Biomedical subjects

H F Frierson

Publications and source records attributed to H F Frierson.

At least 37 records · Page 2Linked to original sources

PubMed1999

Loss of heterozygosity and lack of mutations of the XPG/ERCC5 DNA repair gene at 13q33 in prostate cancer.

BACKGROUND: Three regions of chromosome 13 were previously identified for having loss of heterozygosity (LOH) in human prostate cancer. One of them, at 13q33, was defined by LOH at markers D13S158 and D13S280. The XPG/ERCC5 gene, a DNA repair gene that when mutated in the germline leads to xeroderma pigmentosum, has been mapped to 13q33, within one megabase of D13S158 and D13S280. This paper describes LOH and mutational analysis of the XPG gene in human prostate cancers, in order to determine whether the XPG gene is involved in the development of prostate cancer. METHODS: LOH of the XPG gene was analyzed in 40 primary prostate cancers and 14 metastases by using the microsatellite assay, and its mutations were examined in 5 cell lines, 14 metastases, and 8 tumors with LOH at 13q33 by using the single-strand conformation polymorphism (SSCP)-direct DNA sequencing analysis. RESULTS: Four of the 29 (14%) informative primary tumors and 4 of 8 (50%) metastases showed LOH for the XPG gene. Analysis of the 8 tumors with LOH at the 13q33 region, 14 metastases, and 5 cell lines of prostate cancer revealed two polymorphisms but no mutation of the gene. The polymorphism in exon 2 did not change the amino-acid sequence of the XPG protein, but the exon 15 polymorphism altered codon 1104 from histidine to aspartic acid. The two polymorphisms also occurred in individuals without prostate cancer. CONCLUSIONS: LOH at XPG in prostate cancer supports the conclusion that the 13q33 region contains a gene important in the development of prostate cancer, while lack of mutations of the gene suggests that XPG is not the target gene involved.

Adult↗

PubMed1999

Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1.

Many of the alterations in the insulin-like growth factor (IGF) axis in prostatic disease have been associated with changes in the insulin-like growth factor binding proteins (IGFBPs), a multigene family of proteins that are thought to mediate the action of IGFs on target tissues. IGFBP-related protein 1 (rP1), also known as IGFBP-7 or mac25, is a recently described member of the IGFBP family, the biological function of which has yet to be completely ascertained. In this study, we analyzed the localization of IGFBP-rP1 in prostate cancer and benign prostate tissues using immunohistochemistry and a polyclonal antibody, T1A12, that is specific for IGFBP-rP1. The most intense staining was observed in nerves, whereas smooth muscle cells in the prostate stained weakly. Lymphocytes were always negative. When normal prostatic secretory epithelium was present, staining was usually absent. The lining secretory epithelium stained positively in 0 of 12 (0%) cases of benign prostatic hyperplasia, 57 of 63 (90.5%) primary adenocarcinomas, and 7 of 7 (100%) prostate cancer metastases. Prostatic intraepithelial neoplasia showed a similar pattern of staining to that observed for the invasive tumors. Analysis of Northern blots showed that none of the prostate cancer cell lines (LNCaP, C4, C4-2, C4-2B4, 9069E3, DU145, and PC3) expressed IGFBP-rP1 mRNA. This lack of expression was confirmed by immunohistochemistry of s.c.-generated tumor xenografts of LNCaP and C4-2 and by immunoblot on serum-free-conditioned media from all prostatic cell lines. In contrast to these results, tumor xenografts generated by direct intraosseous injection of LNCaP or C4-2 to bone marrow space resulted in tumors that stained positively for IGFBP-rP1. Our results show that IGFBP-rP1 is expressed in both in situ and invasive prostate neoplasms, but not typically in normal secretory or BPH epithelium; furthermore, the expression of IGFBP-rP1 can be induced in human prostate cancer cell lines in vivo on interaction with an appropriate host environment.

