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Results for “tumor development”

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PubMed1999

Cyclin D1 overexpression in mouse epidermis increases cyclin-dependent kinase activity and cell proliferation in vivo but does not affect skin tumor development.

In a previous study, we showed that synchronized proliferation of mouse epidermis was induced by topical application of 12-O-tetradecanoyl-phorbol 13-acetate. Here, we used this system to study modifications in the cell cycle regulation and kinetics of proliferation in transgenic mice that overexpress cyclin D1 (K5D1 mice). Overexpression of cyclin D1 corresponded with an increase of proliferation in the epidermis of these transgenic mice. After proliferation reached its peak, the labeling index remained high in the transgenics, but not in the wild-type animals. In addition, cyclin D1/cyclin-dependent kinase (CDK) complex formation increased in the transgenic mice and was correlated with elevated CDK4 and CDK6 kinase activities. However, the increased CDK activities were not sufficient to effect mouse skin tumor development. In summary, these results show that cyclin D1 has a unique growth-promoting role in tumor development, but does not act as an oncogene independent of ras activity.

Animals↗

PubMed2003

c-Jun regulates eyelid closure and skin tumor development through EGFR signaling.

To investigate the function of c-Jun during skin development and skin tumor formation, we conditionally inactivated c-jun in the epidermis. Mice lacking c-jun in keratinocytes (c-jun(Deltaep)) develop normal skin but express reduced levels of EGFR in the eyelids, leading to open eyes at birth, as observed in EGFR null mice. Primary keratinocytes from c-jun(Deltaep) mice proliferate poorly, show increased differentiation, and form prominent cortical actin bundles, most likely because of decreased expression of EGFR and its ligand HB-EGF. In the absence of c-Jun, tumor-prone K5-SOS-F transgenic mice develop smaller papillomas, with reduced expression of EGFR in basal keratinocytes. Thus, using three experimental systems, we show that EGFR and HB-EGF are regulated by c-Jun, which controls eyelid development, keratinocyte proliferation, and skin tumor formation.

Animals↗

PubMed2001

The methylenetetrahydrofolate reductase (MTHFR) gene in colorectal cancer: role in tumor development and significance of allelic loss in tumor progression.

BACKGROUND AND AIM: Folate deficiency predisposes to sporadic colorectal cancer (CRC). Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme and a polymorphism at position 677 (C677T), is associated with reduced enzyme activity. We investigated whether this functional polymorphism modulates the risk of developing CRC. METHODS: This was a retrospective case-control study. 136 unselected cases of sporadic CRC and 848 normal population controls were genotyped for the MTHFR C677T polymorphism. Tumor tissue was genotyped to assess loss of heterozygosity (LOH). RESULTS: MTHFR CT heterozygotes had a significantly increased risk of developing CRC (53.7% of CRC cases vs 38.4% of controls), odds ratio 1.86 (95% CI 1.3-2.7, p < 0.005). No increased cancer risk was observed in TT homozygotes. The MTHFR 'T' allele frequency was significantly higher in the cancer group (0.3713) as compared to controls (0.2900, p < 0.008). LOH at the MTHFR locus was observed in 18% of informative cancers, with exclusive loss of the variant 'T' allele, in all cases. CONCLUSION: In this study of a homogenous northern European population, MTHFR CT heterozygotes had an almost two-fold increased risk of developing sporadic CRC. The exclusive pattern of MTHFR allele loss in cases of LOH, suggest that functional MTHFR activity within a tumor might play an important role in the survival and progression of a colonic neoplasm.

Adenocarcinoma↗

PubMed1984

Serial transplantation to nude mice of an androgen-dependent pilosebaceous tumor developed in Suncus murinus.

The pilosebaceous tumor spontaneously developed on the sidegland of an old male Suncus murinus was serially transplanted into male nude athymic (BALB/c-nu/nu) mice. By the 18th generation, tumor growth occurred in about 70% of them. The transplantability of the tumor maintained in these male mice to female or castrated male nude mice was less than 35%. The histological features of the tumor did not differ by the hormonal status of hosts. Tumor growth started later and was slower in females than in males. This androgen dependency seems to be restricted to an initial period of growth, since the transplantability to males was decreased by castration within a week after grafting. The tumors grown in males possessed both cytoplasmic and nuclear androgen receptors and those in females cytoplasmic androgen receptor only. The latter tumors were found androgen-sensitive, because treatment with testosterone propionate significantly increased tumor size. In addition, after [3H]-testosterone administration, bound radioactivity was detected in the nuclear fraction from female as well as male hosts. Although the mechanism responsible for the development of these androgen-independent sensitive cells is unknown, the variance in transplantability to female hosts suggests that the original tumor was composed of androgen-dependent and androgen-independent cells.

