Research Spotlight

Wayson, M. B. and W. E. Bolch (2018). “Individualized adjustments to reference phantom internal organ dosimetry-scaling factors given knowledge of patient external anatomy.” Phys Med Biol 63(8): 085007.

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Internal radiation dose estimates for diagnostic nuclear medicine procedures are typically calculated for a reference individual. Resultantly, there is uncertainty when determining the organ doses to patients who are not at 50th percentile on either height or weight. This study aims to better personalize internal radiation dose estimates for individual patients by modifying the dose estimates calculated for reference individuals based on easily obtainable morphometric characteristics of the patient. Phantoms of different sitting heights and waist circumferences were constructed based on computational reference phantoms for the newborn, 10 year-old, and adult. Monoenergetic photons and electrons were then simulated separately at 15 energies. Photon and electron specific absorbed fractions (SAFs) were computed for the newly constructed non-reference phantoms and compared to SAFs previously generated for the age-matched reference phantoms. Differences in SAFs were correlated to changes in sitting height and waist circumference to develop scaling factors that could be applied to reference SAFs as morphometry corrections. A further set of arbitrary non-reference phantoms were then constructed and used in validation studies for the SAF scaling factors. Both photon and electron dose scaling methods were found to increase average accuracy when sitting height was used as the scaling parameter (~11%). Photon waist circumference-based scaling factors showed modest increases in average accuracy (~7%) for underweight individuals, but not for overweight individuals. Electron waist circumference-based scaling factors did not show increases in average accuracy. When sitting height and waist circumference scaling factors were combined, modest average gains in accuracy were observed for photons (~6%), but not for electrons. Both photon and electron absorbed doses are more reliably scaled using scaling factors computed in this study. They can be effectively scaled using sitting height alone as patient-specific morphometric parameter.

Su, T., J. Liao, Z. Dai, L. Xu, S. Chen, Y. Wang, Z. Peng, Q. Zhang, S. Peng and M. Kuang (2018). “Stress-induced phosphoprotein 1 mediates hepatocellular carcinoma metastasis after insufficient radiofrequency ablation.” Oncogene 37(26): 3514-3527.

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Recent studies indicated that insufficient radiofrequency ablation (RFA) could endow hepatocellular carcinoma (HCC) with higher aggressive potential. Stress-induced phosphoprotein 1 (STIP1), which was found highly expressed in HCC, is a chaperone molecule mediating cell homeostasis under thermal stress. We aimed to explore the role of STIP1 on the metastasis of residual HCC after RFA. Mice model with orthotopic HCC implants or caudal vein injection were employed to assess potential of lung metastasis and/or intrahepatic metastasis (IHM) of HCC cells. Cell culture model was used to determine cell invasion, mesenchymal marker genes expression, and underlying molecular mechanisms. Clinical specimens were collected to analyze the relationship between STIP1 and clinical outcome. We found that insufficient RFA elicited more IHM of HCCLM3 tumors, which could be reduced by silencing STIP1. Knockdown of STIP1 also significantly decreased lung metastatic potential of HCCLM3 cells. In vitro, HCCLM3 and HepG2 displayed a spindle-shaped morphology with upregulation of STIP1 and mesenchymal markers after sublethal heat exposure. Mechanistically, heat exposure induced the formation of STIP1-heat shock protein 90 (HSP90) complex, which could shuttle epithelial transcription repressor Snail1 into nucleus and regulate mesenchymal gene transcription. Blocking the HSP90-STIP1 complex reduced the invasive potential of HCC cells after heat exposure. Using clinical specimen, we found that STIP1 was expressed significantly higher in metastatic tumor tissues and in sera from metastatic HCC patients (p < 0.05). The high expression of STIP1 was significantly linked to shorter recurrence-free survival (p < 0.05). To sum up, our study found that STIP1 is positively associated with the sublethal heat-induced cancer cell metastasis through mediating the mesenchymal gene transcription. Blocking STIP1 activity may suppress HCC cell metastatic potential after RFA.

Zhai, E., W. Liang, Y. Lin, L. Huang, X. He, S. Cai, J. Chen, N. Zhang, J. Li, Q. Zhang, Y. He, Z. Zeng, M. Chen, L. Xu and S. Peng (2018). “HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer.” Cell Physiol Biochem 47(2): 879-892.

