Background Surgical resection remains the most effective therapy for solid tumors worldwide. The most important prognostic indicator for cure following cancer surgery is a complete resection with no residual disease. However, intraoperative detection of retained cancer cells after surgery is challenging, and residual disease continues to be the most common cause of local failure. We hypothesized visual enhancement of tumors using near-infrared imaging could potentially identify tumor deposits in the wound after resection. Methods A small animal model of surgery and retained disease was developed. Residual tumor deposits in the wound were targeted using an FDA approved imaging agent, indocyanine green, by the enhanced permeability and retention (EPR) effect. A novel hand-held spectrometer was used to optically visualize retained disease after surgery. Results We found residual disease using near-infrared imaging during surgery that was not visible to the naked eye or microCT. Furthermore, examination of tumor nodules was remarkably precise in delineating margins from normal surrounding tissues. This approach was most successful for tumors with increased neovasculature. Conclusions The results suggest that near-infrared examination of the surgical wound after curative resection can potentially enable the surgeon to locate residual disease. The data in this study is the basis of an ongoing Phase I/II clinical trial in patients who undergo resection for lung and breast cancer.

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Background:In this study, we evaluate whether the use of biliverdin (BV), a natural non-toxic antioxidant product of haeme catabolism, can suppress head and neck squamous cell carcinoma (HNSCC) cell proliferation and improve the tumour survival both in vitro and in vivo. Furthermore, we investigate whether this therapeutic outcome relies on BV's potent antioxidant effect on reactive oxygen species (ROS)-mediated signalling.Methods:Two well-characterised HNSCC cell lines and a mouse model with human HNSCC were used for this study. In vitro, the effect of BV on ROS was assayed. Subsequently, critical regulatory proteins involved in growth, antiapoptotic, and angiogenic pathways were investigated by western blot analysis. In addition, the antiproliferative effect of BV was also evaluated using the clonogenic assay. Moreover, tumour growth inhibition was assessed using a mouse model with HNSCC.Results:Biliverdin treatment resulted in decreased ROS, leading to suppression of proliferation and angiogenesis pathways of HNSCC, significantly decreasing the expression and phosphorylation of oncogenic factors such as epidermal growth factor receptor (EGFR), phosphorylation of Akt, and expression of angiogenic marker and transcription factor, hypoxia-inducible factor1-α (HIF1-α). Furthermore, this downregulation of ROS by BV led to a significant suppression of tumour growth in vivo.Conclusions:Our study demonstrates the efficacy of a novel therapeutic approach using BV as an antitumour agent against HNSCC through its effect on EGFR/Akt and HIF1-α/angiogenesis signal transduction pathways. Our findings indicate that BV's inhibitory effect on these tumorigenic pathways relies on its antioxidant effect, and may extend its therapeutic potential to other solid cancers.

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The results of this study suggest that if a PEG placement is indicated for a TBI patient, a standard (7 to 14 d) timing may be associated with better patient outcomes. However, secondary to limitations associated with the use of administrative databases, further prospective studies are needed to establish clear guidelines regarding the optimal timing of placing PEG in TBI patients.

Primary colorectal squamous cell carcinoma (SCC) is one of the very rare malignancies of the gastrointestinal tract. The diagnosis cannot be made before ruling out other common primary sites. Using the endoscopic ultrasound (EUS) technique to get a tissue biopsy for submucosal tumors has not been demonstrated as the best diagnostic approach in the literature. Surgery is the gold standard treatment with arising evidence of good efficacy following conventional chemoradiation therapy. A 49-year-old male presented with rectal discomfort. Sigmoidoscopy revealed multiple submucosal masses in the rectosigmoid colon. Mucosal biopsies showed nonspecific inflammation. Subsequently, an EUS with fine needle biopsy was done and established the diagnosis of rectal SCC. There were no other primary sites noticed in the extensive evaluation. The patient chose to be treated only with chemoradiation without surgery. At the time of writing this report he had no evidence of recurrence achieving 2.5 years of survival. EUS is an emerging excellent approach to diagnose submucosal colorectal SCC. This case will add supportive evidence of having a complete response following combining treatment with squamous cell directed chemotherapy and external beam radiotherapy without preceded surgery.

Objectives: 1) Develop an accurate detection system for head and neck squamous cell carcinoma (HNSCC) using tumor specific nanoparticle-based probes. 2) Apply these probes for real-time non-invasive HNSCC detection using molecular imaging (MI) system. Methods. Fluorescence-labeled LDS nanoparticles targeting Hsp47 (a highly specific biomarker for HNSCC) were constructed. The HNSCC targeted properties of these constructs were evaluated in vitro using human HNSCC tumor cell lines and in a mouse model of HNSCC with a MI system. Results: Fluorescence-labeled LDS nanoparticles demonstrated HNSCC tumor cell targeting properties in vitro. Furthermore, this targeting strategy demonstrated accurate and real time tumor detection using MI system. Conclusions: Our study suggests that these novel nanoparticle-based HNSCC tumor-targeting constructs have the potential to be used clinically for non-invasive, accurate, and real time detection of tumors for patients evaluated for HNSCC.

Objectives: 1) Develop a novel chitosan-hydrogel-based nanoparticle delivery system (nanohydrogel) for inner ear application and to evaluate its structures and release kinetics in vitro. 2) Evaluate if the nanohydrogel delivery system can be turned off using an enzymatic regulator for inner ear delivery. 3) Evaluate the inner ear distribution of nanoparticles following round window membrane application in a mouse model. Methods: Nanoparticles labeled with fluorescence were constructed and loaded into a chitosan-based hydrogel to form a nanohydrogel delivery system. In vitro studies were performed to evaluate the thermosensitivity, structure, and nanoparticle release kinetics of the nanohydrogel with/without chitosanase enzymatic regulation. Morphologic studies were performed to evaluate the nanoparticle delivery and distribution within the inner ear structures in a mouse model. Results: After obtaining a homogeneous, viscous and thermosensitive nanohydrogel system, in vitro studies showed that the nanohydrogel can carry and release nanoparticles in a controlled and sustained manner, and chitosanase can effectively regulate this release if needed. A matrix-like ultrastructure containing nanosized particles was confirmed. In vivo findings further confirm that the nanohydrogel delivered nanoparticles into the perilymphatic system and reached cellular structures of the inner ear in our mouse model. Conclusions: Our study suggests that the nanohydrogel system has the potential to safely deliver drugs or biomaterials in a controlled and sustained manner for inner ear application. This system could be used for targeted therapy for inner ear diseases that require safe and non-invasive delivery approaches.