Animals↗

PubMed1993

Failure of ozone and nitrogen dioxide to enhance lung tumor development in hamsters.

We tested the hypothesis that the two common oxidant air pollutants, ozone and nitrogen dioxide, modulate the development of respiratory tract tumors in Syrian golden hamsters. The animals received subcutaneous injections of the carcinogen diethylnitrosamine (20 mg/kg) twice a week while being exposed continuously to an atmosphere of 0.8 parts per million (ppm)* of ozone or 15 ppm of nitrogen dioxide. Animals were killed 16 weeks or 24 to 32 weeks after the beginning of the treatment. Ozone delayed the appearance of tracheal tumors and reduced the incidence of tumors in the lung periphery. A suspected neuroendocrine differentiation of those lung tumors could not be established by immunocytochemistry due to overfixation of tissues. On the other hand, ozone seemed to mitigate development of hepatotoxic lesions mediated by diethylnitrosamine. In animals treated with diethylnitrosamine and exposed to nitrogen dioxide, fewer tracheal tumors and no lung tumors were found. Only a few lung tumors were produced in animals treated with diethylnitrosamine and kept in an atmosphere of 65% oxygen. The previously observed neuroendocrine nature of tumors induced by simultaneous exposure to diethylnitrosamine and hyperoxia could not be established because the long fixation of tissues precluded immunocytochemical stains. Animals treated with diethylnitrosamine and kept in filtered air while being housed in wire-mesh cages developed fewer lung tumors than animals given the same treatment and kept on conventional bedding in shoebox cages. Although all inhalants tested are known to produce substantial cell proliferation in the respiratory tract, it was not possible to document whether this would enhance lung tumor development. The role of the two common air pollutants, ozone and nitrogen dioxide, as possible additional risks in the pathogenesis of lung cancer in animals continues to remain uncertain.

Animals↗

PubMed1986

Separation of early diffuse alveolar cell proliferation from enhanced tumor development in mouse lung.

A/J mice given urethan (1000 mg/kg) followed by four injections of butylated hydroxytoluene (BHT) (400 mg/kg) developed within 4 mo approximately 40% more lung tumors than mice treated with urethan and given four injections of corn oil. Administration of the metabolic inhibitor piperonyl butoxide prior to BHT injection abolished overall alveolar cell proliferation although it did not completely suppress type II alveolar cell proliferation. Tumor multiplicity in those animals remained significantly higher (29%) than in corresponding controls. In mice treated with 3-methylcholanthrene repeated injections of BHT (300 mg/kg) increased tumor multiplicity by a much larger factor (500-800). Pretreatment of mice with BHT reduced the number of tumors produced by methylcholanthrene and at the same time blocked all cell proliferation following additional injections of BHT; nevertheless, BHT treatment given after methylcholanthrene again increased tumor multiplicity by the same factor (500-800%) seen in animals not made tolerant to BHT. It is concluded that the enhancing effect of BHT on lung tumor development is not due to the production of diffuse alveolar cell hyperplasia.

Animals↗

PubMed2003

Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks.

The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of inorganic arsenics in human and experimental animals, was investigated in male Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided into three groups and received drinking water containing MMA(V) at doses of 0 (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences were found between the control and the MMA(V)-treated groups regarding clinical signs, mortality, hematological, and serum biochemistry findings. Quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci in liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)-treated group. In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium. A variety of tumors developed in rats of all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats and there were no significant differences among the groups. Thus, it could be concluded that, under the present experimental conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not cause tumor development in male F344 rats even after 2 years exposure.

Administration, Oral↗

PubMed1981

[Changes in resistance to tumor development in various strains of mice exposed to immunologic agents during the neonatal period].

In the course of exposures to the immunological agents (BCG, complete Freund's adjuvant) during the postnatal period, the resistance to tumor development induced with chemical carcinogens was found to increase in C57BL/6 mice, particularly in BALB/c and random-bred ones; meanwhile in C3H/He mice it declined. At the same time C3H/He mice showed a decrease in the resistance to the development of spontaneous tumors of the mammary glands. The changes recorded correlated with those seen in the immunocompetent organs.

