Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain cancer-associated substances are useful in the diagnosis and management of cancer. We have found that the estimation of serum alpha-fetoprotein and beta-human chorionic gonadotropin in patients with testicular tumors is useful. Of 17 patients with germ cell testicular tumors found to have elevated serum markers 3 had seminoma of the testis and all 3 had elevated beta-human chorionic gonadotropin. It is not possible, however, to correlate the histology of testicular tumors and the type of serum markers. All of our patients with elevated markers had active tumor. However, 3 patients with metastatic deposits in the para-aortic lymph nodes did not have elevated serum markers.
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PMID:Serum markers in testicular tumors. 8 96

Monoclonal or polyclonal antibodies to trophoblast components can be used to identify specific antigens. Such a vaccine will need to be effective before the completion of implantation and the appearance of the primitive streak about 14 days after fertilization. Monoclonal antibodies were evaluated at the Institute of Primate Research from WHO Panels and ones produced locally. Based on the results of placental reactivity, 12 antibodies were selected for further study and screened against selected baboon tissues. Monoclonal antibody T75 had the best specificity. A laparoscopic-guided uterine flush system was developed to replace the existing non surgical flush method in an effort to improve on the embryo recovery rate. Female baboons were introduced into the male cage for 5 hours/day for 6.3 +or- 3.4 days at stage 2, 3, or 4. 30 baboons were used in this study, but the animals were not flushed when bilateral adhesions were evident and the cervix or uterus could not be cannulated. Successful uterine flushed with immediate and complete return of the cultural medium were don in 20 animals. Superovulation of the baboons was tried to raise more embryos available for screening monoclonal antibodies. 4 animals were injected with human M gonadotropin (hMG) to stimulate follicular growth followed by human chorionic gonadotropin (hCG) to induce ovulation. Animals were mated following injection of hCG and laparoscopy was performed on day 6 of estimated pregnancy. Although follicular growth was evident, ovulation was not successful. Only 1 embryo was recovered from the 4 animals flushed. The recovered embryos were used for developing a cryosectioning technique to provide sections for screening monoclonal antibodies against pre implantation trophectoderm. Of the 8 baboon antibodies screened only 3 E7 showed reactivity against pre implantation baboon embryos.
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PMID:Anti-trophectoderm vaccines: rationale and methods used for antigen identification and selection. 151 28

The advances of both murine and human monoclonal antibody (MoAb) technology have allowed the development of several antibodies against gynecologic tumors. The goals are to produce effective and specific reagents for both immunodiagnosis and therapy. However, despite an extensive research effort, a clear demonstration of specific cancer-associated antigens in gynecologic malignancies, or of specific immune responses to such antigens has been elusive. Currently, most antibodies found are cross reactive with either oncofetal antigens or some normal adult tissues. Clinical usefulness of these MoAbs as a screening test in radioimaging or in immunotherapy remains to be proven. However, the use of MoAb technology in defined antigens/tumor markers such as beta-human chorionic gonadotropin, and alpha fetal proteins has provided convenient, reproducible and highly specific reagents. More recently, promising antibodies have been shown to detect tumor antigens in serum of patients with ovarian cancer.
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PMID:Clinical applications of monoclonal antibodies in gynecologic oncology. 330 66

We describe in this study a reliable method for the breeding of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Placing a male and a female WHHL rabbit in the same cage for the purpose of mating resulted in only two pregnancies out of a total of 227 mating attempts (0.9%). After manually assisting the rabbits, 15% of the matings resulted in pregnancies. When the female rabbits were injected with 40 I.U. of human chorionic gonadotropin within 1 hr of this procedure, 56% of the matings resulting in pregnancies. We feel that the inherent difficulty in breeding the WHHL rabbit, a model for the disease familial hypercholesterolemia, can be significantly overcome by the methods discussed in this report.
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PMID:Notes on the breeding of the WHHL rabbit: an animal model of familial hypercholesterolemia. 403 57

