Faculty Bibliography

Toxoplasma gondii transmission between intermediate hosts is dependent on the ingestion of walled cysts formed during the chronic phase of infection. Immediately following consumption, the parasite must ensure survival of the host by preventing adverse inflammatory responses and/or by limiting its own replication. Since the Toxoplasma secreted effectors rhoptry 16 kinase (ROP16) and dense granule 15 (GRA15) activate the JAK-STAT3/6 and NF-kappaB signaling pathways, respectively, we explored whether a particular combination of these effectors impacted intestinal inflammation and parasite survival in vivo. Here we report that expression of the STAT-activating version of ROP16 in the type II strain (strain II+ROP16I) promotes host resistance to oral infection only in the context of endogenous GRA15 expression. Protection was characterized by a lower intestinal parasite burden and dampened inflammation. Host resistance to the II+ROP16I strain occurred independently of STAT6 and the T cell coinhibitory receptors B7-DC and B7-H1, two receptors that are upregulated by ROP16. In addition, coexpression of ROP16 and GRA15 enhanced parasite susceptibility within tumor necrosis factor alpha/gamma interferon-stimulated macrophages in a STAT3/6-independent manner. Transcriptional profiling of infected STAT3- and STAT6-deficient macrophages and parasitized Peyer's patches from mice orally challenged with strain II+ROP16I suggested that ROP16 activated STAT5 to modulate host gene expression. Consistent with this supposition, the ROP16 kinase induced the sustained phosphorylation and nuclear localization of STAT5 in Toxoplasma-infected cells. In summary, only the combined expression of both GRA15 and ROP16 promoted host resistance to acute oral infection, and Toxoplasma may possibly target the STAT5 signaling pathway to generate protective immunity in the gut.

BACKGROUND: Sarcomatoid salivary duct carcinoma of the submandibular gland is extremely rare. This paper highlights the impact of surgery and adjuvant radiation therapy on the outcome of this disease. METHODS: A 59-year-old man with human immunodeficiency virus presented with a painless, rapidly growing left neck mass. Biopsy followed by surgical excision of the left submandibular gland revealed sarcomatoid salivary duct carcinoma of the submandibular gland duct with perineural invasion and close margins, for which he underwent adjuvant radiotherapy. Post-operative positron emission tomography and computed tomography revealed no residual or metastatic disease. Pathological analysis of tumour-node-metastasis staging revealed a T2 N0 M0 (stage II) tumour. RESULTS: The patient tolerated his treatment without serious acute or long-term side effects. There was no evidence of disease on comprehensive examination or on positron emission tomography or computed tomography scans at the 4.6-year follow up. CONCLUSION: Surgery followed by adjuvant radiotherapy provided practical locoregional control with acceptable toxicity. Further detailed case reports are warranted to optimise the management of this rare malignancy.

OBJECTIVES/HYPOTHESIS: To report tolerance and toxicity of radiotherapy (RT) with or without chemotherapy in HIV seropositive patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: This is a single institution retrospective study of 73 HIV seropositive patients with SCCHN treated from January 1997 through 2010. Stages I, II, III, and IV were 8%, 10%, 24%, and 58%, respectively. The median age at RT, HIV diagnosis. and the duration of HIV seropositive were 51 (32-72), 34 (25-50), and 11 (6-20) years, respectively. Patients were treated definitively with RT alone (35%) or concurrent chemo-RT (65%). Median dose of 70 Gy (66-70) was delivered to the gross disease. Median duration of treatment was 52 (49-64) days. Fifty patients (70%) were on HAART. RESULTS: RT+/- chemotherapy induced acute toxicity was: median weight loss 20 pounds (6-40), 100% developed dysgeusia and xerostomia (grades 1-3). Acute mucositis and dysphagia/odynophagia grades 2 were 26% and 23% of patients, respectively. CONCLUSION: Our data show that primary RT +/-chemotherapy for HIV seropositive SCCHN is less tolerated compared to the historical data for SCCHN without HIV. LEVEL OF EVIDENCE: 2b.

OBJECTIVES/HYPOTHESIS: To report the long-term outcomes of radiation therapy (RT), and the impact of fractionation size and RT duration on HIV patients with Benign Lymphoepithelial Cysts (BLEC) of the parotid glands. METHODS: From January 2000 to 2011, 30 patients were eligible for our single institution retrospective study. Both parotids were treated with 24 Gy via RT. The median age at RT, HIV diagnosis, and duration of HIV seropositive was 45 years (28-64), 38 years (23-53), and 11 years (6-35), respectively. Patients were stratified into two groups. Group A and B received 2Gyx12 and 1.5Gyx16, respectively. RESULTS: After a median follow-up of 66 months (12-141), the overall response (OvR) was 93% of the patients. Specifically, complete response (CR) and partial response (PR) were 80% and 13%, respectively. In group A, 100% had CR. Treatment failure was 7% and all were in group B, which was mainly due to poor compliance. A Chi-square test showed significant relationship between OvR and RT duration (P <0.001), and a positive trend between CR and fraction size of 2 Gy (P = 0.053). All acute toxicities were grade