Animals↗

PubMed1999

Renal oncocytoma: multifocality, bilateralism, metachronous tumor development and coexistent renal cell carcinoma.

PURPOSE: We analyzed a large series of cases of renal oncocytoma to define the incidence of coexistent renal cell carcinoma, multifocality, bilateralism and metachronous tumor development. MATERIALS AND METHODS: Between 1980 and 1997, 100 men and 38 women with a mean age of 68 years with oncocytoma, were treated surgically at our institution. We analyzed tumor characteristics and reviewed specimens for coexistent renal cell carcinoma. RESULTS: Tumors were discovered incidentally in 58% of the cases. Specimens were obtained from 84 radical and 70 partial nephrectomies. Tumor size ranged from 0.3 to 14.5 cm. (median 3.2). Oncocytoma was unilateral in 131 cases (95%) and bilateral in 7 (5%), while there were multiple oncocytomas in 8 (6%). Mean followup was 41 months (range 0 to 200). The disease specific survival rate was 100% and no patient had metastasis. In 6 patients (4%) metachronous oncocytoma developed during followup. No patient had locally recurrent oncocytoma after partial nephrectomy for a solitary renal oncocytoma. Renal cell carcinoma and oncocytoma were found in 14 patients (10%), including unilateral synchronous disease in 9 and bilateral synchronous disease in 5. CONCLUSIONS: Our data support the benign nature of renal oncocytoma. Multifocality, bilateralism and metachronous tumor develop in approximately 4 to 6% of all cases. Renal cell carcinoma coexisted in 10% of oncocytoma cases.

Adenoma, Oxyphilic↗

PubMed1997

Consequences of chromosomal abnormalities in tumor development.

This article highlights recent advances in the molecular structure and function of proteins that are activated or created by chromosomal abnormalities and discusses their possible role in tumor development. The molecular characterization of these proteins has revealed that tumor-specific fusion proteins are the consequence of most chromosome translocations associated with leukemias and solid tumors. An emerging common theme is that creation of these proteins disrupts the normal development of tumor-specific target cells by blocking apoptosis. These insights identify these chromosomal translocation-associated genes as potential targets for improved cancer therapies.

Animals↗

PubMed1993

Excess of multifocal tumors in nephroblastoma: implications for mechanisms of tumor development and genetic counseling.

Referring to the mutational theory of carcinogenesis in embryonal tumors, it is commonly accepted that patients with multifocal tumors are hereditary cases. This is based on the implicit assumption that each tumor results from a single mutational event occurring in a cell that has already inherited a mutation, and that these tumors are independent. We studied the distribution of tumors in 1,868 cases where the focality was known (SIOP 1, 2, 5 and 6). Using all the supposed gene carriers (bilateral and unilateral multifocal cases), and assuming a Poisson distribution of tumors, we estimated the mean number m of tumors in each kidney to be 0.37. Comparing the observed distribution of cases to the expected one, we found a very bad fit to this hypothesis (P < 10(-9)). This is due to an excess of multifocal tumors, particularly in unilateral cases. These findings have important implications in genetic counseling, since the usual practice of considering multifocal tumor patients as hereditary cases may result in a large overestimate of the recurrence risk in such cases. The implications for the mechanisms of tumor development are also discussed.

Chi-Square Distribution↗

PubMed1989

Modulation of lung tumor development in mice with the soybean-derived Bowman-Birk protease inhibitor.

Male strain A mice were treated with a single i.p. injection of 3-methylcholanthrene (MCA). Four months later, the number of lung tumors was counted. In mice treated three times a week, for 8 weeks, with crude soybean extract containing the Bowman-Birk protease inhibitor (BBI), the number of lung tumors was significantly lower than in control animals receiving carcinogen treatment only (40-70% of controls). On the other hand, treatment initiated 8 weeks after MCA only had no effect on tumor development. A reduction in the number of lung tumors was also found in animals treated i.p. or orally with purified BBI three times a week for 8 weeks following MCA administration. It is concluded that BBI is capable of partially blocking the development of lung tumors in mice.

Animals↗

PubMed1982

Sequential changes in tumor development induced by 1,4-dinitrosopiperazine in the nasal cavity of F344 rats.

