Novel molecular imaging techniques have the potential to significantly enhance the diagnostic and therapeutic approaches for cancer treatment. For solid tumors in particular, novel molecular enhancers for imaging modalities such as US, CT, MRI and PET may facilitate earlier and more accurate diagnosis and staging which are prerequisites for successful surgical therapy. Enzymatically activatable “smart” molecular MRI probes seem particularly promising because of their potential to image tumors before and after surgical removal without re-administration of the probe to evaluate completeness of surgical resection. Furthermore, the use of “smart” MR probes as part of screening programs may enable detection of small tumors throughout the body in at-risk patient populations. Dual labeling of molecular MR probes with fluorescent dyes can add real time intraoperative guidance facilitating complete tumor resection and preservation of important structures. A truly theranostic approach with the further addition of therapeutic agents to the molecular probe for adjuvant therapy is conceivable for the future.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of pathologically expanded myeloid cells with immunosuppressive activity. In human disease, three major MDSC subpopulations can be defined as monocytic (M-MDSC), granulocytic [polymorphonuclear-MDSC (PMN-MDSC)], and early stage (e-MDSC), which lacks myeloid lineage markers of the former two subsets. The purpose of this study was to determine and compare the immunosuppressive capacity and clinical relevance of each of these subsets in patients with solid cancer. The frequency of MDSC subsets in the peripheral blood was determined by flow cytometry in a cohort of 49 patients with advanced head and neck cancer (HNC) and 22 patients with urological cancers. Sorted and purified MDSC subsets were tested for their T-cell-suppressive capacity. Frequency of circulating MDSC was correlated with overall survival of patients with HNC. A high frequency of PMN-MDSC most strongly correlated with poor overall survival in HNC. T-cell-suppressive activity was higher in PMN-MDSC compared with M-MDSC and e-MDSC. A subset of CD66b/CD11b/CD16 mature PMN-MDSC displayed high expression and activity of arginase I, and was superior to the other subsets in suppressing proliferation and cytokine production of T cells in both cancer types. High levels of this CD11b/CD16 PMN-MDSC, but not other PMN-MDSC subsets, strongly correlated with adverse outcome in HNC. A subset of mature CD11b/CD16 PMN-MDSC was identified as the MDSC subset with the strongest immunosuppressive activity and the highest clinical relevance. .

Background: Age at diagnosis is incorporated into all relevant staging systems for differentiated thyroid carcinoma (DTC). There is growing evidence that a specific age cutoff may not be ideal for accurate risk stratification. We sought to evaluate the interplay between age and oncologic variables in patients with DTC using the largest cohort to date. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with DTC as their only malignancy for the period 1973 to 2009. Multivariate analyses using a range of age cutoffs and age subgroupings were utilized in order to search for an optimal age that would provide the most significant risk stratification between young and old patients. The primary outcome was disease-specific survival (DSS) and covariates included: age, race, sex, tumor/nodal/metastasis (TNM) stage, decade of diagnosis, and radioactive iodine therapy. Results: A total of 85,740 patients were identified. Seventy-six percent of patients were American Joint Committee on Cancer (AJCC) stage I, 8% were stage II, 7% were stage III, and 8% were stage IV. Age over 45 years (hazard ratio [HR] 19.2, p < 0.001) and metastatic disease (HR 13

Radioactive iodine (RAI) is a key component in the treatment of differentiated thyroid cancer. RAI has been recommended more selectively in recent years as guidelines evolve to reflect risks and utility in certain patient subsets. In this study we sought to evaluate the survival impact of radioactive iodine in specific thyroid cancer subgroups. Nationwide retrospective cohort study of patients using the National Cancer Database (NCDB) from 2004-2012 and Surveillance, Epidemiology, and End Results (SEER) database from 1992-2009 examining patients with differentiated thyroid cancer treated with or without RAI. Primary outcomes included all-cause mortality (NCDB and SEER), and cancer-specific mortality (SEER). Cox multivariate survival analyses were applied to each dataset, and in 135 patient subgroups based on clinical and non-clinical parameters. A total of 199,371 NCDB and 77,187 SEER patients were identified. RAI was associated with improved all-cause mortality (NCDB: RAI hazard ratio (HR) 0.55, P<0.001; SEER: HR 0.64, P<0.001); and cancer-specific mortality (SEER: HR 0.82, P=0.029). Iodine therapy showed varied efficacy within each subgroup. Patients with high-risk disease experienced the greatest benefit in all-cause mortality, followed by intermediate-risk, then low-risk subgroups. Regarding cancer-specific mortality, radioactive iodine therapy was protective in high-risk patients, but did not achieve statistical significance in most intermediate-risk subgroups. Low-risk T1a subgroups demonstrated an increased likelihood of cancer-specific mortality with iodine therapy. The efficacy of RAI in patients with differentiated thyroid cancer varies by disease severity. A negative cancer-specific survival association was identified in patients with T1a disease. These findings warrant further evaluation with prospective studies.

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Nerve degeneration after transection injury decreases intraoperative visibility under white light (WL), complicating surgical repair. We show here that the use of fluorescently labeled nerve binding probe (F-NP41) can improve intraoperative visualization of chronically (up to 9 months) denervated nerves. In a mouse model for the repair of chronically denervated facial nerves, the intraoperative use of fluorescent labeling decreased time to nerve identification by 40% compared to surgeries performed under WL alone. Cumulative functional post-operative recovery was also significantly improved in the fluorescence guided group as determined by quantitatively tracking of the recovery of whisker movement at time intervals for 6 weeks post-repair. To our knowledge, this is the first description of an injectable probe that increases visibility of chronically denervated nerves during surgical repair in live animals. Future translation of this probe may improve functional outcome for patients with chronic denervation undergoing surgical repair.

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Neutrophil extracellular traps (NETs) represent web-like structures consisting of externalized DNA decorated with granule proteins that are responsible for trapping and killing bacteria. However, undesirable effects of NET formation during carcinogenesis, such as metastasis support, have been described. In the present study, we evaluated the correlation between NETosis and disease progression in head and neck cancer (HNC) patients in order to establish a valid biomarker for an early detection and monitoring of HNC progression. Moreover, factors influencing NET release in HNC patients were revealed. We showed a significantly elevated vital NETosis in neutrophils isolated from early T1–T2 and N0–N2 stage patients, as compared to healthy controls. Additionally, in our experimental setting, we confirmed the involvement of tumor cells in the stimulation of NET formation. Interestingly, in advanced cancer stages (T3–4, N3) NETosis was reduced. This also correlated with the levels of granulocyte colony-stimulating factor (G-CSF) in plasma and tumor tissue. Altogether, we suggest that the elevated NETosis in blood can be used as a biomarker to detect early HNC and to predict patients at risk to develop tumor metastasis. Therapeutic disruption of NET formation may offer new roads for successful treatment of HNC patients in order to prevent metastasis.