No abstract

This report concerns a 79-year-old woman with coexisting anaplastic thyroid carcinoma (ATC) and Graves' disease (GD). The patient was referred to our clinic because of palpitation and a palpable mass on the left side of her neck. Thyroid function tests showed hyperthyroidism with elevated thyroid-stimulating antibodies. Ultrasonography of the thyroid demonstrated an adenomatous nodule-like marcated nodule (27.6 x 26.5 x 36.4 mm) with cystic degeneration inside the left lobe. (123)I thyroid scintigraphic imaging showed a cold area corresponding to the nodule with continuous uptake in the remaining thyroid tissue despite suppressed TSH levels. These findings led to a diagnosis of GD. On the other hand, the thyroid nodule could not be definitely diagnosed even after fine needle aspiration biopsy (FNAB) which produced findings suggestive of both papillary thyroid carcinoma and ATC. Open biopsy of the nodule showed an ATC. Regional lymph node metastases as well as multiple lung metastases, which could not be found at the initial visit, had been already developed by that time. Our case is pathophysiologically interesting because it suggests that GD or thyroid-stimulating antibodies (TSAb) may stimulate malignant transformation of differentiated carcinoma. It is also clinically important because it indicates that all thyroid nodules, particularly palpable cold nodules, associated with GD require careful management to detect malignancy because they are at higher risk of harboring malignancy.

No abstract

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8 T-cells, co-cultured with a tumor-specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8 T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8 T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8 T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8 T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo.

No abstract