Tumor development was examined sequentially in the nasal cavity of male F344 rats given 0.01% 1,4-dinitrosopiperazine (DNP) in their drinking water for various periods. Rats were sacrificed at 10-week intervals for up to Week 50. On continuous DNP administration, simple hyperplasia of the nasal cavity epithelium was observed from Week 10, papillary hyperplasia, nodular hyperplasia, and papilloma was observed from Week 20, and carcinoma was observed from Week 30. Carcinoma was observed in 100% of the animals given DNP for 50 weeks. The carcinomas were adenocarcinomas (86%), adenosquamous cell carcinomas (10%), and undifferentiated carcinomas (4%). Simple hyperplasia was distributed evenly in the nasal cavity. Seventy % of the nodular hyperplasias and 81% of the carcinomas were located in the ethmoturbinate and about 75% of the papillary hyperplasias and papillomas were located in the nasoturbinate and maxilloturbinate. These findings suggest that nodular hyperplasia is very important as a precursor of carcinoma in the nasal cavity of rats treated with DNP and that papilloma is less important in relation to carcinoma development.

Animals↗

PubMed1991

Inhibitory effect of streptozotocin on tumor development in transgenic mice bearing an elastase I-SV40 T-antigen fusion gene.

Transgenic mice, bearing a fusion gene of rat elastase I promoter and SV40 T-antigen, developed acinar cell tumors of the pancreas, as predicted by the model. In addition, they developed insulinomas and somatostatin (delta)-cell hyperplasia of the pancreatic islets. The insulinomas and the delta-cell hyperplasia appeared to be functional, as evidenced by changes in plasma glucose, insulin, and somatostatin. Streptozotocin, which has been shown to inhibit pancreatic carcinogenesis in the hamster model, significantly reduced the numbers of insulinomas and delta-cell hyperplasias. Streptozotocin did not cause a statistically significant reduction in exocrine tumors.

Animals↗

PubMed2006

Do MSI-L sporadic colorectal tumors develop through "mild mutator pathway"?

BACKGROUND: The mutator pathway implied in the development of colorectal cancer (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be subdivided according to the level of instability: MSI-H (high), MSI-L (low) or stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true biologic significance of MSI-L is still uncertain. The objective of this study was to further clarify if the MSI-L phenotype could reflect a distinct pathway of tumor development with a different clinical behavior. METHODS: We analyzed the clinicopathological and genetic variables of 156 patients with sporadic CRC in relation with the level of MSI of the tumors. RESULTS: We have found that MSI-L tumors are someway in the middle of MSI-H and MSS CRC, as they share some features with each of the other 2 subgroups: left side location, lower incidence of LOH at MSH2 as MSS and Dukes B (stage II TNM) like MSI-H. Moreover, MSI-L tumors show higher incidence of KRAS mutations. CONCLUSION: We believe that MSI-L tumors could be considered a distinct phenotype that develops through a "mild mutator pathway."

Aged↗

PubMed1998

Chromosomal abnormalities and tumor development: from genes to therapeutic mechanisms.

This article highlights the recent advances in our understanding of the molecular structure and function of proteins that are activated or created by chromosomal abnormalities and discusses their possible role in tumor development. The molecular characterization of these proteins has revealed that tumor-specific fusion proteins are the consequence of the majority of chromosomal translocations associated with leukemias and solid tumors. A common theme that emerges is that creation of these proteins disrupts the normal development of tumor-specific target cells by blocking apoptosis. These insights identify these chromosomal translocation-associated genes as potential targets for improved cancer therapies.

Apoptosis↗

PubMed2005

The role of macrophages in tumor development.

Macrophages constitute a large proportion of the immune cell infiltrate, which is present in many tumors. Activation state of macrophages is greatly influenced by their environment, leading to different macrophage subsets with diverse functions. Although previously regarded as potent immune cells that are capable of destroying tumor cells, recent literature focuses on the ability of macrophages to promote tumor development due to secretion of mediators, like growth and angiogenic factors. It is now becoming increasingly clear that a complicated synergistic relationship exists between macrophages and malignant cells whereby tumor cells can affect macrophage phenotype, and vice versa. As such, macrophages and their contribution in cancer development are currently subject of debate.

Animals↗

PubMed1993

[Malignant tumor developing in transplanted tissue in the oral cavity (case report)].

Primary and metastatic malignant tumors appears frequently in the head and neck region. The occurrence of malignancies in tissues--transplanted to this area--are extraordinary rare. Authors report about a case, where the tumor developed in a cylindroid jump flap, used to the closure of the cleft palate. They discuss theoretical aspects, as well as the course of the disease.

Adult↗