Loss of p16 INK4 expression in invasive squamous cell carcinoma of the uterine cervix is an adverse prognostic marker.
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Biomarkers, Tumor↗
Biomedical subjects
T Ehlen
Publications and source records attributed to T Ehlen.
Coexpression of hepatocyte growth factor-Met: an early step in ovarian carcinogenesis?
Since autocrine regulation of HGF-Met is implicated in many forms of human cancer, we investigated whether the predisposition to develop ovarian cancer in women with hereditary ovarian cancer syndromes involves changes in the expression of HGF-Met by the tissue of origin of epithelial ovarian cancers, the ovarian surface epithelium (OSE). We compared cultures of normal OSE from women with (FH-OSE) (n=20) and with no (NFH-OSE) (n=48) family histories of ovarian cancer, SV40 Tag immortalized OSE lines (IOSE, n=5) and ovarian cancer cell lines (n=3). Cultures derived from 21/22 women with NFH-OSE and 13/13 women with FH-OSE expressed Met mRNA initially. After two to three passages, Met was downregulated in 37% of NFH-OSE cultures but persisted in 100% of FH-OSE cultures and ovarian cancer lines, like other epithelial differentiation markers that are stabilized in FH-OSE and neoplasia. HGF and Met mRNA were concomitantly expressed by NFH-OSE from only three of 32 women but in FH-OSE from eight of 13 women, and also in five of five IOSE and two of three ovarian cancer lines. Conditioned media from FH-OSE, but not NFH-OSE, contained immunoreactive HGF and induced cohort migration which was inhibited by neutralizing HGF antibody. Several signaling molecules of the PI3K pathway, including Akt2 and p70 S6K, were constitutively activated in FH-OSE from six of six women but in NFH-OSE from only four of eight women. Exogenous HGF was mitogenic in OSE, and that effect was regulated through the MAP kinase (ERK1/ERK2) and FRAP/p70 S6K pathways. The proliferative response to HGF was greater in NFH-OSE than in FH-OSE cultures. The results show that FH-OSE cultures differ from NFH-OSE by increased stability of Met expression and by HGF secretion. Constitutive phosphorylation of kinases and a diminished growth response to HGF suggest the presence of autocrine regulation in FH-OSE. In analogy with other cell types where an autocrine HGF-Met loop has been implicated in tumorigenic transformation, this change in FH-OSE may play a role in the enhanced susceptibility to ovarian carcinogenesis in women with hereditary ovarian cancer syndromes.
Autocrine Communication↗
Complete hydatidiform mole coexistent with a twin live fetus: clinical course of four cases with complete cytogenetic analysis.
Twin gestations can occur in which one twin is a normal gestation (46 chromosomes: 23 maternal and 23 paternal origin) and in which the other twin is a complete hydatidiform mole (46 chromosomes all of paternal origin). Case reports of four such combined pregnancies that presented to a single institution are provided. All cases had documentation of clinical information, cytogenetic analysis, and fetal and placental pathology. Three of the four pregnancies were terminated for medical indications despite information documenting the presence of a normal fetus. All three of these patients required subsequent chemotherapy. The fourth case was followed conservatively and resulted in the birth of a normal infant at 38 weeks gestation. We speculate that the factors that led to the need for termination of the pregnancy (aggressive growth of trophoblast) may predict the need for further therapy. A true assessment of the antenatal and malignant sequelae risks associated with these rare gestations awaits the collection of a larger series of patients.
Adult↗
Distinction of low grade from high grade human ovarian carcinomas on the basis of losses of heterozygosity on chromosomes 3, 6, and 11 and HER-2/neu gene amplification.
We examined the frequencies of loss of heterozygosity at 13 different loci distributed on 9 chromosomes in 30 human ovarian carcinomas. The same tumors were also examined for the presence of amplification of the HER-2/neu and H-ras protooncogenes. The results confirmed earlier findings that losses of heterozygosity occurred at nonrandom frequencies on chromosomes 3, 6, and 11 in these tumors. None of the tumors examined showed amplification at the H-ras locus. The HER-2/neu gene, however, was amplified in approximately one-third of the tumors, in agreement with earlier studies from other laboratories. We subdivided our tumor specimens according to their histological grades, which can be regarded as representing different stages of tumor progression. Losses of heterozygosity on chromosomes 3 or 11 were not seen in low grade lesions, although they were present in most of the high grade tumors examined. Losses of heterozygosity on chromosome 6 as well as HER-2/neu amplification, in contrast, were present in several low grade tumors and were not more frequent in high grade lesions. We conclude that the latter two abnormalities are associated with cellular functions involved at earlier stages of ovarian tumor development, whereas inactivation of genes on chromosome 3 or 11 is associated with later steps that may be incompatible with the well differentiated phenotype.
Animals↗
Loss of heterozygosity on chromosomal segments 3p, 6q and 11p in human ovarian carcinomas.
