Invadopodia are branched actin-rich structures associated with extracellular matrix (ECM) degradation that collectively form the invasive machinery of aggressive cancer cells. Cortactin is a prominent component and a specific marker of invadopodia. Amplification of cortactin is associated with poor prognosis in head and neck squamous cell carcinomas (HNSCC), possibly because of its activity in invadopodia. Although the role of cortactin in invadopodia has been attributed to signaling and actin assembly, it is incompletely understood. We made HNSCC cells deficient in cortactin by RNA interference knockdown methods. In these cortactin knockdown cells, invadopodia were reduced in number and lost their ability to degrade ECM. In the reverse experiment, overexpression of cortactin dramatically increased ECM degradation, far above and beyond the effect on formation of actin/Arp3-positive invadopodia puncta. Secretion of matrix metalloproteinases (MMP) MMP-2 and MMP-9, as well as plasma membrane delivery of MT1-MMP correlated closely with cortactin expression levels. MMP inhibitor treatment of control cells mimicked the cortactin knockdown phenotype, with abolished ECM degradation and fewer invadopodia, suggesting a positive feedback loop in which degradation products from MMP activity promote new invadopodia formation. Collectively, these data suggest that a major role of cortactin in invadopodia is to regulate the secretion of MMPs and point to a novel mechanism coupling dynamic actin assembly to the secretory machinery, producing enhanced ECM degradation and invasiveness. Furthermore, these data provide a possible explanation for the observed association between cortactin overexpression and enhanced invasiveness and poor prognosis in HNSCC patients. [Cancer Res 2007;67(9):4227-35]

11q13 amplification is a late-stage event in several cancers that is often associated with poor prognosis. Among 11q13-amplified genes, the actin assembly protein cortactin/CTTN is considered a likely candidate for direct involvement in tumor progression, because of its cell motility-enhancing functions. We modulated cortactin expression in head and neck squamous cell carcinoma (HNSCC) lines. Cortactin expression levels directly correlated with tumor size, vascularization, and cell proliferation in an orthotopic HNSCC in vivo model. In contrast, under normal in vitro culture conditions, cortactin expression levels had no effect on cell proliferation. However, cell lines in which cortactin expression was reduced by knockdown (KD) grew poorly in vitro under harsh conditions of growth-factor deprivation, anchorage independence, and space constraint. Conversely, overexpression of cortactin enhanced in vitro growth under the same harsh conditions. Surprisingly, defects in growth factor-independent proliferation of cortactin-KD cells were rescued by co-culture with cortactin-expressing cells. Since the co-cultured cells are separated by permeable filters, cortactin-expressing cells must secrete growth-supporting autocrine factors to rescue the cortactin-KD cells. Overall, cortactin expression modulates multiple cellular traits that may allow survival in a tumor environment, suggesting that the frequent overexpression of cortactin in tumors is not an epiphenomenon but rather promotes tumor aggressiveness.

A period lasting an average of 187 msec was seen during mid-diastole (72+/-5% of the cardiac cycle) in which all three coronary arteries studied had relatively little motion. This period of quiescence was consistent along the length of the arteries. Although the amount of motion did vary along the length of the arteries, there was no difference in the timing of rest periods in the proximal, mid, and distal segments using a < 1 mm per frame threshold. The periods of low motion were significantly reduced in length and often altogether eliminated when the 0.5 mm per frame threshold was used.

Balloon dilation plays an important role in the primary and adjuvant management of pediatric SGS. The presence of concomitant airway lesions is significantly associated with failure of balloon dilation treatment. Meticulous surveillance of the dilated airway is necessary, given this failure rate.

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Background: Since the start of the COVID-19 pandemic outpatient medicine has drastically been altered how it is delivered. This time period likely represents the largest volume of telehealth visits in the United States health care history. Telehealth presents unique challenges within each subspecialty, and pediatric otolaryngology is no different. This retrospective review was designed to evaluate our division of pediatric otolaryngology’s experience with telehealth during the COVID19 pandemic. Methods: This study was approved by the Institutional Review Board at Vanderbilt University Medical Center. All telehealth and face-to-face visits for the month of April 2020 completed by the Pediatric Otolaryngology Division were reviewed. A survey, utilizing both open-ended questions and Likert scaled questions was distributed to the 16 pediatric otolaryngology providers in our group to reflect their experience with telehealth during the 1-month study period. Results: In April, 2020 our outpatient clinic performed a total of 877 clinic visits compared to 2260 clinic visits in April 2019. A total of 769 (88%) were telehealth visits. Telemedicine with video comprised 523 (68%) and telephone only comprised 246 (32%). There were 0 telehealth visits in April 2019. Interpretive services were required in 9.3% (N = 211) clinic visits in April 2019 and 7.5% (N = 66) of clinic visits in April 2020. The survey demonstrated a significant difference ( P < .00002) in provider’s anticipated telehealth experience (mean 3.94, 95% CI [3.0632, 4.8118] compared to their actual experience after the study period (mean 7.5, 95% CI [7.113, 7.887]. Conclusions: Despite low initial expectations for telehealth, the majority of our providers felt after 1 month of use that telehealth would continue to be a valuable platform post-pandemic clinical practice. Limited physical exam, particularly otoscopy, nasal endoscopy, and nasolaryngoscopy present challenges. However, with adequate information and preparation for the parents and for the physician some of the obstacles can be overcome.

Health status instruments are questionnaires that are utilized to assess changes in health status of individuals. These surveys are increasingly of importance as health care providers are challenged to justify treatment approach and rationale. Objective criteria (e.g. CT scan of the sinuses) can be used to determine whether there is clinical evidence of disease. However, the impact of the disease on the individual’s life is not included in such a clinical assessment. The use of validated and reliable health instruments is directed at measuring this impact in a reproducible and valid fashion. In patient-centered research, ‘experimental’ conditions are constantly changing because we are dealing with human beings with values, feelings, and perspectives. It is especially important to use valid measurement tools when assessing these impacts. This article outlines the principles of the development and validation of health status instruments and offers examples of such instruments from the otolaryngology literature.

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