Carrier Proteins↗

PubMed1999

Methylation of the CD44 metastasis suppressor gene in human prostate cancer.

Previous studies demonstrated that CD44 is a metastasis suppressor gene for prostate cancer and that the expression of CD44 both at mRNA and protein levels is down-regulated during prostate cancer progression, with down-regulation being correlated with higher tumor grade, aneuploidy, and distant metastasis. In this study, we evaluated DNA hypermethylation as a potential mechanism accompanying this decreased CD44 expression in human prostate cancer. Nucleotide sequence analysis revealed a CpG island in the CD44 transcriptional regulatory region. We found that cytosine methylation of CD44 promoter occurs in CD44-negative prostate cancer cell line (i.e., LNCaP) but not in prostate cancer cell lines (i.e., TSU, PC3, and DU145) expressing this gene. In addition, we examined methylation status of CD44 in 84 matched normal and cancer prostate specimens. Hypermethylation of the 5' CpG island of CD44 gene was observed in 31 of 40 primary prostate cancer specimens, 3 of 4 distant organ site metastases obtained at autopsy from men who died of prostate cancer, and 4 of the 40 matched normal tissues. These results demonstrated that methylation of the 5' CpG island of CD44 gene is closely associated with transcriptional inactivation, resulting in a decreased expression of CD44 in human prostate cancer.

Adenocarcinoma↗

PubMed1999

Mutations of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors.

The c-kit gene encodes a transmembrane receptor kinase (KIT) which is expressed in the majority of human gastrointestinal stromal tumors (GISTs), a subtype of gastrointestinal mesenchymal neoplasms. A previous study identified mutations in the juxtamembrane (JM) domain of c-kit in five of six GISTs (Science 279: 577, 1998). To better define the frequency and spectrum of c-kit gene mutations in mesenchymal neoplasms of the GI tract that had been characterized for KIT protein expression, we examined archived tissue samples for mutations in the JM domain by PCR amplification and DNA sequencing. c-kit JM domain mutations were found in nine of 56 mesenchymal tumors (46 GISTs, eight leiomyomas, two leiomyosarcomas) and occurred exclusively in GISTs (21%). Seven of the nine mutations consisted of intragenic deletions of one to 19 codons. There was one insertion mutation that added 12 codons and one missense mutation (Val560Asp). None of the mutations disrupted the downstream reading frame of the gene. The single missense mutation (Val560Asp) is very similar to the only other missense mutation reported in GISTs (Val599Asp). Of the 46 GISTs, 43 were strongly positive for KIT protein expression and negative for diffuse expression of desmin. Neither KIT expression nor gene mutations were found in gastrointestinal leiomyomas or leiomyosarcomas. We conclude that mutation of the c-kit JM domain does not occur in gastrointestinal mesenchymal neoplasms with well developed-smooth muscle differentiation, and is restricted to GISTs. However, since these mutations are only found in a minority of GISTs, further investigation into the mechanisms of c-kit gene activation in this group of neoplasms is warranted.

Amino Acid Sequence↗

PubMed1999

Activation of mitogen-activated protein kinase associated with prostate cancer progression.

Using an antibody specific for dually phosphorylated extracellular-regulated kinases 1 and 2, we have examined 82 primary and metastatic prostate tumor specimens for the presence of activated mitogen-activated protein (MAP) kinase. Nonneoplastic prostate tissue showed little or no staining with activated MAP kinase antiserum. In prostate tumors, the level of activated MAP kinase increased with increasing Gleason score and tumor stage. In a separate analysis, tumor samples from two patients showed no activation of MAP kinase before androgen ablation therapy; however, following androgen ablation treatment, high levels of activated MAP kinase were detected in the recurrent tumors. Collectively, these data suggest an increase in the activation of the MAP kinase signal transduction pathway as prostate cancer progresses to a more advanced and androgen-independent disease.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1999

Activating c-kit gene mutations in human germ cell tumors.