Aerobic microorganisms were isolated and identified from 9 of 10 malignant tissues aseptically obtained from surgical patients. The organisms isolated are species commonly associated with the flora of the human body. When these cancer-associated organisms were grown in Trypticase soy broth (BBL Microbiology Systems), a protein substance was isolated from the culture filtrates by acetone precipitation. The acetone precipitates of 12 of 14 organisms tested were positive when assayed by radioimmunoassay for the beta subunit of human chorionic gonadotropin (hCG). All but one of the bacterial isolates from the malignancies were capable of producing the hCG-like substance, but in varying quantities. Control organisms (not isolated from a malignancy) and uninoculated Trypticase soy broth were either completely negative in the radioimmunoassay for beta hCG or had levels of beta hCG near the limit of the sensitivity of the method. These results suggest the possibility that bacteria-tumor relationships do exist and are in agreement with the findings of other workers. Investigation of these relationships may have important and provocative implications in the study of neoplastic diseases.
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PMID:Tumor-associated bacteria capable of producing a human choriogonadotropin-like substance. 701 90

We have developed RNA molecules capable of effecting spliceosome-mediated RNA trans-splicing reactions with a target messenger RNA precursor (pre-mRNA). Targeted trans-splicing was demonstrated in a HeLa nuclear extract, cultured human cells, and H1299 human lung cancer tumors in athymic mice. Trans-splicing between a cancer-associated pre-mRNA encoding the beta-subunit of human chorionic gonadotropin gene 6 and pre-trans-splicing molecule (PTM) RNA was accurate both in vitro and in vivo. Comparison of targeted versus nontargeted trans-splicing revealed a moderate level of specificity, which was improved by the addition of an internal inverted repeat encompassing the PTM splice site. Competition between cis- and trans-splicing demonstrated that cis-splicing can be inhibited by trans-splicing. RNA repair in a splicing model of a nonfunctional lacZ transcript was effected in cells by a PTM, which restored significant beta-galactosidase activity. These observations suggest that spliceosome-mediated RNA trans-splicing may represent a general approach for reprogramming the sequence of targeted transcripts, providing a novel approach to gene therapy.
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PMID:Spliceosome-mediated RNA trans-splicing as a tool for gene therapy. 1009 82

Human chorionic gonadotropin (hCG), is a placental hormone which exerts its major effect by stimulating progesterone production, crucially sustaining the early weeks of pregnancy. Detection of hCG with specific monoclonal antibodies (mAbs) has become the chosen means for pregnancy diagnosis. We have used antibody Fv fragments derived from two high-affinity mAbs, one against the alpha and the other against the beta-hCG subunit to enable the crystallisation of intact or desialylated hCG. Crystals of a ternary complex composed of Fv anti-alpha/hCG/Fv anti-beta were found to diffract to 3.5 A resolution, and the structure was solved by molecular replacement. In the crystal, the two Fvs keep hCG as in a molecular cage, providing good protein-protein contacts and leaving enough space for the saccharides to be accommodated in the cell solvent. The two Fvs were found not to interact directly through their complementary-determining regions with the hCG saccharides, but only with the protein. The hCG structure in the ternary complex was very close to that of the HF partially deglycosylated hormone, thus indicating that neither the saccharides nor the Fvs had any substantial influence on hormone structure.
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PMID:Crystal structure of a ternary complex between human chorionic gonadotropin (hCG) and two Fv fragments specific for the alpha and beta-subunits. 1037 73

Nongestational choriocarcinomas are rare tumors. In the gastrointestinal tract, they are characterized by a biphasic tumor growth with separated areas of adenocarcinomatous and choriocarcinomatous differentiation. We here report a case of a combined adenocarcinoma-choriocarcinoma of the rectum. The tumor showed an aggressive clinical behavior with metastasis to the liver and lungs. A transient partial remission was achieved after 4 cycles of cisplatinum, etoposide, and ifosfamide chemotherapy, with normalization of serum beta-human chorionic gonadotropin levels. At this time, viable residual choriocarcinoma cells were found in surgically resected lung metastasis. The patient succumbed 8 months after initial diagnosis to a rapid abdominal relapse. We used comparative genomic hybridization (CGH) and fluorescence in situ hybridization to elucidate the genetic relationship of adenocarcinoma and choriocarcinoma in this neoplasm. We found genetic changes characteristic for colorectal adenocarcinomas, a loss of chromosomal regions 8p21-pter as well as 18q21-pter, and a gain of 5p and 20q, in both tumor parts. This provides evidence for the common origin of both components. A differential pattern of additional genetic changes suggests a clonal evolution from a common ancestor cell. In contrast to findings from a comparative study on a choriocarcinoma of the renal pelvis, we did not find an amplification of the germ cell cancer-associated chromosomal region 12p11.2-p12.1 in the areas of choriocarcinoma but found instead a loss of Xp11.3-pter. To our knowledge, this is the first report of a CGH comparison of the adenocarcinomatous and choriocarcinomatous tumor parts in a nongestational choriocarcinoma of the gastrointestinal tract.
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PMID:Rectal adenocarcinoma with choriocarcinomatous differentiation: clinical and genetic aspects. 1566 3

