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)

Ten patients with large inoperable desmoid tumors in various body locations were treated with testolactone. Four tumors (40%) responded with major regressions, i.e., more than 50% reduction in volume. Eight patients received nonsteroid anti-inflammatory drugs (indomethacin, sulindac, or sulindac with warfarin and vitamin K1 [Mephyton]) for periods of 2 to 91 months. There was one major regression, one partial regression, and three instances of tumor growth arrest over periods up to 8 years. Seven patients were treated with nonsteroid anti-inflammatory drugs concurrent with or after testolactone or tamoxifen. There were five major regressions and one partial regression with extensive central necrosis of an enormous intra-abdominal tumor. The last patient has been treated for only 12 months, with no change in tumor volume. It appears that estrogens function as growth factors for desmoid tumors, and that minimization of these effects inhibits tumor growth in some, but not all, cases. In those instances where antiestrogens were not effective as single agents, the tumors usually responded to subsequent nonsteroid anti-inflammatory drug therapy. Withdrawal of estrogen may be followed by inhibition of transcription of genes that support tumor cell proliferation, and sulindac and indomethacin may augment these effects by inhibiting prostaglandin and cyclic AMP synthesis and the activity of protein kinase C. Warfarin may function as a protonophore to acidify the cytoplasm and prevent the alkalinization that is necessary to initiate DNA synthesis and cell cycle progression, again an impairment of the transcription process.
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PMID:Testolactone, sulindac, warfarin, and vitamin K1 for unresectable desmoid tumors. 203 59

Based on a detailed clinical and laboratory investigation of 89 patients with histologically verified desmoid tumor and the pertinent medical literature, we have reviewed the etiologic factors, clinical characteristics, and results of treatment of this rare disorder. The incidence of the tumor in the Finnish population is low, 2.4 to 4.3 new cases per 10(6) inhabitants per year. The age distribution profile demonstrated four distinct peak periods: the juvenile period, the fertile period, the middle-age period and the old-age period. The juvenile desmoid tumor is an extraabdominal tumor found in young girls, the fertile variety is an abdominal tumor found in women, the middle age variety is also overwhelmingly abdominal but the sex ratio approaches equality, whereas in the old age group, both abdominal and extraabdominal tumors are equally frequent and the sex ratio is equal. In all male patients, the growth rate was low. A low growth rate was also recorded in young girls. A growth rate of twice that speed was seen in fertile women and four times that speed in the middle age group. In the old age group, a low growth rate, equal to that of male patients, was a rule. The fertile female patients with desmoid tumor had a significant predisposition to estrogen dominance and deviation from progesterone dominance. The direct relationship of the growth rate to the level of endogenous estrogen in the female patients and the demonstration of significant amounts of estradiol but not progesterone receptors in the tumor cytosol further suggest that the growth rate of desmoid tumor is regulated by steroid sex hormones. A significant number of patients with an abdominal desmoid tumor had a history of surgical trauma in the region of subsequent tumor growth. A very high number of the patients demonstrated multiple minor malformations of the bony skeleton. An increased frequency of these malformations was also recorded in the families of the patients and the distribution of the malformations among the family members was compatible with an autosomally dominant pattern of inheritance. After operation, the frequency of recurrence was not statistically different, regardless of whether the tumor was completely removed or not. A combination of operation and radiotherapy did not reduce the frequency of recurrences; in fact, it doubled it.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The desmoid syndrome. New aspects in the cause, pathogenesis and treatment of the desmoid tumor. 394 57

Eighty histologically verified cases of the desmoid tumor (DT) have been analyzed with regard to factors possibly contributing to the etiology and/or growth behavior of this uncommon neoplasm. Considering the four statistical age components, the "fertile" female and "menopausal" varieties of the DT grew distinctly faster (0.1 less than P greater than 0.05 and less than 0.05), and the female "juvenile" variety distinctly slower (0.1 less than P greater than 0.05) than the male DTs. In a visual estimate, the fertile female patients had a significant (P less than 0.01) predisposition to estrogen predominance, while fewer patients than expected displayed progesterone predominance or were at balance (P = NS and less than 0.01, respectively). Thirty-two per cent of the patients with an abdominal DT had been previously operated in the region of subsequent tumor growth. Significantly more pregnancies were observed in patients with abdominal DT than with extra-abdominal DT (P less than 0.05). On only one occasion did sigmoideoscopy reveal colonic polyposis (Gardner's syndrome). The most striking observation was, however, that up to 80% of the affected patients (compared with less than 5% in the normal control population, P less than 0.05) had multiple minor bone anomalies demonstrable by x-ray screening of the mandible, chest, and long bones. We suggest that a generalized (inherited or mutant) defect in growth regulation of connective tissue is the most important underlying cause for the DT. However, the other factors, including hormonal effects, trauma, and pregnancy contribute to the growth behavior of the tumor.
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PMID:The desmoid tumor. II. Analysis of factors possibly contributing to the etiology and growth behavior. 709 Oct 47

