URINARY HCGB SUBUNIT/CORE FRAGMENT IN GYNECOLOGIC CANCER

妇科癌症中的尿液 HCGB 亚基/核心片段

• 批准号: 2092321
• 负责人: LAURENCE Anthony COLE
• 金额: $ 24.82万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1996-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2092321
• 关键词: biomarker; cervix neoplasms; chemoprevention; chorionic gonadotropin; diagnosis design /evaluation; diagnostic tests; female reproductive system neoplasm; high performance liquid chromatography; human subject; monoclonal antibody; neoplasm /cancer classification /staging; neoplasm /cancer immunodiagnosis; neoplasm /cancer relapse /recurrence; ovary neoplasms; radioimmunoassay; urine

Beta-Core fragment (synonyms: BetaCF, urinary gonadotropin fragment, UGF) is a small dimeric protein (Mr=10,300) composed of 2 short peptides (35 and 38 amino acids) linked by disulfide bridges. The two peptides each have sequence homology with segments of the Beta-subunit of hCG (145 amino acids). BetaCF can be detected by assays using BetaCF or hCGBeta antibodies in trophoblast/placenta tissue in pregnancy, and at relatively high levels in pregnancy urines, however, it cannot be detected by this means in blood. Thus, we initially selected urine samples for measuring BetaCF. In 1986-7 we found that hCG or its Beta-subunit were present in serum or urine of 18%, but BetaCF was present in the urine of 74%, of women with gynecologic cancers (n=68). Since then we have demonstrated with much larger populations, BetaCF is useful in monitoring the therapy of patients with gynecologic malignancies, and in the early detection of recurrent disease. BetaCF measurements are particularly useful in complementing plasma CA125 determinations. While CA125 is specific for epithelial carcinomas, BetaCF has equal sensitivity for this and other histologic subtypes. Urine BetaCF levels may also be useful in the differential diagnosis of benign disease and malignancy in patients presenting with a pelvic mass. Recently, many of these findings were confirmed, generally with larger populations, by independent laboratories. As a result of these and confirmatory studies, BetaCF is now being developed commercially and tested as a marker of gynecologic cancers, at centers in the U.S., U.K. and Japan. In this renewal we turn our attention to other yet-explored applications of BetaCF measurements: 1. To investigate the use of urinary BetaCF measurements in screening groups at high risk for ovarian cancer. 2. BetaCF is a secretory product of cancers, CA125 a membrane component sloughed-off dead cells. BetaCF, but not CA125, levels correlate with tumor grade, thus maybe indicative of cellular differentiation and chemistry. We propose investigating the use of BetaCF measurements in predicting the prognosis (mortality, persistence of disease, resistance to therapy) of ovarian cancers. 3. Preliminary studies suggest further uses for BetaCF in the diagnosis and management of breast and colon cancers (sensitivities 69% and 63%). Collaborative studies are proposed to evaluate these new applications. There has been some reluctance by physicians to use urine, rather than a plasma tumor markers. We asked ourselves "why can't BetaCF be detected in blood?". We considered the possibility that BetaCF is masked by associated molecules in serum. Studies using ammonium thiocyanate, a chaotropic agent, and gel filtration separation methods revealed this to be the case, and have now demonstrated the presence of BetaCF, as a specific BetaCF- macromolecule complex (Mr~65,000) in serum. Initial results are that this complex is present in all serum samples from women with pregnancy and form patients with gynecologic cancers with elevated parallel urine specimens (0.5-85 nmol/1, n=8). Initial indications are that serum measurements could replace, supplement or surpass (higher level detected in cancer serum) those of urine. We are currently trying to raise antibodies, and develop more-rapid HPLC methods for detecting the serum BetaCF complex. 4. We have parallel serum samples for most urines in our library. Wee propose, firstly, to establish the sensitivity and specificity of serum BetaCF complex measurements for gynecologic cancers (cancer samples n=300- 400, no evidence of disease and benign disease n=200-300), and then the efficacy in the differential diagnosis of benign and malignant disease, and in the management of therapy and detection of recurrences. Finally, to parallel Objectives 1, 2 and 3, described above, examining serum rather than urine samples and compare the utilities of serum and urine measurements.

β -核心片段（BetaCF，尿促性腺激素片段，UGF）