The tumor suppressor protein BARD1, originally discovered as BRCA1-binding protein, acts in conjunction with BRCA1 as ubiquitin ligase. BARD1 and BRCA1 form a stable heterodimer and dimerization, which is required for most tumor suppressor functions attributed to BRCA1. In addition, BARD1 has BRCA1-independent functions in apoptosis, and a role in control of tissue homeostasis was suggested. However, cancer-associated mutations of BARD1 are rare; on the contrary, overexpression of truncated BARD1 was found in breast and ovarian cancer and correlated with poor prognosis. Here we report that human cytotrophoblasts, which show a strong similarity with cancer cells in respect of their invasive behavior and capacity of matrix metalloprotease production, overexpress isoforms of BARD1 derived from differential splicing. We demonstrate that expression of BARD1 and its isoforms is temporally and spatially regulated by human chorionic gonadotropin and by hypoxia, both factors known to regulate the invasive phase and proliferation of cytotrophoblasts. Interestingly, we found a subset of BARD1 isoforms secreted by cytotrophoblasts. BARD1 repression by siRNAs, mitigates the interference of cytotrophoblasts with cell adhesion of collagen matrix-dependent epithelial cells, suggesting a role of BARD1 isoforms in extracellular matrix remodelling and in cytotrophoblasts invasion.
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PMID:Identification of BARD1 splice-isoforms involved in human trophoblast invasion. 1755 8

The purpose of the present study was to investigate the effects and underlying mechanism of gonadotropin-releasing hormone agonist (GnRHa) controlled ovarian hyperstimulation (COH) on embryo implantation in mice. Forty female Kunming mice aged 9 weeks were randomly divided into two groups (control and COH groups). The COH group received intraperitoneal (i.p.) injections of aminocyclin acetate (GnRHa), human menopausal gonadotropin (HMG) and human chorionic gonadotropin (hCG), while the control group was given equal amount of physiological saline by i.p. injection. One male mouse and two female mice were put into the same cage at 16:00 on the hCG injection day, and on the fourth day of pregnancy, 10 mice from each group were killed. The levels of serum estradiol (E2) and progesterone (P) were measured by radioimmunoassay; HE staining was used to observe the morphology of ovarian and endometrial tissues. The protein expression levels of endometrial leukemia inhibitory factor (LIF), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and glycodelin A were detected by Western blot and immunohistochemistry. Ten mice from each group were sacrificed on the eighth day of pregnancy, and the status of the uterus and the average number of blastocysts were observed. The results showed that, compared with control group, the serum E2 level in COH group was significantly decreased (P < 0.05), while the P level was increased significantly (P < 0.05); the ovarian follicles at different developmental stages were rare, corpus lutea (CL) were visible and multiple, the endometrium was thinned, and the number of endometrial glands was reduced (P < 0.05); the contents of LIF, p-STAT3, HB-EGF and glycodelin A in the endometrium were decreased significantly (P < 0.05) on the fourth day of pregnancy; mouse blastocysts developed slowly and were decreased in number on the eighth day of pregnancy (P < 0.05). The above results suggest that GnRHa COH can affect embryo implantation in mice. The mechanism may be related to the imbalance of gonadal hormone, the changes in the structure of the endometrium and the expressions of LIF, p-STAT3, HB-EGF and glycodelin A in the implantation stage, which may lead to the decrease of endometrial receptivity and the abnormal dialogue between the embryo and the uterus.
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PMID:[Effect of GnRHa controlled ovarian hyperstimulation on mouse embryo implantation and its mechanism]. 3037 87


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