We have carefully examined four patients with desmoid tumor (DT) and their 31 relatives. In three of four cases, biopsies of the DT demonstrated low yet significant amounts of estrogen but not progesterone receptors in the tumor cytosol. In the fourth case, where the receptors were not demonstrable, the affected patient was a menopausal woman and the receptors may have been blocked by endogenous estrogen. Fourteen of their 31 relatives demonstrated multiple minor bone malformations in x-ray screening of the skeleton. The inheritance of these malformations was compatible with an autosomal dominant trait with variable penetrance. These findings are compatible with our suggestion that the basic underlying cause for DT is an inherited defect in growth regulation of the connective tissue. When a trauma is superimposed on such an individual, a DT may result. The growth of the tumor is, however, controlled primarily by sex hormones, estrogen predominance over progesterone being inducive to tumor growth.
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PMID:The desmoid tumor. III. A biochemical and genetic analysis. 709 Oct 48

Sixty-three patients with malignant and benign tumors of soft tissues were examined making use of magnetic resonance computer-aided tomography (MRT). This method was found effective in the diagnosis of soft tissue tumors, permitting the detection of tumor connection with the adjacent structures. In some cases MRT helped differentiate between malignant and benign soft tissue tumor growth, e.g. liposarcoma, malignant fibrous histiocytoma, lipoma, desmoid, hematoma. MRT may be effectively used in the diagnosis of soft tissue formations.
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PMID:[Magnetic resonance computerized tomography in the diagnosis of soft tissue neoplasms]. 780 81

The life-threatening event of early colorectal cancer in FAP patients may effectively be prevented by prophylactic colectomy. Desmoid tumors and periampullary carcinoma are now becoming the most frequent causes of death in FAP patients. Since the establishment of the Heidelberg polyposis registry in January 1991 we evaluated the frequency of desmoid tumors in 171 prospectively reexamined FAP patients. 29 patients (17%) with desmoid tumors were identified. In our series R0-resection with a wide security margin was performed in 12 cases, 3 of which developed a desmoid recurrence, 8 are free of desmoids and one treated for an intraabdominal desmoid states being well but refuses a radiological reevaluation. Tumor debulking was performed in 6 patients and led to an aggressive desmoid progression in 4 patients despite additional postoperative administration of tamoxifen and sulindac. Nonsurgical treatment with tamoxifen and sulindac seemed beneficial in 5 of 7 patients, 4 showed a stagnation of tumor growth, a reduction of an abdominal wall desmoid was documented in one female with a further intraabdominal desmoid. In life-threatening cases chemotherapy and radiation therapy may be considered. In two females radiation therapy resulted in a remarkable tumor reduction. The operative trauma of previous colectomy is considered the most relevant predisposing external factor inducing desmoid growth in FAP patients. 50% (11/22) of the desmoid tumors in our series were diagnosed within the first two years postoperatively, and 72% (18/22) of the desmoids developed within the first four years after colectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Desmoid tumors in patients with familial adenomatous polyposis (FAP). Clinical and therapeutic observations from the Heidelberg polyposis register]. 852 53

Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in beta-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to beta-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.
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PMID:Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor). 1131 76