The c-kit gene encodes a tyrosine kinase receptor (KIT) that is required in normal spermatogenesis and is expressed in seminomas and dysgerminomas, a subset of human germ cell tumors (GCTs). To determine whether activating mutations of the c-kit gene occur in GCTs, primary tissue samples of 33 testicular and ovarian tumors were examined for mutations in the juxtamembrane and phosphotransferase domains by polymerase chain reaction amplification and DNA sequencing. A novel missense mutation (D816H) was found in the phosphotransferase domain in tumors of seminoma/dysgerminoma differentiation. The c-kit alleles in nonneoplastic tissues from these patients were wild type, suggesting that the mutant alleles were acquired and selected for during malignant transformation. In cell transfection experiments, the D816H mutant protein was a constitutively activated kinase and was constitutively phosphorylated on tyrosine residues. This is the first description of an activating c-kit mutation in GCTs and is evidence that the KIT signal transduction pathway is important in the pathogenesis of neoplasms with seminoma differentiation.

Amino Acid Substitution↗

PubMed1999

Altered expression of gamma-glutamyl transpeptidase in human tumors.

Elevated levels of gamma-glutamyl transpeptidase (GGT) activity and intracellular glutathione in tumor cells have been correlated with resistance to several classes of chemotherapeutic drugs. In this study, the first comprehensive analysis of GGT expression in human malignant neoplasms, 451 tumors were immunostained with an antibody directed against a c-terminus peptide of the human GGT protein. Analysis of the immunostaining revealed that GGT was expressed in 22 of 44 lung carcinomas and 16 of 22 ovarian surface epithelial carcinomas, although normal pulmonary and ovarian epithelium are GGT-negative. The tumor samples were obtained from patients before the start of therapy; therefore, GGT was not induced by radiation or chemotherapy. There was no GGT expression in mesotheliomas, Hodgkin's disease, non-Hodgkin's lymphomas, melanomas, basal cell carcinomas, and most soft tissue sarcomas, all of which are derived from GGT-negative cells. Carcinomas arising from some GGT-positive epithelium retained their GGT-positive phenotype. These included renal cell carcinomas, hepatocellular and cholangiocarcinomas, and carcinomas of the prostate and thyroid whereas both pancreatic adenocarcinomas and infiltrating carcinomas of the breast showed a wide range of GGT expression. Further studies are underway to determine whether expression of GGT plays a role in the inherent resistance of some tumors to alkylating agents and other classes of chemotherapeutic drugs.

Female↗

PubMed1999

Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas.

The chromosomal locus 9p21 contains the p16(INK4a/CDKN2/MTS1) tumor suppressor gene that has been implicated in a variety of tumor types, including carcinomas of the head and neck, esophagus, and pancreas. To determine whether the loss of this gene is involved in salivary gland cancers, 35 carcinomas and paired nonneoplastic specimens were analyzed for loss of heterozygosity (LOH) of polymorphic genetic markers located in the region of interest. Five types of salivary gland tumors were studied: mucoepidermoid carcinoma, salivary duct carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, and polymorphous low-grade adenocarcinoma. Seven of 9 salivary duct carcinomas showed LOH of 1 or more polymorphic markers. In 1 case of salivary duct carcinoma with LOH, we confirmed a deletion of bp 240-254 within exon 2. In addition, another salivary duct carcinoma showed a homozygous deletion of p16 in differential polymerase chain reaction analysis. Loss of heterozygosity was found in 1 of 10 adenoid cystic carcinomas and 1 of 8 mucoepidermoid carcinomas and was absent in the remaining subtypes. No mutations in exon 1 or exon 2 or homozygous deletion of p16 were found in these 2 particular neoplasms with LOH. These results suggest that inactivation of p16 is important in the development or progression of at least some salivary duct carcinomas, but we found no evidence that its alteration plays a role in the other subtypes examined.

Adenocarcinoma↗

PubMed1999

Detection of the alpha-subunit of inhibin in trophoblastic neoplasia.

