We recently generated an HT-1080-derived cell line called HT-AR1 that responds to dihydrotestosterone (DHT) treatment by undergoing cell growth arrest in association with cytoskeletal reorganization and induction of neuroendocrine-like cell differentiation. In this report, we show that DHT induces a dose-dependent increase in G 0 /G 1 growth-arrested cells using physiological levels of hormone. The arrested cells increase in cell size and contain a dramatic redistribution of desmoplakin, keratin 5, and chromogranin A proteins. DHTinduced cytoskeletal changes were also apparent from time lapse video microscopy that showed that androgen treatment resulted in the rapid appearance of neuronallike membrane extensions. Expression profiling analysis using RNA isolated from DHT-treated HT-AR1 cells revealed that androgen receptor activation leads to the coordinate expression of numerous cell signaling genes including RhoB, PTGF-␤, caveolin-2, Egr-1, myosin 1B, and EHM2. Because RhoB has been shown to have a role in tumor suppression and neuronal differentiation in other cell types, we investigated RhoB signaling functions in the HT-AR1 steroid response. We found that steroid induction of RhoB was DHT-specific and that newly synthesized RhoB protein was post-translationally modified and localized to endocytic vesicles. Moreover, treatment with a farnesyl transferase inhibitor reduced DHT-dependent growth arrest, suggesting that prenylated RhoB might function to inhibit HT-AR1 cell proliferation. This was directly shown by transfecting HT-AR1 cells with RhoB coding sequences containing activating or dominant negative mutations.

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In this study, small (outside diameter 1 mm) cylindrical ultrasound sources were investigated for induction of hyperthermia in tumours. These ultrasound transducers could be placed in small-diameter body cavities, or they could be used interstitially in brachytherapy catheters. The ultrasound field measurements showed that the field is fairly uniform as a function of the length of the applicator except at the ends where sharp peaks were located. However, there were significant field variations as a function of rotation angle around the transducers. The degree of these non-uniformities varied from transducer to transducer, and also as a function of frequency. The temperature measurements in vitro perfused kidneys showed that therapeutic temperature elevations could be induced in perfused tissues. The radial extent of the therapeutic zone could be increased by circulating water around the applicators, thus avoiding high temperatures on the applicator surface. It was also shown that some control over the temperature distribution along the length of the applicator could be achieved by using a two-element applicator. An array of four applicators implanted in a square pattern with the spacing of 25 mm between the catheters, was able to heat the tissue volume inside of the implant. The results showed that these small ultrasound applicators may offer significant improvement over existing techniques by increasing the penetration depth and the control over the power deposition pattern.

Herpes esophagitis due to infection with herpes simplex virus typically occurs in immunocompromised patients such as those with human immunodeficiency virus, malignancy, and those undergoing immunosuppressive therapy. Albeit rare, herpes esophagitis can occur in immunocompetent patients as a primary infection. We present a case of herpes esophagitis after corticosteroid treatment for back pain including epidural steroid injections. Corticosteroids, especially local injections, are a common treatment for chronic back pain, but they are not without risk. Epidural steroid injections can have systemic effects, which may go unrecognized and underappreciated. Although local infections have been reported after administering these injections, systemic immune suppression may allow for unexpected infections such as herpes esophagitis. Given the widespread use of epidural steroid injections, physicians should reevaluate the potential for harm when considering this treatment.

Immune focused interventions remain a high priority for many drug discovery efforts, spurred on by the success of immune checkpoint therapies such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 inhibitory antibodies. Preclinical efficacy assessments of novel immune-oncology therapies requires a functional immune system which limits the usefulness of traditional xenograft models and drive the use of humanized (human immune cell engrafted animals) and syngeneic model systems. Syngeneic mouse tumors are popular model systems in which to evaluate these novel therapies due the presence of fully intact mouse immune system and ease of accessibility. The MC38 mouse colon cancer model is popular for efficacy assessment studies due to its responsiveness to typical immune checkpoint inhibitors. We endeavored to characterize the immune response to checkpoint inhibitors in MC38 tumors using flow cytometry, gene expression analysis, and immunohistochemistry (IHC). Gene expression analysis provided a signature of gene changes that correlate to immune driven changes in tumor growth and may be used in preclinical pharmacodynamics studies as evidence of mode of action for other novel immune-oncology therapies. In addition, gene overrepresentation analysis highlighted the presence and involvement of B cell populations in the MC38 tumor environment which was supported by IHC data that show distinctive B cell staining in what resemble tumor associated tertiary lymph structures. These finding suggests that MC38 may provide a good model system for evaluating therapies that can modulate or impact tumor infiltrating B cell populations. Citation Format: Patrick Fadden, Thi Bui, David Hurtado, Kelli Davis, Ian Belle, Kathrine Krontz, Jacob Hauser, Na Li, Kyle Takayama, Cristina Sokolowski, Edgar Wood. Characterization of the immune checkpoint inhibitor response in the MC38 murine colon cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-060.