Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription factors GATA-4 and GATA-6 are expressed during normal adrenocortical development in mice and humans, and in vitro studies have linked them to adrenal steroidogenesis. GATA-4 is highly expressed in the adrenocortical tumors of gonadectomized mice, whereas GATA-6 is down-regulated in the tumor area. Based on these findings we studied GATA-4 and GATA-6 expression in 39 human adrenocortical tumors using RT-PCR, Northern analysis and immunohistochemistry. 6/18 adenomas and 4/11 carcinomas were positive for GATA-4 mRNA. GATA-6 mRNA was expressed in 19/19 adenomas and 9/10 carcinomas, and GATA-6 immunoreactivity was remarkably lower in adrenocortical carcinomas than in adenomas (p < 0.05). Some of the steroidogenically active human adrenocortical cells (NCI-H295R) were weakly positive for GATA-4, whereas steroidogenically inactive cells (ACT-1) were totally GATA-4 negative. In contrast, both cell lines expressed GATA-6. GATA expression patterns similar to the animal models can thus be observed in human adrenocortical tumors, but the pathophysiological significance of these findings remains to be elucidated.
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PMID:Transcription factors GATA-4 and GATA-6 in human adrenocortical tumors. 1566 45

5-Fluorouracil (5-FU) plus leucovorin (LV) has been the mainstay of treatment for colorectal cancer (CRC), with infused schedules more widely adopted in Europe and bolus schedules preferred in North America. However, the effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV on both sides of the Atlantic. Capecitabine generates 5-FU preferentially in tumor and is a well-established, first-line treatment for metastatic CRC. In this setting, capecitabine achieves a superior response rate, at least equivalent time to disease progression (TTP) and overall survival, and favorable safety compared with bolus 5-FU/LV. The benefits of capecitabine have been transfered into the adjuvant setting. Recent data from a large, international, randomized trial (Xeloda Adjuvant Chemotherapy Trial [X-ACT]) confirm that capecitabine (Xeloda, Roche Laboratories, Nutley, NJ) achieves favorable safety versus 5-FU/LV (Mayo Clinic regimen) and is at least as effective as IV 5-FU/LV in the adjuvant treatment of patients with resected stage III colon cancer. Capecitabine is also an effective and well-tolerated combination partner for oxaliplatin (XELOX) and irinotecan (XELIRI), achieving high efficacy with a good safety profile. An extensive phase III clinical trial program is further establishing the potential of the simplified capecitabine combinations to improve outcomes and unify treatment practices in the metastatic and adjuvant settings. New combinations with novel agents such as capecitabine/oxaliplatin plus erlotinib or bevacizumab are currently under investigation. Capecitabine has also shown promising activity and good tolerability in combination with radiotherapy in rectal cancer.
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PMID:Oral capecitabine: bridging the Atlantic divide in colon cancer treatment. 1572 5

Rhabdomyosarcoma is a highly malignant, small blue cell tumor characterized by muscle differentiation. With modern treatment, more than 70% of children and adolescents with this disease are cured. Adequate biopsy to obtain sufficient tissue for accurate diagnosis and molecular characterization is critical. Patients must be assessed for tumor extent; the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and Staging system is universally applied in North America. Multidisciplinary therapy is necessary to maximize cure rates. Local control relies on complete surgical excision when possible; those whose tumors are not completely excised and those with alveolar histology tumors require local irradiation to maximize local control. In North America, vincristine (Oncovin); Eli Lilly and Company, Indianapolis, http://www.lilly.com), dactinomycin (Cosmegen); Merck & Co., Inc., Whitehouse Station, NJ, http://www.merck.com), and cyclophosphamide are the standard chemotherapy agents. The IRS has used therapeutic window studies to confirm the predictive nature of preclinical xenograft models and to identify several new single agents and combinations of agents with activity in high-risk patient groups. Despite these efforts, the outcome for these high-risk patients remains poor. The next generation of Children's Oncology Group studies will evaluate the efficacy of topoisomerase-I inhibitors and dose-compression therapy approaches. New advances in molecular characterization of tumors, including gene-expression analysis, may identify new therapeutic targets that can be exploited by expanded preclinical drug discovery efforts, and hold the promise of revolutionizing risk-based therapies.
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PMID:Rhabdomyosarcoma: new windows of opportunity. 1607 19