Placental trophoblasts are the primary source of serum inhibin during pregnancy. We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and compare the results with those for established markers of trophoblastic differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three gestational, one testicular, one mediastinal), and five placental site trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha-subunit of inhibin, hPL, and beta-hCG. Additionally, six first-trimester placentas were immunolabeled with antibody to inhibin alone. Trophoblastic subpopulations were assessed for the number of positive cells (1% to 24% = 1+,25% to 49% = 2+,50% to 74% = 3+, 75% to 100% = 4+). Immunolabeling in term placenta and HM was similar, because beta-hCG was the most sensitive marker (4+) of syncytiotrophoblasts followed by inhibin (3-4+) and hPL (2-3+). Immunolabeling of syncytiotrophoblasts in CC was similar to that in term placenta and HM, except for negative hPL staining in two cases. In HM, inhibin labeling of intermediate trophoblasts (2-3+) was less than that for hPL (3-4+). In CC, inhibin and hPL labeling of intermediate trophoblasts was more variable with negative hPL reactivity in two cases. Inhibin and hPL did not stain cytotrophoblasts. In PSTT, inhibin immunolabeling was a better marker than hPL in two cases, inferior in two, and similar in one. Inhibin labeling of syncytiotrophoblasts was less than that for beta-hCG, but did not have the often marked background staining that was present with beta-hCG. Immunolabeling of trophoblast subpopulations for inhibin was similar between first-trimester placenta, term placenta, and HM. We conclude that inhibin is a useful immunohistochemical marker of trophoblastic neoplasia and should be included in the antibody panel with beta-hCG and hPL.

Adult↗

PubMed1999

Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin.

Previous studies have shown that the enzyme-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.

Adolescent↗

PubMed1999

Unusual case of non-exophytic invasive penile squamous cell cancer arising from a chronic sinus tract.

We present an unusual case of an extremely well-differentiated but deeply invasive squamous cell carcinoma of the penis without an obvious external lesion, arising from a chronic draining sinus tract. This case highlights how a confounding clinical history, physical examination and initial biopsies may lead to a significant delay in diagnosis. This delay may have resulted in tumour growth and the need for a more extensive partial penectomy than would have occurred had the diagnosis been made more promptly. Finally, this case demonstrates the key diagnostic utility of deep core biopsies of the penis in situations where a cutaneous lesion does not exist.

Adult↗

PubMed1999

Detection of Helicobacter pylori DNA in fecal samples from infected individuals.

Stool, gastric biopsy, and serum samples were collected from 22 subjects. DNA from stool was extracted, amplified, and hybridized with primers specific for the 16S rRNA gene of Helicobacter pylori. DNA from gastric biopsy specimens was analyzed similarly for comparison. Universal primers were used to confirm successful extraction of DNA from samples. Histologic, serologic, and DNA analyses were scored in a blinded fashion. Universal primer amplification verified successful DNA extraction from all stool and gastric tissue specimens. The gastric tissue DNA assay was positive for H. pylori in 11 of the 22 subjects, correlating completely with histologic and serologic results. Stool DNA was positive for H. pylori by our molecular assay in 8 of these 11 H. pylori-positive subjects. All subjects who were negative by histologic, serologic, and gastric tissue DNA analyses were also negative by stool DNA analysis. Compared to histology, serology, and gastric tissue DNA analyses, the sensitivity of our stool DNA assay was 73%, with a specificity of 100%.

DNA, Bacterial↗

PubMed1999

Molecular determination of surgical margins using fossa biopsies at radical prostatectomy.

