{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:53:28Z","timestamp":1761512008807,"version":"build-2065373602"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2004,10,29]],"date-time":"2004-10-29T00:00:00Z","timestamp":1099008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Parathyroid hormone\u2013related protein (PTHrP) expression modulates cell survival in a number of human solid tumors. Although PTHrP is expressed in normal developing and neoplastic central nervous system tissue, clinical data indicating the importance of this protein with respect to local control and\/or survival in patients with glial tumors are scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Using a standard immunoperoxidase technique, the authors examined PTHrP expression in a population of 51 patients with Daumas\u2013Duport Grade II\u2013IV astrocytomas over a 15\u2010year period. Both local control and survival were calculated from the date of definitive irradiation to the last time of known follow\u2010up examination using the actuarial method. PTHrP expression was scored on examination under 40\u00d7 magnification, with the incidence of cellular staining averaged over 10 high\u2010power fields. The intensity and extent of staining were characterized semiquantitatively using the standard World Health Organization classification criteria. The median follow\u2010up duration was approximately 5.5 years. Multivariate analyses were performed to ascertain the statistical significance of several standard clinicohistopatholgic factors (Karnofsky functional status, age, gender, extent of surgical resection, radiotherapy dose, grade, and PTHrP expression) with respect to local control and survival. <jats:italic>P<\/jats:italic> &lt; 0.05 was considered indicative of statistical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Patients with high levels of PTHrP expression had significantly lower glial tumor local control rates and corresponding decreases in progression\u2010free and overall actuarial survival after definitive irradiation (<jats:italic>P<\/jats:italic> &lt; 0.01). In a Cox 3\u2010variable model, the PTHrP staining score was independent of tumor grade or Karnofsky functional status. It is notable that the strongest predictor of survival was tumor grade (<jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>PTHrP may be an important adjunct to standard immunopathologic criteria in the determination of glial tumor responses. A number of mechanisms were explored to derive a more mechanistic understanding of these translational results. Subsequent prospective studies involving larger patient populations will be necessary before findings can be translated to clinical practice. Cancer 2004. \u00a9 2004 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.20689","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T19:32:38Z","timestamp":1100287958000},"page":"2622-2628","source":"Crossref","is-referenced-by-count":10,"title":["Parathyroid hormone\u2013related protein expression is correlated with clinical course in patients with glial tumors"],"prefix":"10.1002","volume":"101","author":[{"given":"Francisco S.","family":"Pardo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winston W.","family":"Lien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard S.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy T.","family":"Efird","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Aguilera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas W.","family":"Burton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard J.","family":"Deftos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1155\/2002\/651582","article-title":"Severe hypercalcemia as an initial presenting manifestation of hepatocellular carcinoma","volume":"16","author":"Ghobrial MW","year":"2002","journal-title":"Can J Gastroenterol."},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.271.2.E277"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00489.2002"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3616618"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001527r"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.142.9.4096"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1161085"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-133X(02)00074-1"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(02)00685-3"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0211936"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00078.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.49.335"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2003.02939.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2003.05171.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.3.C691"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0150245"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.8.2841"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02934499"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711750211"},{"key":"e_1_2_6_21_2","first-page":"77","article-title":"Antisense inhibition of parathyroid hormone\u2010related peptide gene expression reduces malignant pituitary tumor progression and metastases in the rat","volume":"56","author":"Akino K","year":"1996","journal-title":"Cancer Res."},{"key":"e_1_2_6_22_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00428-002-0743-5","article-title":"Prognostic value of immunocytochemical determination of parathyroid hormone\u2010related peptide expression in cells of mammary ductal carcinoma. 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