PubMed · 14928457
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H BARTELHEIMER. 1951. [Present endocrinologic problems].. https://pubmed.ncbi.nlm.nih.gov/14928457/
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Despite multimodality treatment for thyroid cancer, including surgical resection, radioiodine therapy, thyrotropin (TSH)-suppressive thyroxine treatment, and chemotherapy/radiotherapy, survival rates have not improved over the last decades. Therefore, development and evaluation of novel treatment strategies, including gene therapy, are urgently needed. A variety of gene therapy approaches have been evaluated for the treatment of follicular cell-derived and medullary thyroid cancer, including corrective gene therapy (p53 restoration, expression of a dominant negative RET mutant), cytoreductive gene therapy (suicide gene/prodrug strategy herpes simplex virus-thymidine kinase [HSV-tk]/ganciclovir, antiangiogenic therapy with endostatin) and immunomodulatory gene therapy (expression of interleukin (IL)-2 and IL-12). Furthermore, cloning of the sodium iodide symporter (NIS) gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on NIS gene transfer followed by the application of radioiodine therapy ((131)I). NIS gene delivery into medullary and follicular cell-derived thyroid cancer cells has been shown to be capable of establishing or restoring radioiodine accumulation and might therefore represent an effective therapy for medullary and dedifferentiated thyroid tumors that lack iodide accumulating activity. The data summarized in this review article clearly demonstrate that the currently available strategies represent potentially curative novel therapeutic approaches for future gene therapy of thyroid cancer. The combination of different therapeutic genes has been demonstrated to be very useful to enhance therapeutic efficacy and seems to have a promising role at least as part of a multimodality approach for advanced thyroid cancer.
Proteomics is the comprehensive and systematic study of proteins, which are functional molecules. Although proteins are products of gene expression, there are more proteins than genes due to the posttranslational modifications of proteins, making the study of proteins difficult. Protein expression is tissue specific, and its function is modulated by variety of factors, including other proteins, phosphates, sulfates, carbohydrates, and lipids, as well as other metabolites. Because of the dynamic nature of protein expression and posttranslational modifications, identification and quantification of proteins alone are not sufficient to understand functional changes. Emerging technologies will allow investigators to perform a combination of metabolic labeling and identification as well as quantification and measurement of the synthesis rates of a large number of proteins in a tissue. This offers the opportunity to better understand the regulation of tissue functions. Rapid advances in mass spectrometry, protein purification techniques, isotope labeling of proteins, and bioinformatics are likely to improve our understanding of physiological states and altered functions in diseased states. Such mechanistic information will improve the ability to perform early diagnosis of tumors and other diseases and develop prognostic indexes and novel therapies.
BACKGROUND: Minimally-invasive parathyroidectomy (MIP) appears to be changing preoperative treatment and referral patterns for sporadic, nonfamilial, non-multiple endocrine neoplasia, primary hyperparathyroidism (PHPT). METHODS: The American Association of Clinical Endocrinologists membership was surveyed by mail (n=1406 members) regarding physician practices and surgical referral patterns for PHPT. RESULTS: Seven hundred eighty-eight respondents (56%) practiced 17.0+/-0.4 years and referred 63%+/-1% of patients with PHPT for operation. Most endocrinologists (90%) used localizing studies before surgical referral (sestamibi, ultrasound scanning, technetium/thallium scanning, magnetic resonance imaging, computed tomography). Respondents identified symptoms, calcium homeostasis, bone density, health status, age, and general anesthesia risk as the most important considerations for surgical referral. Most respondents (79%) indicated that MIP availability would increase the number of patients who were referred for operation (P<.001), although most of the respondents stated that MIP would change the extent and duration of preoperative evaluations (P<.001). Respondents in practice for fewer years were more likely to refer patients for MIP (P<.001) and minimize preoperative evaluation (P<.05). Endocrinologists who had a patient with a complication after traditional parathyroidectomy were more likely to embrace MIP (P<.05). CONCLUSIONS: MIP availability decreases the extent and duration of preoperative evaluation while decreasing the time from diagnosis to referral. MIP also lowers the endocrinologists' surgical referral threshold for PHPT, although it emphasizes the perceived shortcomings of traditional parathyroidectomy that are held by many physicians.