The effect of dietary polyunsaturated fatty acids on the expression of differentiation and proliferation markers in Morris 3924A hepatoma cells was investigated. ACT/I rats were conditioned 10 days with diets enriched with linoleic acid or alpha-linolenic acid before subcutaneous hepatoma cell transplantation. After 19 days from the inoculum, the mRNA levels of liver-enriched transcription factors and of their target genes were quantified. Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. Only the alpha-linolenic acid-enriched diet was effective in reducing c-jun and increasing albumin mRNA levels. Since albumin is a C/EBPalpha target gene, C/EBPalpha gene transcription was evaluated at both protein and mRNA levels. It was found that alpha-linolenic acid-enriched diet did not enhance the C/EBPalpha mRNA content in hepatoma tissue while inducing C/EBPalpha protein expression with an isoform pattern similar to the hepatic phenotype. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by modulating C/EBPalpha gene expression at post-transcriptional level.
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PMID:Dietary PUFA modulate the expression of proliferation and differentiation markers in Morris 3924A hepatoma cells. 1629 Jan 14

Dentinogenic ghost cell tumor (DGCT) is considered as a neoplastic counterpart of the calcifying odontogenic cyst (COC). beta-catenin mutations have been described in COC suggesting a critical role in its histogenesis. In this study, we report a patient with DGCT contains a missense mutation on codon 3 (ACT --> TCT) of beta-catenin gene. Immunohistochemistry showed nuclear, cytoplasmic, and membranous accumulation of beta-catenin in the tumor cells. TUNEL assay showed positive signals in nucleated cells adjacent to the ghost cells. Our data suggest that beta-catenin plays an important role in the tumorigenesis of DGCT. DGCT may develop by an improper differentiation process coordinated by Wnt signaling pathway. Further studies are needed to determine the genotypic/phenotypic characteristics of ghost cell-containing odontogenic lesions.
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PMID:Investigation of the beta-catenin gene in a case of dentinogenic ghost cell tumor. 1717 1

Cancer immunotherapy with dendritic cell-tumor cell fusion hybrids induces polyclonal stimulation against a variety of tumor antigens, including unknown antigens. Hybrid cells can prime CTLs, which subsequently develop antitumor responses. The aim of this study was to enhance the known antitumor effect of hybrid vaccination (HC-Vacc) and hybrid-primed adoptive T-cell therapy (HC-ACT) using the poorly immunogenic Lewis lung carcinoma (LLC1) model. The strategy used was a combination of a double HC-Vacc alternating with HC-ACT (HC-Vacc/ACT). Using flat-panel volumetric computer tomography and immunohistochemistry, we showed a significant retardation of tumor growth (85%). In addition, a significant delay in tumor development, a reduction in the number of pulmonary metastases, and increased survival times were observed. Furthermore, the tumors displayed significant morphologic changes and increased apoptosis, as shown by up-regulation of gene expression of the proapoptotic markers Fas, caspase-8, and caspase-3. The residual tumor masses seen in the HC-Vacc/ACT-treated mice were infiltrated with CD4+ and CD8+ lymphocytes and showed elevated IFNgamma expression. Moreover, splenic enlargement observed in HC-Vacc/ACT-treated mice reflected the increased functionality of T cells, as also indicated by increased expression of markers for CTL activation, differentiation, and proliferation (Cd28, Icosl, Tnfrsf13, and Tnfsf14). Our findings indicate that the combination therapy of dendritic cell-tumor cell HC-Vacc/ACT is a very effective and a promising immunotherapeutic regimen against poorly immunogenic carcinomas.
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PMID:A combination hybrid-based vaccination/adoptive cellular therapy to prevent tumor growth by involvement of T cells. 1754 26

Serum levels of total prostate specific antigen (t-PSA) and PSA complexed to antichymotrypsin (PSA-ACT), as well as their corresponding density parameters were measured in prostate cancer (PC) candidates for radical prostatectomy. In these patients blood Chromogranin A (CgA) values were also recorded. The PSA-ACT recordings in presurgically characterized organ-confined disease were assumed to predict post-surgical staging better than t-PSA. If this proved correct the novel approach might contribute to the positive predictive value of Partin nomograms. In this prospective study 50 patients with clinically localized PC underwent staging pelvic lymphadenectomy and radical prostatectomy. The numerical values of the tPSA and PSA-ACT parameters were presurgically measured. The PSA and PSA-ACT densities (PSAD and ACTD) of the whole prostate were calculated by using transurethral ultrasound (TRUS) data. These preoperative results together with the CgA values were correlated with post-surgical pathological staging data. The relationships between serum tPSA, PSA-ACT, PSAD, ACTD, CgA and the final stage of prostatectomy specimens derived from the pathological data were analyzed. This preliminary study was performed on a relatively small number of patients who were characterized by a serum PSA <20 and a Gleason score (GS) < or =7. Nevertheless, the application of the logistic regression model showed both t-PSA and PSA-ACT to be superior to their density derivatives in predicting postsurgical pathological stage in PC patients who initially seemed to have localized prostate cancer. An elevation in serum CgA level, although rather infrequent at the early stages of PC is principally found in patients with higher Gleason score PC and was mostly associated with extracapsular tumor spread. Our results do not justify the substitution of PSA-ACT for t-PSA data in the Partin nomogram approach.
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PMID:Serum tPSA, cPSA, related density parameters and chromogranin A as predictors of positive margins after radical prostatectomy. 1769 53