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BACKGROUND/AIMS: HSP70/HSP90-organizing protein (HOP) is an adaptor protein that mediates heat shock protein 70 (HSP70) and HSP90 folding. HOP can be secreted by cancer cells and promote malignant cell growth in an autocrine manner. Here, we studied its role in gastric cancer (GC). METHODS: HOP mRNA and protein levels were detected by quantitative real-time PCR and western blotting, respectively, and enzyme-linked immunosorbent assay was used to determine the serum levels. Immunohistochemistry was performed to analyze HOP expression in 117 GC tissues and 32 adjacent normal tissues. The Cell Counting Kit-8 cell viability assay, flow cytometry, and western blotting were used to analyze the effects of HOP on cell proliferation and apoptosis, and the potential underlying mechanisms. RESULTS: HOP mRNA and protein levels were significantly higher in GC tissues than in normal tissues in our medical center (P< 0.001) and in The Cancer Genome Atlas database (P< 0.001). GC patients had higher serum levels of HOP than age-matched healthy controls (P< 0.001); however, once tumors were removed, serum levels significantly decreased (P< 0.01). In human GC tissues, increased HOP expression was associated with tumor progression and poor survival. Notably, autocrine HOP promoted cell proliferation through the phospholipase Cgamma1-extracellular signal-regulated kinase 1/2-dependent pathway, and inhibited cell apoptosis by regulating the activities of caspase 9, caspase 3, and B-cell lymphoma 2. Blocking extracellular HOP with neutralizing antibody reduced proliferation and enhanced fluorouracil-induced apoptosis of GC cells. CONCLUSIONS: Our findings demonstrate that HOP is an important molecular marker and prognostic factor for GC, and functionally contributes to tumor cell growth and survival. These results provide a rationale for considering HOP as a potential therapeutic target and chemosensitizer in GC.

Zerillo, J., M. Ramsay, M. S. Mandell and T. Sakai (2018). “An Update in Abdominal Organ Transplantation Anesthesia in 2018: Society for the Advancement of Transplant Anesthesia (SATA).” Semin Cardiothorac Vasc Anesth 22(2): 109-110.

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This special edition of Seminars in Cardiothoracic and Vascular Anesthesia is the product of a new collaborative venture with the Society for the Advancement of Transplant Anesthesia (SATA). SATA is an international organization that is a societal home for anesthesiologists and critical care physicians who specialize in the field of organ transplantation. We asked experts among the SATA membership to provide scholarly updates in problematic areas of clinical practice for abdominal organ transplant anesthesiologists. There was special focus on patients undergoing liver transplantation as this is a rapidly evolving area of practice. This edition provides a mix of clinically relevant original research as well as reviews with thought-provoking commentary about the allocation of scarce organs. (Excerpt from text of this commentary, p. 109; no abstract available.)

Yuen, H., P. E. Rossouw, L. M. Wolford and H. Wang (2018). “Pharyngeal Airway Space Changes After Condylar Replacement and Mandibular Advancement Surgery.” J Oral Maxillofac Surg 76(6): 1165-1174.

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PURPOSE: The aim of this study was to examine the total volume and cross-sectional areas of the pharyngeal airway after bilateral condylar replacement and mandibular advancement surgery. MATERIALS AND METHODS: A total of 137 patients (126 women and 11 men) underwent bilateral temporomandibular joint total joint replacement performed by 1 surgeon. A subsample of 30 patients who underwent condylar replacement and only mandibular advancement were evaluated for impact on the airway. Measurements were taken preoperatively, postoperatively, and at a follow-up 1 year after surgery on cone beam computed tomography scans. InVivoDental 3-dimensional imaging (Anatomage, San Jose, CA) was used to measure airway space regarding total volume (in cubic centimeters); minimum cross-sectional area (in square millimeters); minimum cross sections of the first, second, and third cervical vertebrae; and whether the patient had mandibular retrognathia before surgery. A second operator was used to test for interoperator error. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: There was a significant increase in all measurements at the follow-up visit compared with the preoperative visit. There were no significant differences between groups based on simultaneous Le Fort I surgery, mandibular retrognathia, and gender. However, there were statistically significant differences in cross sections 1 and 2, as well as minimum cross-sectional area, regarding age. Condylar replacement and mandibular advancement have a significant association with an increase in airway space. The intraclass correlation coefficient showed excellent agreement between interoperator measurements. CONCLUSIONS: Patients undergoing bilateral temporomandibular joint replacement and mandibular advancement surgery showed an increase in pharyngeal airway space at a 1-year follow-up. In this study, age was significantly associated with the cross-sectional areas of the airway, with older patients having smaller values.