Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00428597.).

Cross-linked dextran (Sephadex) has been reported as an effective inducer of peritoneal exudates resulting in a large yield of macrophages after injection into mice, and macrophages obtained in this manner have been used for a variety of studies. We examined the possibility that cross-linked dextran not only induces peritoneal exudate but functions also as a macrophage activator. Following confirmation of a markedly increased yield of macrophages in Balb/c mice injected with preswollen Sephadex G-25 beads, glass adherence and migration in agarose of these macrophages were compared with the activities of cells isolated following the injection of saline, thioglycollate, or complete Freund's adjuvant (CFA). Dextran administration resulted in a significant increase in these activities in relation to saline and thioglycollate injections, and resembled CFA in the magnitude of its effect. Dextran-induced macrophages were then examined for activation as defined by nonspecific antitumor activity. Cells of a transplantable fibrosarcoma line and a urethane-induced primary lung adenoma served as targets. As compared with macrophages isolated from saline-injected mice, cells induced by Sephadex showed an approximately fivefold and twofold increase in activity against adenoma and fibrosarcoma targets, respectively. To examine the ability of Sephadex to induce macrophage antitumor activity in vitro, peritoneal macrophages were cultured in the presence of the dextran for 24 hours and tested against adenoma targets. The tumoricidal/static activity of such macrophages was significantly increased relative to controls and was nearly identical to the activity of macrophages induced by Sephadex in vivo. It is clear that cross-linked dextran in the form of Sephadex G-25 can function both as an inducer of peritoneal exudate and as an effective macrophage activator with regard to the activation criteria studied.

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Background: ALK rearrangement and EGFR mutation are significant molecular subtypes of non-small cell lung cancer (NSCLC) that are targets for different tyrosine kinase inhibitors (TKIs). We tested a large cohort of NSCLC patients for ALK, EGFR and KRAS abnormalities and correlated clinical factors with the ALK fusion gene and overall survival (OS). Methods: ALK status was detected by RACE sequencing; EGFR and KRAS status were also detected by direct DNA sequencing. OS was estimated by the Kaplan-Meier method. Results: 294 consecutive, unselected, banked NSCLC cases were tested; 27 (9.2%), 79 (29.2%) and 26 (9.6%) patients were ALK-, EGFR- and KRAS-positive, respectively. ALK rearrangement and EGFR mutation were largely exclusive (r=−0.15, P=0.007) although two cases were both ALK- and EGFR-positive. In non-parametric tests, ALK-positivity was associated with female gender (χ2=5.189; P=0.023), non/light-smoking (χ2=6.067; P=0.014) and adenocarcinoma (χ2=4.301; P=0.038). The ALK fusion partner was EML4 in all 27 cases; EML4-ALK fusion variants V1, V2 and V3 (V3a/V3b/V3c) made up the majority (24/27) of EML4-ALK fusions. There were no significant OS differences between ALK-positive, EGFR-mutant, KRAS-mutant and triple-negative groups, between ALK-positive and -negative patients, or when ALK-positive cases were matched 1:2 or 1:1 with (non-TKI-treated) controls balancing for disease stage, gender, histology and EGFR/KRAS status. In ALK-positive patients, bivariate analysis found that non- or light-smoking status (P=0.016) and prior surgery (P=0.024) were associated with increased OS and a multivariate Cox regression model found that disease stage and surgical treatment were prognostic for OS. In a multivariate logistic regression model, female gender (HR=2.793; P=0.041), wild type EGFR (HR=15.147; P=0.001), non/light-smoking (HR=3.572; P=0.020) and adenocarcinoma (HR=5.713; P=0.024) were significantly associated with ALK-rearrangement. Conclusion: Overall, the ALK fusion gene occurred in 9.2% of NSCLC patients, and was associated with non/light-smoking history, adenocarcinoma histology and female gender. ALK fusion variants were mostly V1-3, which may inform ALK screening by RT-PCR. ALK rearrangement was not a favorable prognostic factor in NSCLC, although smoking history may influence OS in ALK-positive patients. A TKI (crizotinib) now exists for ALK-positive NSCLC and may improve OS in these patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4504. doi:1538-7445.AM2012-4504

Since their discovery in 1971 (1, 2), T suppressor (Ts) ~ cells have been the object of numerous studies. Particularly helpful in the characterization of Ts cells was the establishment of cloned T cell lines, such as T cell hybridomas, long-term T cell lines, or transformed T cells (for a survey see 3). A surprisingly large number of Ts subpopulations have been distinguished. Ts and suppressor factors (TsF) derived from them belong either to the inducing arm of the suppressor circuit or to the effector arm that ultimately mediates suppression. They appear to be either antigen specific or nonspecific, H-2 restricted, and heavy chain variable region (VH) restricted or nonrestricted (reviewed in 4-6). Recent advances (7-17) in the molecular and genetic characterization of antigenspecific receptors of T cells, consisting of two chains, a and ~8, have not only revealed some degree of homology to immunoglobulin but also a basic similarity of receptors on T helper cells (Th) and cytotoxic T iymphocytes (Tc). In contrast, the nature of the antigen receptors on Ts remains elusive. The rearrangement of/3 chain genes described for Th and Tc have not been observed in most antigen-specific Ts cells (18), suggesting that the receptor molecule of the Ts cell is unique. However, none of the murine Ts cells that have been investigated for rearrangement were class II or class I major histocompatibility complex (MHC) restricted, as were the Th and Tc lines, respectively.In the present report we describe the establishment and functional characterization of Ts hybridomas that are antigen specific and I-A restricted. In this respect the Ts hybridomas are similar to Th cells.

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