ABSTRACT
Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate.
Subject(s)
Laboratories , Reference StandardsABSTRACT
A 43-year-old man with locally advanced squamous cell carcinoma of the base of tongue was treated with induction chemotherapy followed by intensity-modulated radiation therapy (IMRT). Within 20 days post-treatment, the patient developed clinical symptoms highly suggestive of hyperthyroidism. Two and one half months after completion of therapy, the patient developed severe thyrotoxicosis, which, in retrospect, appears to have met the criteria for thyroid storm. This case history illustrates a previously unreported, life-threatening complication of external-beam radiation that should be considered in patients receiving IMRT therapy involving the thyroid. Diagnosis of the patient's hyperthyroidism and probable thyroid storm was difficult to recognize because of the significant overlap between the signs and symptoms of severe thyrotoxicosis and the expected toxicities of his cancer therapy.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Radiation Injuries/etiology , Thyroid Crisis/etiology , Tongue Neoplasms/radiotherapy , Adult , Carcinoma, Squamous Cell/drug therapy , Combined Modality Therapy , Humans , Male , Radiotherapy, Intensity-Modulated/adverse effects , Thyroid Crisis/metabolism , Thyroid Hormones/metabolism , Tongue Neoplasms/drug therapyABSTRACT
In experiments with suspensions of cells from colonic carcinomas, we noted that some colonic carcinomas contain large numbers of eosinophils. We therefore carried out a prospective study with 67 almost consecutive colonic carcinomas in our medical center after optimal fixation and staining for the demonstration of eosinophils. Infiltration of the primary tumor by eosinophils was found to have marked prognostic significance. The proportion (4 of 17 or 23.5%) of carcinomas with more than 30 eosinophils/sq mm that had metastases was significantly less (p = 0.01) than the proportion (31 of 50 or 62.0%) of carcinomas with less than 30 eosinophils/sq mm that had metastases. At 18 months, following the resection of tumor in patients without metastases, all of the patients (9 of 9) with greater than 30 eosinophils/sq mm were alive in contrast to 73.7% (11 of 15) of the patients with less than 30 eosinophils/sq mm. The number of survivors at 18 months for the total population without regard to metastases was significantly greater (p = 0.028) for those with greater than 30 eosinophils/sq mm than for those with less than 30 eosinophils/sq mm. We conclude that the quantitative assessment of eosinophils is one of the most important aspects of the microscopic evaluation of this common human tumor.
