Background: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients.
Methods: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab.
Results: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029).
Conclusions: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.
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http://dx.doi.org/10.1186/s12885-022-09748-1 | DOI Listing |
Int J Mol Sci
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Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, 28922 Alcorcón, Madrid, Spain.
Clin Oral Implants Res
January 2025
Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
Objective: Abaloparatide (ABL) is a synthetic parathyroid hormone-related protein analog developed as an anabolic drug to treat osteoporosis. ABL increases bone mineral density (BMD) of the long bones and spine; however, the influence of ABL on alveolar bone regeneration remains unknown. This study assessed the effects of systemic ABL administration on tooth extraction socket healing and dental implant osseointegration in a preclinical rodent model.
View Article and Find Full Text PDFIntern Med
January 2025
Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo, Japan.
Methotrexate-associated lymphoproliferative disorder (MTX-LPD) constitutes a subset of lymphoid proliferations and lymphomas that are associated with immune deficiency and dysregulation. The clinical management of MTX-LPDs is contingent on their histopathological subtypes. Polatuzumab vedotin is a novel therapeutic approach that is particularly beneficial for selecting patients with previously untreated diffuse large B-cell lymphoma (DLBCL); however, DLBCL-type MTX-LPD is still treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) because of the exclusion of MTX-LPD from clinical trials.
View Article and Find Full Text PDFCell Biosci
December 2024
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, USA.
Mammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. Meeting this demand requires the activation of a brain-breast-bone circuit during lactation that coordinates changes in systemic hormones, dietary calcium intake, skeletal turnover, and calcium transport into milk. Classically, increased bone resorption via increased parathyroid hormone-related protein and low estrogen levels is the main source of calcium for milk production during lactation.
View Article and Find Full Text PDFOsteoarthritis Cartilage
December 2024
Department of Oral Anatomy and Physiology and TMD, College of Stomatology, the Fourth Military Medical University, Xi'an, China; Department of Oral Anatomy and Physiology and TMD, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China. Electronic address:
Objective: Some cells in temporomandibular joint (TMJ) cartilage undergo proliferation in response to negative pressure, which can be induced in vivo by creating bilateral anterior elevation (BAE). TMJ cartilage harbours CD90-expressing cells, and CD90 expression increases under certain controlled conditions. The parathyroid hormone-related peptide (PTHrP) nuclear localisation segment (NLS) promotes chondrocyte proliferation, and mammalian target of rapamycin (mTOR) signalling plays a regulatory role in promoting PTHrP transcription.
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