/day for 4 days was lethal to rats, and at 0.1 mg/day it produced 93% inhibition of tumor growth at day 20. Diaziquone applied topically at 0.1 mg/day for 4 days in Plastibase cured rats of advanced tumor when treatment was begun 12 days after injection of tumor cells. The area under the plasma radioactivity time curve over 5 h for a single 0.64-mg dose of topically applied [ring-14C]diaziquone in DMSO was 0.01% that of the same dose of [ring-14C]diaziquone administered i.p. in non-tumored rats. The decrease in WBC count following topical application of diaziquone at a dose of 0.1 mg/day for 4 days, compared to the same dose of diaziquone administered i.p., was 62% in Vanicream, 81% in Plastibase and 33% in DMSO. Topical diaziquone was non-toxic to normal skin in the rat and in the domestic pig. It is concluded that topical application of diaziquone offers a therapeutic advantage over systemic treatment for metastatic cancer of the skin.
 ...
PMID:Topical chemotherapy of intradermal Walker 256 carcinosarcoma with diaziquone and doxorubicin in the rat. 405 22

The polyphenolic fraction isolated from green tea (GTP) is a potent inhibitor of phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In this study, we assessed the effect of GTP on both stage I and stage II skin tumor promotion, and also analyzed the effect of duration of GTP treatment on skin tumor promotion in SENCAR mice. Topical application of GTP (6 mg/animal) concurrently with each application of either TPA (3.2 nmol) or mezerein (3.2 nmol) in stage I or stage II of the murine skin tumor promotion protocol, respectively, resulted in significant protection against skin papilloma formation in terms of both tumor multiplicity (42-50%) and tumor growth (43-54%). More profound and sustained protective effects of GTP were evident when it was applied continuously during both stage I and stage II of the skin tumor promotion protocol concurrently with TPA or mezerein treatments, respectively. Under this treatment regimen, compared to non-GTP-treated positive controls, GTP application showed 71%, 37% and 74% protection in terms of tumor multiplicity, tumor incidence and tumor growth, respectively. These data indicate that GTP inhibits both stage I and stage II of skin tumor promotion and that the inhibition of tumor promotion depends on the duration of GTP treatment.
 ...
PMID:Inhibition of both stage I and stage II skin tumor promotion in SENCAR mice by a polyphenolic fraction isolated from green tea: inhibition depends on the duration of polyphenol treatment. 826 39

Chronic UV irradiation of the skin not only causes skin cancer in humans but modifies immune responses generated within the epidermis, resulting in impaired immunity against a variety of infectious as well as noninfectious agents. In mice, tumors induced by chronic UV irradiation grow faster when transplanted into mice that are immunosuppressed by UV irradiation. To investigate epidermal cells (EC) in UV-irradiated skin that inhibit the induction of immunity against tumors, the murine UV-induced LK2 regresser tumor was used. This tumor grows initially in vivo and then spontaneously regresses. In vivo T-cell depletion was used to determine that regression of LK2 tumors in unirradiated mice was mediated mainly by CD8+ T lymphocytes, with minor involvement of CD4+ T cells. Immunization of mice with tumor antigen-pulsed EC prepared from unirradiated mice enhanced immunity against subsequent inoculation of LK2 tumors, augmenting regression of the LK2 tumor due to increased activation of both CD4+ and CD8+ T-cell subsets against the tumor. By contrast, immunization with EC prepared from UV-irradiated skin inhibited the induction of antitumor immunity, enhancing LK2 tumor growth. This was caused by the dendritic epidermal T cells that remained within this UV-irradiated EC preparation inhibiting activation of CD4+ T cells, without affecting CD8+ T cell function. Hence, during the development of murine UV-induced skin tumors, dendritic epidermal T cell inhibition of CD4+ T cell activation may enable this skin tumor to escape immune-mediated destruction.
 ...
PMID:Dendritic epidermal T cells in ultraviolet-irradiated skin enhance skin tumor growth by inhibiting CD4+ T-cell-mediated immunity. 865 5

Angiogenesis is a crucial process for tumor growth and metastasis regulated by the balance of positive and negative factors. Vascular endothelial growth factor (VEGF/VPF) is a specific mitogen for endothelial cells that has been shown to be overexpressed in a variety of tumors and other inflammatory diseases. To analyze the implication of VEGF/VPF during tumorigenesis, we have studied its expression at different stages of tumor development using the mouse skin carcinogenesis model. VEGF/VPF mRNA was induced in skin in vivo after 12-O-tetradecanoylphorbol-13-acetate treatment. Constitutive up-regulation of VEGF/VPF at the mRNA and protein levels was also observed in premalignant papillomas and, at a higher level, in squamous carcinomas, suggesting a correlation between VEGF/VPF expression and tumor progression. A direct positive correlation between VEGF/VPF mRNA expression and the level of activated H-ras gene was found in a series of cell lines representing different stages of epidermal tumor development. Consequently, a clone of one of these cell lines, HaCa4, which has lost most of its v-ras expression, down-regulated VEGF mRNA expression concomitantly with its metastatic potential. Direct evidence of H-ras involvement in VEGF induction was obtained when an immortalized mouse keratinocyte cell line transduced with a retrovirus carrying v-H-ras showed highly increased VEGF/VPF mRNA levels. These data show that in mouse skin carcinogenesis, the VEGF/VPF angiogenic stimulus occurs early during premalignant papilloma development and further increases at later stages. Moreover, we demonstrate that increasing the activated H-ras dose, a phenomenon that takes place sequentially throughout mouse skin tumor development, may play an additional role by facilitating malignant in vivo progression through the modulation of VEGF/VPF-mediated angiogenesis.
 ...
PMID:Up-regulation of vascular endothelial growth factor/vascular permeability factor in mouse skin carcinogenesis correlates with malignant progression state and activated H-ras expression levels. 896 91

