URINARY HCGB SUBUNIT/CORE FRAGMENT IN GYNECOLOGIC CANCER

β-核心片段（同义词：BetaCF，尿促性腺激素片段，UGF） 是一种小的二聚体蛋白质（Mr = 10，300），由2个短肽（35和36）组成。 38个氨基酸）通过二硫键连接。 这两种肽各自具有 与hCG β-亚基片段（145个氨基酸）的序列同源性 酸）。 可通过使用BetaCF或hCG β的测定来检测BetaCF 妊娠期滋养层/胎盘组织中的抗体， 怀孕尿液中的高水平，然而，它不能被检测到， 意味着血。 因此，我们最初选择尿液样本进行测量， BetaCF。 1986 - 1987年，我们发现hCG或其β亚单位存在于 18%的女性血清或尿液中存在β CF，但74%的女性尿液中存在β CF。 妇科癌症（n = 68）。 从那时起，我们已经证明了很多 在更大的人群中，BetaCF可用于监测患者的治疗 妇科恶性肿瘤，并在早期发现复发 疾病 BetaCF测量在补充 血浆CA 125测定。 虽然CA125对上皮细胞具有特异性， BetaCF对这种癌和其他组织学癌具有相同的敏感性， 亚型 尿BetaCF水平也可能有助于鉴别 诊断良性疾病和恶性疾病的患者提出了一个 盆腔肿块 最近，这些发现中有许多得到了证实， 通过独立的实验室， 由于这些 和验证性研究，BetaCF目前正在商业化开发， 作为妇科癌症的标志物，在美国的中心进行了测试，英国和 日本 在这次更新中，我们将注意力转向其他尚未探索的 BetaCF测量的应用： 1. 研究尿BetaCF测量在筛查中的应用 卵巢癌的高危人群 2. BetaCF是癌症的分泌产物，CA 125是膜组分 脱落的死细胞 BetaCF，而不是CA125，水平与 肿瘤分级，因此可能指示细胞分化， 化学. 我们建议调查BetaCF测量在以下方面的使用： 预测预后（死亡率、疾病的持续性、对 治疗）卵巢癌。 3. 初步研究表明BetaCF在诊断中的进一步用途 乳腺癌和结肠癌的治疗（敏感性分别为69%和63%）。 建议进行合作研究，以评估这些新的应用。 医生们不太愿意使用尿液，而不是 血浆肿瘤标志物 我们问自己"为什么BetaCF不能在 血吗". 我们考虑了BetaCF被相关的 血清中的分子 研究使用硫氰酸铵， 试剂和凝胶过滤分离方法揭示了这种情况， 现在已经证明了BetaCF的存在，作为一种特定的BetaCF- 血清中大分子复合物（Mr~65，000）。 初步结果显示， 复合物存在于所有血清样品从妇女怀孕和形式 平行尿标本升高的妇科癌症患者 （0.5 - 85 nmol/l，n = 8）。 初步迹象表明，血清测量 可以取代、补充或超过（在癌症中检测到的较高水平） 血清）尿的那些。 我们目前正在努力提高抗体， 开发更快速的HPLC方法检测血清BetaCF复合物。 4. 在我们的图书馆里有大多数尿液的平行血清样本。 wee 建议首先建立血清的敏感性和特异性， 用于妇科癌症的BetaCF复合测量（癌症样品n = 300 - 200）。 400，无疾病证据和良性疾病n = 200 - 300），然后 在良性和恶性疾病的鉴别诊断中的功效，以及 在治疗管理和复发检测方面。 最后为 平行目标1、2和3，如上所述，检查血清，而不是 并比较血清和尿液的效用 测量.

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.