The genetic events involved in human ovarian carcinoma development are still largely unknown. We have used DNA recombinant technologies to examine the genome of normal and neoplastic tissues from 12 different patients with such tumors. We used cloned DNA sequences homologous to loci showing restriction fragment length polymorphisms on chromosomal segments 3p, 5p, 6q, 11p, or 21q to determine the frequencies of losses of constitutional heterozygosity at these loci in tumor DNAs. Losses affecting loci on 3p, 6q, and 11p were found in a high percentage of the cases examined. In contrast, losses of heterozygosity were not found when we used DNA probes for the other 2 above chromosomal segments. Thus, genetic losses involving chromosomal segments 3p, 6q and 11p occurred at non-random frequencies in ovarian carcinomas, suggesting that inactivation of genes located on these chromosomes played a role in their development.
Carcinoma↗
Detection of ras point mutations by polymerase chain reaction using mutation-specific, inosine-containing oligonucleotide primers.
The use of DNA primers with 3'-ends complementary to specific genetic point mutations allowed for the rapid detection of such mutations in genomic DNA by polymerase chain reaction. The sensitivity of this approach was such that mutations could be detected in DNA samples mixed with a 10(7)-fold excess of normal non-mutated DNA. To increase the practicality of this approach for the detection of point mutations affecting all 3 of the known ras oncogenes we synthesized mutation-specific primers complementary to all 3 genes by substituting inosine residues at positions corresponding to ambiguous bases on the genes.
Base Sequence↗
Posthysterectomy carcinoma of the fallopian tube presenting as vaginal adenocarcinoma: a case report.
The clinical and pathological features of a case of adenocarcinoma of the fallopian tube with a unique presentation are described. The 68-year-old patient presented with vaginal bleeding 25 years after a vaginal hysterectomy. Pelvic examination revealed a 0.5-cm nodule of tumor involving the mucosa of the vaginal apex. At laparoscopy, the left fallopian tube was dilated and adherent to the vaginal vault. Pathological examination of the upper vaginectomy and bilateral salpingo-oophorectomy specimen revealed a primary papillary adenocarcinoma of the left fallopian tube that had invaded directly into the mucosa of the vaginal apex. Vaginal involvement, either at the time of presentation or subsequently in the course of the disease, is very rare in patients with carcinoma of the fallopian tube.
Adenocarcinoma, Papillary↗
Isolation and characterization of the C3b-binding entity of C3b-receptor from human erythrocytes.
Applying 2 M KBr, membranes of Ehu were solubilized. By C3-affinity chromatography an activity could be isolated that inhibited the immune adherence reaction and C3b-dependent rosette formation. Since this material did not agglutinate EAC14oxy23b we termed it monovalent C3b receptor (mC3bR). PAGE and SDS-PAGE and staining with Coomassie brilliant blue and PAS reagent revealed a single glycoprotein band with a mol. wt. of 55,000-60,000 daltons and an electrophoretic mobility comparable to ovalbumin. This mC3bR proved to be antigenetically related to gp 205 [17]. The potential of mC3bR to react with C3b-carrying particles was not destroyed by heat and trypsin treatment but by neuraminidase or periodic acid treatment suggesting that mC3bR reacted by its carbohydrate moiety with C3b. As by mC3bR, immune adherence could be inhibited by D-glucose and D-galactose but not by their optical antipodes, L-glucose and L-galactose.
Animals↗
Differentiation of C3b receptors on human lymphocytes, phagocytes, erythrocytes and renal glomerulus cells by monoclonal antibodies.
C3b receptor protein was purified form human erythrocytes by 2 M KBr solubilization and affinity chromatography on C3-coated sepharose. This material served as antigen for raising monoclonal antibodies. To investigate the distribution and antigenetic relationship between the receptors for C3b on human erythrocytes, lymphoid and phagocytic cells, as well as kidney cells three monoclonal antibodies were selected which inhibited the binding of EAC14 degrees 23b to complement receptor-bearing cells. This could be shown for human erythrocytes by inhibiting the immune adherence reaction, for tonsil lymphocytes, Raji cells, and guinea-pig spleen cells by inhibition of rosette formation of these cells with EAC14 degrees 23b, and for human renal glomeruli by blocking of the the adherence of EAC14 degrees 23b to kidney sections. In contrast, these monoclonal antibodies were not capable of inhibiting rosette formation of human granulocytes and monocytes with EAC14 degrees 23b. The antibodies only interfered with the rosette formation, of EAC14 degrees 23bi and EAC14 degrees 23d with Raji cells and tonsil lymphocytes-if at all-at high concentrations, whereas the rosette formation of Raji cells and tonsil lymphocytes with EAC14 degrees 23b was influenced by supernatants of the selected clones up to a dilution of 1:10(3) to 1:10(5).
Animals↗
Description of a simple, specific, and sensitive test for the detection of detergent-solubilized C3b receptor.
The C3b receptor was isolated from detergent-solubilized human erythrocyte membranes by a previously described technique (1). The receptor glycoprotein was shown to enhance EAC14oxy23b rosette formation with Raji lymphoblastoid cells. This provided a specific and sensitive test to detect the solubilized C3b receptor either in crude or highly purified form. The property of the C3b receptor tested by this assay appears to be analogous to properties of beta 1H.
Burkitt Lymphoma↗