PURPOSE: Status of the surgical margins after radical prostatectomy is a key factor for predicting postoperative outcome. Current methods used to determine margin status are tedious, costly and vary among institutions. Sensitive and inexpensive detection of prostate cells in the circulation of patients with prostate cancer has been achieved using reverse transcriptase (RT) polymerase chain reaction (PCR) for prostate specific antigen and prostate specific membrane antigen. Therefore, we designed and tested a novel and objective molecular assay for assessing surgical margins at radical prostatectomy based on the detection of prostate specific markers using RT-PCR. We also compared this assay to standard pathological examination. MATERIALS AND METHODS: A total of 30 consecutive patients with local prostate cancer underwent radical prostatectomy. At the completion of gland excision 5 biopsies of the prostatic fossa were obtained for histopathological and molecular analysis. We performed RT-PCR analysis for prostate specific antigen and prostate specific membrane antigen messenger ribonucleic acid in these biopsy specimens, and compared the results with pathological stage. Men free of prostate cancer who underwent radical cystoprostatectomy for bladder cancer or abdominoperineal resection for rectal cancer served as controls. RESULTS: There were positive molecular margins in all patients with positive margins and/or extracapsular extension. No controls had a positive molecular assay. In 4 of 16 patients (25%) histopathological evaluation revealed organ confined disease but biopsies were positive by the molecular assay, including those in 2 (50%) who had been treated with neoadjuvant hormonal therapy before surgery because of a higher estimated risk of extracapsular disease. Results in 4 cases were uninformative. CONCLUSIONS: Our results with an objective molecular assay aimed at assessing surgical margins after radical prostatectomy reveal an excellent correlation with conventional pathological analysis. In addition, molecular assessment of the prostatic fossa identifies patients in whom extracapsular disease may have been unidentified by conventional pathological examination. In addition, this assay yields clues to why neoadjuvant hormonal treatment before radical prostatectomy does not seem to decrease the biochemical failure rate in these patients. Larger studies with longer followup are required to determine the prognostic significance of these positive molecular margins.

Adenocarcinoma↗

PubMed1999

Three distinct regions of allelic loss at 13q14, 13q21-22, and 13q33 in prostate cancer.

Chromosome 13 is one of the most frequently altered chromosomes in cancer, including carcinoma of the prostate. Two known tumor suppressor genes, RB1 and BRCA2, map to chromosome 13; however, recent reports suggest that unknown genes on 13q are more likely to be involved in the development of prostate cancer. In order more fully to define the genetic changes on chromosome 13 in prostate neoplasms, we analyzed 27 polymorphic microsatellite markers spanning the q arm for loss of heterozygosity in 40 primary tumors and in metastases from 11 other patients who died of prostate cancer. Of the 40 primary tumors, 23 (58%) showed LOH for at least one marker. Three distinct regions at q14, q21-22, and q33, defined by markers D13S267-->D13S153, D13S166-->D13S1225, and D13S259-->D13S274, showed the most frequent LOH, suggesting their involvement in the development of prostate cancer. For the 12 patients whose tumors showed LOH at these markers, the average age at diagnosis was 58 years, which was younger than that (63 years, P < 0.05) for the 28 patients whose tumors lacked LOH. Ten of the 11 (91%) metastases showed LOH with one or more markers. Two of the three most frequently deleted regions (i.e., q14 and q21-22) in the primary tumors and markers linked to the RB1, BRCA2, and EDNRB genes showed high frequencies (56-71%) of LOH in metastases. These results demonstrate that allelic loss on chromosome 13 at q14, q21-22, and q33 occurs in a subset of primary prostate tumors and is a frequent event in metastatic lesions of prostate cancer.

Adult↗

PubMed1999

KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma.