Keratoacanthoma is a common skin tumor characterized by rapid growth of a smooth dome-shaped nodule with a central plug of keratin, usually followed by spontaneous involution. We report the case of a giant keratoacanthoma on the face that continued to spread peripherally for several months despite vigorous therapeutic intervention. Treatment with methotrexate (25 mg intramuscularly) and Kenalog (triamcinolone acetonide, 40 mg intramuscularly) weekly finally slowed and stopped the expanding, deforming tumor growth and induced involution.
 ...
PMID:Aggressive giant keratoacanthoma of the face treated with intramuscular methotrexate and triamcinolone acetonide. 921 92

Nicotinamide (NA), a naturally occurring vitamin and a protease inhibitor, has been shown to be effective in treating some skin ailments. It inhibits cell proliferation and induces cell differentiation. This report shows the effects of NA on mouse skin tumor development and on the critical events involved in this process. NA reduced tumor growth, inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase activity, but induced the transglutaminase activity which was inhibited by TPA under different experimental conditions. The effects of NA on ornithine decarboxylase (ODC) and transglutaminase (TG) indicated that nicotinamide (NA) probably programmed the cells for their death in the natural course of time, i.e. programmed cell death. This observation indicates that NA might be a better agent for the detailed study and for the better use in prevention of cancer alone or in combination with other drugs.
 ...
PMID:Effects of nicotinamide on mouse skin tumor development and its mode of action. 1067 81

Merkel cell carcinoma was first described in 1972 by Toker and is an aggressive neuroendocrine skin tumor with a high metastatic potential. Merkel cell carcinoma is thought to derive from the neuroendocrine (Merkel) cells of the skin, although in contrast to fetal and especially adult Merkel cells, Merkel cell carcinomas express high levels of the Bcl-2 oncoprotein. Bcl-2 is capable of blocking programmed cell death and has been shown to play an important role in normal cell turnover, tumor biology, and chemoresistance. High Bcl-2 expression leading to prolonged survival of cells may therefore be of importance in the biological and clinical characteristics of Merkel cell carcinoma. In a SCID mouse xenotransplantation model for human Merkel cell carcinoma, we investigated the influence of the bcl-2 antisense oligonucleotide G3139 (Genta) on tumor growth in comparison with control oligonucleotides or cisplatin. Bcl-2 antisense treatment, targeting the first six codons of the bcl-2 mRNA, resulted in either a dramatic reduction of tumor growth or complete remission, whereas reverse sequence and two-base mismatch control oligonucleotides or cisplatin had no significant antitumor effects compared with saline-treated controls. Apoptosis was enhanced 2.4-fold in the bcl-2 antisense treated tumors compared with the saline-treated group, and no other treatment showed a comparable increase in apoptosis. Our findings suggest that bcl-2 antisense treatment may be a novel approach to improve treatment outcome of human Merkel cell carcinoma.
 ...
PMID:Bcl-2 antisense oligonucleotides (G3139) inhibit Merkel cell carcinoma growth in SCID mice. 1073 80

UV radiation causes a number of cellular changes within the skin which play a role in tumor outgrowth, including immunosuppression and production of growth-enhancing cytokines. Both of these enable tumors to grow but their relative importance in carcinogenesis is poorly defined. In this study, C3H/HeN mice were exposed to a single inflammatory dose of 410 mJ/cm(2) UVB radiation (plus 100 mJ/cm(2) UVA radiation) followed by the inoculation of a regressor squamous cell carcinoma into or the painting of oxazolone onto the treated skin. Tumors transplanted 2 or 3 but not 4 days after irradiation had a significantly higher growth rate than tumors inoculated into unirradiated control mice. In contrast, mice failed to respond to hapten when it was applied 2, 3 or 4 days after irradiation. Cytofluorimetric analysis demonstrated that the number of F4/80(+) Langerhans cells was not significantly reduced until 4 days after irradiation, while the number of dendritic epidermal T cells was significantly lower at all time points observed after UV-irradiation. Furthermore, a large cellular infiltration of CD11b(+), Gr-1(+), CD45(+) MHC class II(+) and CD45(+) MHC class II(-) cells into the epidermis was observed 2 and 3 days after irradiation, which corresponded with the enhanced tumor growth. To a lesser extent tumor growth was also associated with CD45(+) MHC class II(hi) cells, possibly the previously described UV-induced macrophage. In contrast, suppression of contact hypersensitivity corresponded with the reduction in dendritic epidermal T cells but not with other cell changes. The results suggest that, in this model, where immunosuppression did not appear to be responsible for enhanced tumor growth, inflammatory infiltrates may contribute to the promotion of skin tumor growth within UV-irradiated skin.
 ...
PMID:Enhanced tumor growth in UV-irradiated skin is associated with an influx of inflammatory cells into the epidermis. 1102 36


1 2 3 4 5 6 Next >>