Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor and antimetastatic activities of the water-soluble peptidoglycan monomer GlnNAc-Mur-NAc-L-Ala-D-iso-Gln-meso-diamminopimelic acid (omega-NH2)-D-Ala-D-Ala (PGM), which has immunostimulant effects, have been evaluated in CBA mice bearing MCa mammary carcinoma. The antineoplastic effects of PGM depend strictly on the dosage and treatment schedule used. Though a significant inhibition of the primary tumor growth is observed over a wide range of dosage, only the IV administration of daily doses of 50 mg/kg/day on days 1, 5, 10, 15 inhibits spontaneous lung metastasis formation and in parallel prolongs the survival time of the treated mice. The magnitude of the antimetastatic effects of PGM depends on the degree of dissemination of the tumor, and is greater when the number of metastatic foci is low. Examination of the therapeutic potential of PGM in combination with surgery has further indicated that the timing of administration plays an important role in the overall effectiveness of this substance. A 5-day interval is necessary between two consecutive injections for the induction of significant increases of the survival times.
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PMID:Antitumor and antimetastatic activity of the immunoadjuvant peptidoglycan monomer PGM in mice bearing MCa mammary carcinoma. 656 78

P16 was originally discovered by its ability to interact with CDK4 and to specifically inhibit the catalytic activity of the CDK4/D1 kinase. Increased attention has focused on the p16 gene because of its location on chromosome 9p21, a region involved in chromosomal rearrangements in a large number of tumor types. The p16 gene is also mutated in a large number of tumor cell lines and primary tumor cells. Furthermore, linkage analysis studies suggest that the p16 gene is involved in familial melanoma susceptibility. Due to the oncogenic potential of mutations in this tumor suppressor, it is important to identify and characterize those mutations which alter p16 activity. We have performed a systematic analysis of melanoma associated p16 mutants and of mutants generated in charge to Ala mutagenesis. Using microtiter plate assays to measure both p16-cdk4 binding and cdk4/D1 kinase activity, we show here that the melanoma associated mutants are defective, as are some of the Ala mutants. These results support the idea that p16 mutation, via its deregulation of the cdk4/D1 pathway, is of biological significance in the development of melanoma. Furthermore, we have defined a region within the p16 molecule in which changes are likely to result in a defective protein.
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PMID:Biochemical and mutagenic analysis of the melanoma tumor suppressor gene product/p16. 747 20

Liver metastases are not uniformly fatal. A group of patients exists that will benefit from therapy directed at the liver either with surgical resection, intra-arterial chemotherapy or a combination of both. (Fig 2) All patients should be evaluated for the possibility of surgical resection since it can provide a 5-year survival of 25 to 40%, or hepatic arterial infusion therapy since response rates are higher and toxicity lower than systemic chemotherapy. When metastases are discovered simultaneously with the primary tumor, consideration should be given to concomitant treatment of both the primary and the liver if the patient is a suitable operative candidate and the resection will not entail more than a wedge or a left lateral lobe resection. Metastases discovered on follow-up of the primary tumor may be immediately addressed with surgical resection or hepatic artery infusion pump placement if the disease-free interval has been greater than 1-2 years. When the disease free interval has been less than a year, systemic chemotherapy is probably more prudent to allow time for manifestation of extra hepatic disease. If no extra-hepatic metastases become manifested after 6 months of systemic chemotherapy, then regional chemotherapy or resection should be considered. Intrahepatic progression on systemic chemotherapy is not a contraindication to hepatic artery infusion chemotherapy since the metastases may still respond. This approach allows patients manifesting extrahepatic disease while on systemic chemotherapy to be spared an operative procedure.
Ala Med 1994 Feb
PMID:Colorectal cancer hepatic metastases: the surgeons role. 804 81

Over a 1-year period (1994-1995), 75 children with brain neoplasms were evaluated with a new automated magnetic resonance spectroscopy (MRS) software package called Proton Brain Exam/Single-Voxel (PROBE/SV) to determine the efficacy of this modality in children. The children ranged in age from newborn to 17 years and were comprised of 30 girls and 45 boys. The types of brain neoplasms consisted of 45 astrocytomas, 4 medulloblastomas, 2 ependymomas, 3 craniopharyngiomas, 3 germinomas, 1 pineoblastoma, 2 teratomas, 1 choroid plexus papilloma, 4 meningiomas, 2 astroblastomas, 3 rhabdoids, and 5 metastases from primary brain neoplasms. All children underwent magnetic resonance imaging (MRI) at the same setting as the MRS examination. The MRS examination was performed with the stimulated echo acquisition mode (STEAM) pulse sequence in all children, and occasionally the point resolved spectroscopy (PRESS) sequence also was used. Qualitative spectra were obtained in all children, and at times quantification data also were obtained. We found that our spectra over the brain neoplasms were consistent with the MRS findings of brain neoplasms in the literature. There was markedly elevated choline with markedly decreased or absent N-acetylasparate and at times elevated lactate and lipid peaks. In children with meningiomas, there was also an elevated alanine peak. We found MRS to be extremely useful in 1) characterizing a brain mass as a neoplasm, 2) differentiating radiation necrosis and radiation-induced meningiomas from the recurrent primary tumor, 3) following treatment response of the primary neoplasm, 4) differentiating residual or recurrent primary neoplasm from postsurgical changes, and 5) identifying inactive neoplasms or neoplasms in remission.
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PMID:Magnetic resonance spectroscopy (MRS) in the evaluation of pediatric brain tumors, Part II: Clinical analysis. 896 91

