A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.

We have cloned and characterized a human gene encoding TP2 (telomerase-associated protein 2), a protein with similarity to reverse transcriptases and the catalytic telomerase subunits from Saccharomyces cerevisiae and Euplotes aediculatus. Indirect immunofluorescence revealed that TP2 was localized to the nucleus. Using antibodies to endogenous and epitope-tagged TP2, we found that TP2 was associated specifically with human telomerase activity and the recently identified telomerase-associated protein TP1. Mutation of conserved residues within the reverse transcriptase domain of TP2 severely reduced associated telomerase activity. These results suggest that telomerase is an evolutionarily conserved multisubunit complex composed of both structural and catalytic subunits.

Investigators using anti-EpoR antibodies for immunoblotting and immunostaining have reported erythropoietin receptor (EpoR) expression in nonhematopoietic tissues including human tumors. However, these antibodies detected proteins of 66 to 78 kDa, significantly larger than the predicted molecular weight of EpoR (56-57 kDa). We investigated the specificity of these antibodies and showed that they all detected non-EpoR proteins. C-20 detected 3 proteins in tumor cell lines (35, 66, and 100 kDa). Sequences obtained from preparative gels had similarity to the C-20-immunizing peptide. The 66-kDa protein was a heat shock protein (HSP70) to which antibody binding was abrogated in peptide competition experiments. Antibody M-20 readily identified a 59-kDa EpoR protein. However, neither M-20 nor C-20 was suitable for detection of EpoR using immunohistochemical methods. We concluded that these antibodies have limited utility for detecting EpoR. Thus, reports of EpoR expression in tumor cells using these antibodies should be viewed with caution. (Blood.

Background Supportive oncology practice can be enhanced by integrating brief and validated electronic patient-reported outcome (ePRO) assessment into the electronic health record (EHR) and clinical workflow. Methods 636 women receiving gynecologic oncology outpatient care received instructions to complete clinical assessments through Epic MyChart, the EHR patient communication portal. PROMIS computer adaptive tests (CATs) were administered to assess fatigue, pain interference, physical function, depression, and anxiety. Checklists identified psychosocial concerns, informational and nutritional needs, and risk factors for inadequate nutrition. Assessment results, including PROMIS T-scores with documented severity thresholds, were immediately populated in the EHR. Clinicians were notified of clinically elevated symptoms through EHR messages. EHR integration was designed to provide automated triage to social work providers for psychosocial concerns, health educators for information, and dietitians for nutrition-related concerns. Results Of 4,042 MyChart messages sent, 3,203 (79%) were reviewed by patients. The assessment was started by 1,493 (37%) patients, and once started 93% completed (1,386 patients). Using first assessments only, 49.8% of patients who reviewed the MyChart message completed the assessment. Mean PROMIS CAT T-scores indicated a lower level of physical function and elevated anxiety compared to the general population. Fatigue, pain, and depression scores were comparable to the general population. Impaired physical functioning was the most common basis for clinical alerts, occurring in 4% of patients. Conclusions We used PROMIS CATs to measure common cancer symptoms in routine oncology outpatient care. Immediate EHR integration facilitated the use of symptom reporting as the basis for referral to psychosocial and supportive care.