Background Reflectance confocal microscopy (RCM) is a noninvasive tool that is used to diagnose skin cancers. However, RCM requires an expert consultation, which is often performed via store-and-forward (SAF) teledermatology. Unfortunately, SAF does not mimic bedside diagnosis, nor permits interaction between the remote expert reader, physician, and patient. Recently, a live interactive method (LIM)–tele-RCM approach was shown to diagnose basal cell carcinoma (BCC) from a remote location, demonstrating advantages over SAF by providing a bedside diagnosis during consultation. Objective The aim of this study is to validate the LIM-tele-RCM approach to diagnose BCC in a real-world setting. Methods In this pilot study, 4 patients with 6 clinically suspicious BCC lesions were enrolled and imaged with RCM at a Los Angeles dermatology clinic. A Health Insurance Portability and Accountability Act–compliant teleconferencing application was used to livestream RCM images to an expert RCM reader in New York. The expert reader had remote control of the software, direct audio communication with the clinic, and the patient’s clinical history with dermoscopy. During imaging, RCM features were noted, and a diagnosis was made at the bedside. After imaging, patients completed a short questionnaire (on a 5-point scale, with 5 being the highest score) about satisfaction, comfort, and communication during the session. Results RCM diagnosed 4/6 (67%) lesions correctly as BCC and 2/6 (33%) were false-positive diagnoses. The true-positive lesions had “tumor islands with palisading and clefting” and were directly managed with Mohs surgery. The false-positive lesions had “dark silhouettes” (a common false-positive feature for BCC) and underwent a shave biopsy for confirmation. The entire session ranged from 15 to 20 minutes (an average of 17.7 minutes), comparable to the reported RCM procedure time. On the questionnaire, all patients responded with the highest rating (5/5) for each question. Conclusions LIM-tele-RCM demonstrates potential advantages over the SAF method, enabling bedside diagnosis with similar diagnostic accuracy as reported in the literature and proper management. Additionally, the remote reader had access to patients’ clinical backgrounds and could engage with patients. It may also be useful for training novice RCM users and beneficial in settings where remote diagnostics are desired, such as during the COVID-19 pandemic. However, technical challenges such as image quality degradation during video streaming, poor internet bandwidth, and end user latency may impact diagnosis. Larger, multicenter studies are needed to assess the accuracy of LIM-tele-RCM for the diagnosis of BCC and other neoplastic and inflammatory lesions, and to quantify technical limitations. Acknowledgments This work was funded by the National Cancer Institute Cancer Center (Grant P30 CA008748). Conflicts of Interest None declared.
BACKGROUND Reflectance confocal microscopy (RCM) is a noninvasive tool that is used to diagnose skin cancers. However, RCM requires an expert consultation, which is often performed via store-and-forward (SAF) teledermatology. Unfortunately, SAF does not mimic bedside diagnosis, nor permits interaction between the remote expert reader, physician, and patient. Recently, a live interactive method (LIM)–tele-RCM approach was shown to diagnose basal cell carcinoma (BCC) from a remote location, demonstrating advantages over SAF by providing a bedside diagnosis during consultation. OBJECTIVE The aim of this study is to validate the LIM-tele-RCM approach to diagnose BCC in a real-world setting. METHODS In this pilot study, 4 patients with 6 clinically suspicious BCC lesions were enrolled and imaged with RCM at a Los Angeles dermatology clinic. A Health Insurance Portability and Accountability Act–compliant teleconferencing application was used to livestream RCM images to an expert RCM reader in New York. The expert reader had remote control of the software, direct audio communication with the clinic, and the patient’s clinical history with dermoscopy. During imaging, RCM features were noted, and a diagnosis was made at the bedside. After imaging, patients completed a short questionnaire (on a 5-point scale, with 5 being the highest score) about satisfaction, comfort, and communication during the session. RESULTS RCM diagnosed 4/6 (67%) lesions correctly as BCC and 2/6 (33%) were false-positive diagnoses. The true-positive lesions had “tumor islands with palisading and clefting” and were directly managed with Mohs surgery. The false-positive lesions had “dark silhouettes” (a common false-positive feature for BCC) and underwent a shave biopsy for confirmation. The entire session ranged from 15 to 20 minutes (an average of 17.7 minutes), comparable to the reported RCM procedure time. On the questionnaire, all patients responded with the highest rating (5/5) for each question. CONCLUSIONS LIM-tele-RCM demonstrates potential advantages over the SAF method, enabling bedside diagnosis with similar diagnostic accuracy as reported in the literature and proper management. Additionally, the remote reader had access to patients’ clinical backgrounds and could engage with patients. It may also be useful for training novice RCM users and beneficial in settings where remote diagnostics are desired, such as during the COVID-19 pandemic. However, technical challenges such as image quality degradation during video streaming, poor internet bandwidth, and end user latency may impact diagnosis. Larger, multicenter studies are needed to assess the accuracy of LIM-tele-RCM for the diagnosis of BCC and other neoplastic and inflammatory lesions, and to quantify technical limitations.