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) regulate the degradation of extracellular matrix components and play important roles in the progression of select neoplastic processes. The locally invasive soft tissue tumor, aggressive fibromatosis (also called desmoid tumor), is caused by mutations resulting in beta-catenin-mediated T-cell factor (tcf)-dependent transcriptional activity. Because beta-catenin can regulate MMP expression, we investigated the expression of several MMPs and TIMPs in aggressive fibromatosis tumors that develop in Apc+/Apc1638N mice. Mmp-3 and Timp-1 were differentially regulated (5-fold and 0.5-fold, respectively) in tumors compared with normal fibrous tissue. Conditioned media from tumor cells showed an increased ability to degrade collagen, and inhibition of MMPs using GM6001 decreased the ability of the tumor cells to invade through Matrigel. Both the treatment of Apc/Apc1638N mice with GM6001 or crossing with a transgenic mouse that overexpresses Timp-1 resulted in a significant reduction in tumor volume. Surprisingly, overexpression of Timp-1 also resulted in a 50% increase in tumor number. Although TIMP-1 can induce growth stimulatory effects in some cell types, we found no difference in proliferation or apoptosis rate in cells from tumors that developed in the Timp-1-transgenic mice compared with mice that did not express the Timp-1 transgene, suggesting that TIMP-1 promotes aggressive fibromatosis tumor formation through an alternate mechanism. These data suggest that MMPs play a crucial role in regulating the invasiveness of mesenchymal cells and in modulating aggressive fibromatosis tumor progression. Because this is a locally invasive tumor, MMP inhibition could slow tumor growth and may prove to be an effective adjuvant therapy.
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PMID:Matrix metalloproteinase activity modulates tumor size, cell motility, and cell invasiveness in murine aggressive fibromatosis. 1531 22

Aggressive fibromatosis is a mesenchymal neoplasm associated with mutations, resulting in beta-catenin-mediated transcriptional activation. We found that plasminogen activator inhibitor-1 (PAI-1) was upregulated fourfold in aggressive fibromatosis. We investigated the ability of beta-catenin to regulate a PAI-1 reporter, and found that PAI-1 is an indirect target. To determine the role of PAI-1 in vivo, a mouse containing a targeted deletion in Pai-1 was crossed with a mouse that develops aggressive fibromatosis and gastrointestinal tumors (Apc/Apc1638N mouse). Pai-1 deficiency reduced the number of aggressive fibromatosis tumors formed, but not the number of gastrointestinal tumors. Deficiency of Pai-1 reduced tumor cell proliferation and motility rate. Although PAI-1 can alter cell motility by competing for a common binding site on vitronectin, blocking this site did not alter the motility rate. The number of cells moving through matrigel (invasion rate) did not change with Pai-1 deficiency, but because of the low motility rate the invasion index (invasion rate/motility) was increased in Pai-1-deficient cells. This suggests a proteolytic effect for PAI-1 regulating cell invasiveness. Our study found that, although PAI-1 has cellular effects that could inhibit or enhance tumor growth, on balance, it acts as a tumor enhancer in aggressive fibromatosis.
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PMID:Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor). 1567 49

The heterogeneity that soft tissue sarcomas (STS) exhibit in their clinical behavior, even within histological subtypes, complicates patient care. Histological appearance is determined by gene expression. Morphologic features are generally good predictors of biologic behavior, however, metastatic propensity, tumor growth, and response to chemotherapy may be determined by gene expression patterns that do not correlate well with morphology. One approach to identify heterogeneity is to search for genetic markers that correlate with differences in tumor behavior. Alternatively, subsets may be identified based on gene expression patterns alone, independent of knowledge of clinical outcome. We have reported gene expression patterns that distinguish two subgroups of clear cell renal carcinoma (ccRCC), and other gene expression patterns that distinguish heterogeneity of serous ovarian carcinoma (OVCA) and aggressive fibromatosis (AF). In this study, gene expression in 53 samples of STS and AF [including 16 malignant fibrous histiocytoma (MFH), 9 leiomyosarcoma, 12 liposarcoma, 4 synovial sarcoma, and 12 samples of AF] was determined at Gene Logic Inc. (Gaithersburg, MD) using Affymetrix GeneChip U_133 arrays containing approximately 40,000 genes/ESTs. Gene expression analysis was performed with the Gene Logic Genesis Enterprise System Software and Expressionist software. Hierarchical clustering of the STS using our three previously reported gene sets, each generated subgroups within the STS that for some subtypes correlated with histology, and also suggested the existence of subsets of MFH. All three gene sets also recognized the same two subsets of the fibromatosis samples that we had found in our earlier study of AF. These results suggest that these subgroups may have biological significance, and that these gene sets may be useful for sub-classification of STS. In addition, several genes that are targets of some anti-tumor drugs were found to be differentially expressed in particular subsets of STS.
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PMID:Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors. 1846 Feb 15


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