The c-kit proto-oncogene encodes a transmembrane receptor tyrosine kinase (KIT), which is expressed in several normal human tissues, especially mast cells and interstitial cells of Cajal. Expression of KIT has been noted in several types of neoplasms and gene mutation has been shown as a mechanism of c-kit oncogene activation in some tumors. Recently, a single adnexal adenoid cystic carcinoma (ACC) was reported to demonstrate KIT expression, however, examination of KIT expression or c-kit mutation in ACC of salivary glands has not been performed. We examined archival tissue samples from 30 ACC of major and minor salivary glands for KIT protein expression by immunohistochemistry with a polyclonal antibody and c-kit gene mutation by polymerase chain reaction amplification and DNA sequencing. KIT protein expression was noted in 90% of ACCs. An association between the presence of at least 50% KIT positive neoplastic cells and Grade 3 ACC or a solid growth pattern was observed (P < .05). KIT expression in normal or nonneoplastic salivary gland tissue was absent. No c-kit juxtamembrane domain (exon 11) or phosphotransferase domain (exon 17) mutations were found in any of the tumors examined. In conclusion, KIT protein expression is correlated with tumor grade of salivary ACC. However, gene mutation of exon 11 or exon 17 is not a mechanism of c-kit activation in these neoplasms.

Adult↗

PubMed1998

PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate.

Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.

Adult↗

PubMed1998

Enhanced gamma-glutamyl transpeptidase expression and selective loss of CuZn superoxide dismutase in hepatic iron overload.

Liver injury caused by iron overload is presumed to involve lipid peroxidation and the formation of products such as 4-hydroxynonenal (4HNE), which has been implicated in hepatic fibrogenesis. Cellular antioxidants that modulate the formation and detoxification of compounds such as 4HNE may represent important protective mechanisms involved in the response to iron overload. This study examines the relationship between 4HNE, collagen content, and antioxidant defenses in the livers of rats fed carbonyl iron for 10 weeks. Iron-loading resulted in significant increases in iron (8.8-fold), 4HNE (1.7-fold), and hydroxyproline (1.5-fold). Total glutathione content was unchanged by iron, but gamma-glutamyl transpeptidase activity (GGT) increased sixfold and CuZn superoxide dismutase (CuZnSOD) activity decreased >9%. GGT colocalized with iron deposition and was associated with increased GGT mRNA. Decreased CuZnSOD activity was paralleled by a reduction in CuZnSOD protein on Western blot and immunohistochemistry, but no decrease in CuZnSOD mRNA. Glutathione S-transferase (GST) and Mn superoxide dismutase (MnSOD) activities were also significantly increased by iron loading. These results demonstrate that iron overload significantly alters the expression of antioxidant enzymes associated with glutathione (GGT and GST) and superoxide metabolism (CuZnSOD and MnSOD). Furthermore, the localized induction of GGT may enhance detoxification of lipid peroxidation-derived aldehydes via glutathione-dependent pathways in iron-loaded hepatocytes. These alterations in antioxidant defenses may represent an adaptive response, limiting accumulation 4HNE, and thus, stimulation of collagen synthesis, accounting for the mild fibrogenic response seen in this model of iron overload.

Aldehydes↗

PubMed1998

Consistent genetic alterations in xenografts of proximal stomach and gastro-esophageal junction adenocarcinomas.

The genetic alterations underlying the development of gastric and gastro-esophageal carcinoma remain largely undefined. DNA copy number changes were determined by comparative genomic hybridization in eight xenografts of proximal gastric and gastro-esophageal junction adenocarcinomas of the intestinal type. All tumors exhibited DNA copy number changes, with a total of 139 changes detected (range, 11-24 per tumor; mean = 17), indicating numerous and widespread alterations within these cancers. Gains (65%) in DNA copy number were more frequent than losses (35%). Our most striking finding was gain (all eight cases) or high-level amplification (four cases) in 20q, with a minimal common overlapping region at 20q13. Other frequent gains were observed at 6p, 7q, and 17q (six cases each) and at 1q, 2q, and 8q (five cases each). Frequent losses were observed at 4q and 5q (six cases each) and at 9p (five cases). No differences in DNA copy number changes were seen in tumors arising from the gastro-esophageal junction compared to those of the proximal stomach. The presence of common and consistent DNA copy number changes in these tumors implicate a number of chromosomal regions that may harbor important genes that are involved in tumorigenesis of the proximal stomach and gastro-esophageal junction.

Adenocarcinoma↗