The purpose of this study is to provide further evidence that Thymidine Kinase I (TK1) is selectively expressed on the surface of lung cancer cells, and therefore could be utilized as a potential molecular target. TK1 is an enzyme in the pyrimidine salvage pathway whose expression is closely correlated with cell proliferation and cell turnover. It has previously been shown that upregulation of TK1 is an early event in the development of most cancers. Additionally TK1 serum levels in cancer patients correlate with tumor progression and cancer aggressiveness. Moreover TK1 levels in the original tumors have also been shown to correlate directly with tumor recurrence thus making TK1 a useful prognostic marker in clinical oncology. Recent studies in our lab have provided evidence that TK1 is localized on the plasma membrane in lung cancer cells. Using scanning electron microscopy (SEM), flow cytometry, confocal microscopy and tissue staining, we confirmed the presence of TK1 on the cell surface of H460 cells. Using normal lymphocytes as a comparative control we found TK1 expression on lung cancer cells to be significantly increased compared to control cells. For this investigation, we used three custom designed monoclonal antibodies against human TK1 conjugated with FITC, namely CB1, A72 and A74. Using flow cytometry we confirmed the presence of TK1 on the cell surface, our data shows that H460 cells stained positive for TK1 (12% for A72, 19% for A74, and 29% for CB1). Furthermore, confocal microscopy indicated a positive fluorescent signal for A72, A74 and CB1, suggesting the presence of TK1 on the plasma membrane. SEM images of lung cancer cells and normal lymphocytes stained with TK1 antibodies and gold labeling reported a positive gold signal on H460 cells with relatively no signal from human lymphocytes. Immunohistochemistry staining of carcinoma tissue array panels compared with normal tissue array panels indicated a statistical significant difference of expression levels of TK1 between normal lung tissue and lung carcinoma (P value <0.05). Positive staining was considered if more than 5% of the cells were stained. There was negligible staining in normal lung tissue. Using these techniques we confirmed that TK1 is selectively expressed on the surface of H460 cells and not on normal cells. These results suggest that TK1 could be used as a possible molecular target in lung cancer therapy. Further studies are currently ongoing to monitor TK1 expression and progression to help to elucidate the mechanisms behind it's over expression in cancer cells and to track its progression and movement from the cytosol to the cell surface. Citation Format: Edwin J. Velazquez, Evita G. Weagel, Wei Meng, Michelle H. Townsend, Alex Cummonck, Craig Chandler, Michael R. Downey, Richard Robison, Kim L. O’Neill. A novel molecular target for lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1273.
The aim of this study is to determine whether Thymidine Kinase 1 (TK1) would be a suitable target for future immunotherapeutic treatment of colon cancer. The salvage pathway enzyme TK1 has been shown to be upregulated in cancer patients due to active proliferation of cancer cells and the resulting high demand for nucleotides. Present in both the cytosol and the serum of cancer patients, TK1 levels can be used to not only predict cancer occurrence, but also to predict tumor aggressiveness and future remission. While serum levels of TK1 have been established, surface expression of the enzyme have not been fully characterized. In colon cancer cells, TK1 has been shown to strongly associate with the plasma membrane. In this project we explored the presence of TK1 on the surface of colon cancer cells (HT29 and SW620 cell lines) using flow cytometry, confocal microscopy, scanning electron microscopy, membrane separation, and cytoplasmic staining. Using fluorescent antibodies conjugated to FITC, expression levels as high as 19% are observed in HT29's and 12% in SW620's in comparison to sodium potassium ATPase surface levels of 11% and 6% respectively. Confocal microscopy images revealed direct overlap between cells stained with a rhodamine red membrane dye and with a FITC conjugated anti-TK1 antibody which indicates a direct relationship between TK1 and the cellular surface of cancer cells. To further confirm surface expression, TK1 levels were assessed using gold labeling and scanning electron microscopy. Gold levels indicate the physical location of the TK1 on the surface of the colon cancer cells and their relative abundance. TK1 surface levels in colon cancer cells corresponded with the surface expression levels of sodium potassium ATPase and share relatively the same abundance. These results strongly indicate a direct relationship between TK1 and the surface of colon cancer cells, and suggests TK1 as a potential target for future immunotherapeutic treatment. Citation Format: Michelle H. Townsend, Evita G. Weagel, Wei Meng, Craig Chandler, Richard A. Robison, Kim L. O’Neill. Cancer immunotherapy: Could TK1 be used as a target for colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3863.
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