Progression of prostate cancer during endocrine therapy is a major clinical problem, the molecular mechanisms of which remain poorly understood. Amplification of the androgen receptor (AR) gene was recently described in recurrent prostate carcinomas from patients who had failed androgen deprivation therapy. To evaluate the hypothesis that amplification of the AR gene is a cause for the failure of androgen deprivation therapy in prostate cancer, we studied whether AR amplification leads to gene overexpression, whether the amplified AR gene is structurally intact, and whether tumors with AR amplification have distinct biological and clinical characteristics. Tumor specimens were collected from 54 prostate cancer patients at the time of a local recurrence following therapy failure. In 26 cases, paired primary tumor specimens from the same patients prior to therapy were also available. Fifteen (28%) of the recurrent therapy-resistant tumors, but none of the untreated primary tumors, contained AR gene amplification as determined by fluorescence in situ hybridization. According to single-stranded conformation polymorphism analysis, the AR gene was wild type in all but one of the 13 AR amplified cases studied. In one tumor, a presumed mutation in the hormone-binding domain at codon 674 leading to a Gly --> Ala substitution was found, but functional studies indicated that this mutation did not change the transactivational properties of the receptor. AR amplification was associated with a substantially increased level of mRNA expression of the gene by in situ hybridization. Clinicopathological correlations indicated that AR amplification was most likely to occur in tumors that had initially responded well to endocrine therapy and whose response duration was more than 12 months. Tumors that recurred earlier or those that showed no initial therapy response did not contain AR amplification. The median survival time after recurrence was two times longer for patients with AR amplification in comparison to those with no amplification (P = 0.03, Willcoxon-Breslow test). In conclusion, failure of conventional androgen deprivation therapy in prostate cancer may be caused by a clonal expansion of tumor cells that are able to continue androgen-dependent growth despite of the low concentrations of serum androgens. Amplification and the increased expression of a wild-type AR gene may play a key role in this process.
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PMID:Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. 900 May 75

A 60-kDa glycoprotein named metanestin was identified by molecular cloning. The glycoprotein had a twice-repeated motif of Pro-Gly-Pro-Gly and carried metastasis-associated carbohydrate epitopes. The antibody to the protein portion of metanestin strongly reacted with lymph-node metastasis of transitional-cell carcinoma of the urinary bladder, but the reactivity to the primary tumor was generally weaker and the normal urothelium was scarcely reactive. Thus both metanestin and the carbohydrate on it showed metastasis-associated expression. In addition, we identified a 100-kDa glycoprotein with a 4-times-repeated motif of Pro-Ala-Pro-Ala. The antibody to the 100-kDa glycoprotein showed reactivity similar to that to metanestin.
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PMID:Metanestin, a glycoprotein with metastasis-associated expression in transitional cell carcinoma of the urinary bladder. 903 62

Carcinoma cell lines are frequently refractory to transforming growth factor-beta (TGF beta)-mediated cell cycle arrest. Whether and how TGF beta signaling is disrupted in the majority of human tumors, however, remains unclear. To investigate whether TGF beta signaling might be disrupted by inactivation of the key signaling molecule, the TGF beta type I (T beta R-I) receptor, and whether or not T beta R-I inactivation is associated with late stage disease, we conducted a comprehensive structural analysis of the T beta R-I gene in fine-needle aspirates of 23 head-&-neck cancer metastases. We encountered 4 different mutations of T beta R-I, 3 of which have not been previously identified. In 1 case, we found a somatic intragenic 4-bp deletion predicting for a truncation of the receptor protein. This is the first example of a true loss-of-function mutation of T beta R-I in a human epithelial neoplasm. In 2 other cases, we identified missense mutations located between the juxtamembrane- and serine-threonine kinase domains. One of these resulted in an alanine-to-threonine substitution (A230T), which disrupts receptor signaling activity by causing rapid protein degradation within the endoplasmatic reticulum. This represents a novel mechanism of inactivation of a TGF beta signaling intermediate. Finally, we identified a serine-to-tyrosine substitution at codon 387 (S387Y) in a metastasis but not in the corresponding primary tumor. We had previously shown this S387Y mutant to be predominantly associated with breast cancer metastases and to have a diminished ability to mediate TGF beta-dependent signaling. In aggregate, these findings provide further support for the hypothesis that inactivation of the TGF beta signaling pathway occurs in a significant subset of human cancers.
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PMID:Novel inactivating mutations of transforming growth factor-beta type I receptor gene in head-and-neck cancer metastases. 1147 74

