Disease relevance of NBR1

• The human NBR1 cDNA has previously been identified using polyclonal sera to CA125, an ovarian tumor antigen used in monitoring ovarian cancer [1].
• Expression of BRCA1, NBR1 and NBR2 genes in human breast cancer cells [2].
• RESULTS: Among 10 women with an elevated CA125 level and a positive TVU, three screening carcinomas (one FIGO stage IC, one stage IIIB and one stage IV) and one interval carcinoma (stage IV) were detected [3].
• Elevated levels of CA 125 were the harbinger in 2 of 7 cases of peritoneal serous papillary carcinoma, abnormal ultrasonographic findings prompted diagnosis in 2 of 7 cases, and 3 of 7 women had abdominal symptoms 5, 6, and 16 months after screening [4].
• A rising CA125 value prompted further (non-surgical) evaluation in three women with a history of breast cancer: recurrent breast cancer was diagnosed in two women; in the third, a chondrosarcoma was found [5].

Psychiatry related information on NBR1

• Of those who knew their mutation result, 11% underwent bilateral mastectomy (BM), 29% had bilateral oophorectomy (BO), 78% performed regular breast self-examination (BSE), and 80%, 89%, 67%, and 0% had at least annual clinical breast examination (CBE), mammography, transvaginal ultrasound (TVU), and CA125, respectively [6].
• Patients received twice annual physical examinations, imaging studies, measurement of CA125 and CA15-3, psychometric measurements, and unstructured interviews by a psychologist [7].
• CONCLUSION: Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy [8].
• More importantly, knowledge appeared to moderate the association between CA125 preoccupation and depressive symptoms [9].

High impact information on NBR1

• The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas [10].
• Re: Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer [11].
• Preoperative serum CA-125 levels in patients with surgical stage I invasive ovarian adenocarcinoma [12].
• CA125 is a normal epithelial-differentiation product of the oviduct, endometrium, and endocervix, but not of normal OSE [13].
• While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells [14].

Chemical compound and disease context of NBR1

• Among the 44 endometrial cancers, CA 125 HSCORE did not correlate with histological grade, depth of myometrial invasion or estrogen/progesterone receptor levels [15].
• The murine monoclonal antibody OC125 reacts with an antigenic determinant (CA 125) found on a high-molecular-weight glycoprotein complex present in the serum of greater than 80% of women with epithelial ovarian cancer [16].
• CONCLUSION: The GCIG CA-125 response criteria are a better prognostic tool than RECIST in second-line treatment with topotecan or paclitaxel plus carboplatin in patients with ovarian carcinoma [17].
• Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA125 [18].
• In one patient with ovarian cancer refractory to cisplatin, following two courses of quercetin (420 mg/m2), the CA 125 had fallen from 295 to 55 units/ml, and in another patient with hepatoma, the serum alpha-fetoprotein fell [19].

Biological context of NBR1

• The human BRCA1 and NBR2 genes and the homologous Brcal and Nbr1 mouse genes are situated head-to-head on human chromosome 17q21 and on mouse chromosome 11, respectively [2].
• Partial sequences of the 1A1-3B B-box protein pseudogene and IFP 35, an interferon induced leucine zipper protein, reside within the contig [20].
• We show that this region of the genome contains a tandem duplication of approximately 30 kilobases, which results in two copies of BRCA1 exons 1 and 2, of exons 1 and 3 of the adjacent 1A1-3B gene and of the previously reported 295 base pair intergenic region [21].
• Sequence analysis of the duplicated exons of BRCA1 and 1A1-3B and flanking genomic DNA reveals maintenance of the intron-exon structure and a high degree of nucleotide sequence identity, suggesting that these are non-processed pseudogenes and that the duplication is a recent event in evolutionary terms [21].
• We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation [22].

Anatomical context of NBR1

• By comparison of mRNA transcription in adult murine tissues and also in the mammary gland during pregnancy and lactation, we show that Brca1 and Nbr1 expression is coordinately regulated in a spatial and temporal manner to produce quite different patterns of expression, even from the same promoter [23].
• Thirty-seven cancers (84%) and 23 benign endometria (88%) expressed immunohistochemically detectable CA 125 [15].
• The three CA-125-negative cell lines, 2780, 2774, and HTB-77, did not respond to taxane treatment by expressing this tumor marker, although their proliferation was markedly inhibited [24].
• In addition, high CA 125 HSCORE also correlated with the presence of lymph node metastasis (P less than 0.001) [15].
• However, CA-125 concentration was increased in the supernatant medium only and not on cell surface or cytosol [24].

Associations of NBR1 with chemical compounds

• The scaffold protein NBR1 is involved in signal transmission downstream of the serine/protein kinase from the giant muscle protein titin [25].
• Since the OC 125 monoclonal antibody (Mab) was generated, other Mabs to the CA 125 glycoprotein have been produced and classified into two families associated with two major epitope regions on the CA 125 molecule [26].
• The addition of dexamethasone to gamma-interferon treated HTB-77 cells improved CA-125 expression synergistically [27].
• CA125 inhibition is also dependent on the concentration of steroid used, with half-maximal and maximal inhibition by dexamethasone occurring at about 3 x 10(-9) M and 1 x 10(-7) M, respectively [28].
• However, the change in CA-125 levels from before chemotherapy to 1 month later, after one course of carboplatin, could be used to divide patients into different prognostic groups [29].

Other interactions of NBR1

• The analysis of the murine and human syntenic region and its control has important implications for the regulation of human and murine BRCA1/NBR1 expression and the interpretation of animal models of disease [23].
• These data suggest that NBR1 may function, through interaction with CIB and FEZ1 in cell signalling pathways, with a developmentally restricted expression suggesting a possible role in neural development [30].
• We describe a new and detailed restriction map of the 5' region of the BRCA1 gene including the nearby NBR2, psiBRCA1, and NBR1 genes and the isolation of a number of new informative hybridization probes suitable for Southern analysis [31].
• Furthermore, p62 interacts both with MEK5 and NBR1 in addition to the aPKCs [32].
• Recently, the antigen CA125 has been cloned, and identified as a new mucin, MUC16, entirely different from NBR1 [30].

Analytical, diagnostic and therapeutic context of NBR1

• FEZ1 is highly expressed in the brain and in situ hybridization analysis of Nbr1 showed that its expression is also regulated in the murine brain during development [30].
• To determine the effectiveness of annual gynaecological screening (pelvic examination, transvaginal ultrasound, and CA-125), a prospective cohort study of women at high risk for hereditary ovarian cancer was conducted [33].
• We measured self-reported receipt of bilateral prophylactic oophorectomy (BPO) and utilization of CA-125 and transvaginal ultrasound (TVU) in the year following testing, and examined the impact of test results on these outcomes [34].
• The major contribution of CA 125 is in the monitoring of tumor response to chemotherapy, where it is valuable in detecting those patients with an inadequate response to the chosen treatment [26].
• The role of CA 125 in early detection of recurrences remains to be established and is currently the subject of two large clinical trials [26].

References