Preclinical studies and initial clinical trials have documented the feasibility of adenoassociated virus (AAV)-mediated gene therapy for hemophilia B. In an 8-year study, inhibitor-prone hemophilia B dogs (n = 2) treated with liver-directed AAV2 factor IX (FIX) gene therapy did not have a single bleed requiring FIX replacement, whereas dogs undergoing muscle-directed gene therapy (n = 3) had a bleed frequency similar to untreated FIX-deficient dogs. Coagulation tests (whole blood clotting time [WBCT], activated clotting time [ACT], and activated partial thromboplastin time [aPTT]) have remained at the upper limits of the normal ranges in the 2 dogs that received liver-directed gene therapy. The FIX activity has remained stable between 4% and 10% in both liver-treated dogs, but is undetectable in the dogs undergoing muscle-directed gene transfer. Integration site analysis by linear amplification-mediated polymerase chain reaction (LAM-PCR) suggested the vector sequences have persisted predominantly in extrachromosomal form. Complete blood count (CBC), serum chemistries, bile acid profile, hepatic magnetic resonance imaging (MRI) and computed tomography (CT) scans, and liver biopsy were normal with no evidence for tumor formation. AAV-mediated liver-directed gene therapy corrected the hemophilia phenotype without toxicity or inhibitor development in the inhibitor-prone null mutation dogs for more than 8 years.
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PMID:Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. 1895 84

Distinguishing primary ovarian cancer from metastatic colorectal cancer is often difficult by a conventional pathological examination alone. We assessed the usefulness of p53 gene mutation analysis for the differential diagnosis of ovarian adenocarcinoma. A 66-year-old woman suffered multiple organ metastases, including the liver, para-aortic lymph node, and right ovary, following an operation for advanced sigmoid colon cancer. She underwent ovarian resection after effective chemotherapy against the liver and para-aortic lymph node cancer. Histological analysis suggested primary ovarian cancer. Therefore, we applied p53 gene mutation analysis for the differential diagnosis of primary versus metastatic ovarian cancer from sigmoid colon cancer. The direct sequence of the p53 gene demonstrated the same gene mutation in codon 211 (ACT to ATT) in both the sigmoid colon and ovarian cancers. According to the International Agency for Research on Cancer TP53 mutation database, this type of p53 mutation in colorectal cancer and ovarian cancer is 0.13% (5/3,693) and 0% (0/1,494), respectively. Therefore, we determined that the ovarian tumor was metastatic. Although p53 gene mutation analysis has been applied in some cases, this modality is very useful for the differential diagnosis of primary and metastatic cancer.
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PMID:Diagnosis of primary versus metastatic ovarian adenocarcinoma using p53 gene mutation analysis. 2051 5

One of the rarest situations regarding an adrenal incidentaloma is an adrenal cyst. We present the case of a 61-year-old male patient diagnosed with peritonitis. During surgery, a right adrenal tumor of 2 cm is discovered. The patient was referred to endocrinology. 6 months later the diameter of the tumor is 7 times bigger than the initial stage. It has no secretory phenotype, except for the small increase of serum aldosterone and the 24-h 17-ketosteroids. Open right adrenalectomy is performed and a cyst of 15 cm is removed. The evolution after surgery is good. The pathological exam reveals an adrenal cyst with calcifications and osteoid metaplasia. The immunohistochemistry showed a positive reaction for CD34 and ACT in the vessels and VIM in the stroma. The adrenal cysts are not frequent and represent a challenge regarding the preoperative diagnostic and surgical procedure of resection. The pathological exam highlights the major aspects.
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PMID:Giant adrenal cyst: case study. 2094 22


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