Yet meningiomas have characteristic neuroimaging features, some other lesions are still confusing with meningiomas. The aim of this study was trying to find the typical (1)H-MRS metabolic factors of histologic subtyped meningiomas, schwannomas, metastases, and other brain tumors for differential diagnosis among them. (1)H-MRS using STEAM (TE/30 ms, TR/2 sec) and PRESS (TE/288 ms, TR/2 sec) sequences were performed on 44 untreated brain tumors. Obtained metabolic patterns from the typical spectra of meningioma, schwannoma, metastasis were compared with each other or other brain tumors to evaluate the usefulness for diagnosis between them. Alanine(Ala) was observed in 15 cases of the 19 meningiomas with a little variation to three histologic subtypes, while minimal lipids were observed in every 19 meningiomas. Elevated glutamate/glutamine(Glx) was detected in 12 cases of the meniningiomas. Increased myo-inositol(mI) was detected in 11 cases of the 13 schwannomas. Dominant lipids signals as well as long-T2 lipids were detected in every metastasis in conjunction with elevated choline (Cho). Enhanced Glx was observed in 4 cases of the 8 metastases without correlation of primary tumor site or types. Hemangiopericytoma showed different spectral patterns from typical meningiomas: only dominant Cho, minimal lipids and absence of Ala or Glx signals. These metabolic patterns in typical tumors may provide a basis for differential diagnosis (average value of chi(2) = 23.33, p < 0.01) between meningiomas and schwannomas as well as metastases. However proton spectral distinction among the different histologic subtypes of meningiomas was not definite.
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PMID:(1)H-MRS metabolic patterns for distinguishing between meningiomas and other brain tumors. 1291 98

The overexpression of the epidermal growth factor receptor (EGFR) and HER-2 underpin the growth of aggressive breast cancer; still, it is unclear what governs the regulation of these receptors. Our laboratories recently determined that the Y-box binding protein-1 (YB-1), an oncogenic transcription/translation factor, induced breast tumor cell growth in monolayer and in soft agar. Importantly, mutating YB-1 at Ser(102), which resides in the DNA-binding domain, prevented growth induction. We reasoned that the underlying cause for growth attenuation by YB-1(Ser(102)) is through the regulation of EGFR and/or HER-2. The initial link between YB-1 and these receptors was sought by screening primary tumor tissue microarrays. We determined that YB-1 (n = 389 cases) was positively associated with EGFR (P < 0.001, r = 0.213), HER-2 (P = 0.008, r = 0.157), and Ki67 (P < 0.0002, r = 0.219). It was inversely linked to the estrogen receptor (P < 0.001, r = -0.291). Overexpression of YB-1 in a breast cancer cell line increased HER-2 and EGFR. Alternatively, mutation of YB-1 at Ser(102) > Ala(102) prevented the induction of these receptors and rendered the cells less responsive to EGF. The mutant YB-1 protein was also unable to optimally bind to the EGFR and HER-2 promoters based on chromatin immunoprecipitation. Furthermore, knocking down YB-1 with small interfering RNA suppressed the expression of EGFR and HER-2. This was coupled with a decrease in tumor cell growth. In conclusion, YB-1(Ser(102)) is a point of molecular vulnerability for maintaining the expression of EGFR and HER-2. Targeting YB-1 or more specifically YB-1(Ser(102)) are novel approaches to inhibiting the expression of these receptors to ultimately suppress tumor cell growth.
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PMID:Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. 1665 43

We studied the effects of four synthetic amides of betulonic acid containing amino acid fragments (d,l-alpha-alanine, beta-alanine, and their methyl esters) on the rate of growth and metastatic dissemination of transplantable Lewis lung carcinoma in C57Bl/6 mice. The test compounds were administered intragastrically in a single dose of 500 mg/kg. 3-[-oxo-20(29)-lupen-28-oilamino]-propionic acid suppressed primary tumor growth (by 26%) and decreased the number of lung metastases (by more than 2 times). Antitumor and antimetastatic activity of triterpenoids decreased after methylation of the amino acid fragment in betulonic acid.
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PMID:Antitumor and antimetastatic effects of betulonic acid amides in mice with transplantable lewis carcinoma. 1736 6


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