// Shailendra Kumar Dhar Dwivedi 1 , Scott D. McMeekin 1 , Katrina Slaughter 1 and Resham Bhattacharya 1 1 Department of Obstetrics and Gynecology, Stephenson Cancer Center, University of Oklahoma Health Science Center, Oklahoma, USA Correspondence to: Resham Bhattacharya, email: // Keywords : uterine carcinosarcoma, EMT, c-Myc, TGF beta Received : January 20, 2015 Accepted : March 03, 2015 Published : March 30, 2015 Abstract Uterine carcinosarcomas (UCS) are rare (3-4%) but highly aggressive, accounting for a disproportionately high (16.4%) mortality among uterine malignancies. Transforming growth factor beta (TGFβ) is a multifunctional cytokine that regulates important cellular processes including epithelial-mesenchymal transition (EMT). Existence of biphasic elements and a report demonstrating amplification of TGFβ at 19q13.1 prompted us to investigate the role of TGFβ signaling in UCS. Here we demonstrated the components of TGFβ pathway are expressed and functional in UCS. TGFβ-I induced significant Smad2/3 phosphorylation, migration and EMT responses in UCS cell lines which could be attenuated by the TGFβ receptor I (TGFβR-I) or TGFβ receptor I/II (TGFβR-I/II) inhibitor developed by Eli Lilly and company. Importantly, TGFβ-I induced proliferation was c-Myc dependent, likely through activation of cell cycle. c-Myc was induced by nuclear translocation of nuclear factor of activated T cells (NFAT-1) in response to TGFβ-I. Inhibition of NFAT-1 or TGFβR-I blocked c-Myc induction, cell cycle progression and proliferation in UCS. In corroboration, mRNA levels of c-Myc were elevated in recurrent versus the non-recurrent UCS patient samples. Interestingly, in the absence of exogenous TGFβ the TGFβR-I/II inhibitor enhanced proliferation likely through non-Smad pathways. Thus, inhibition of TGFβR-I could be efficacious in treatment of UCS.
Proper tongue function is essential for respiration and mastication, yet we lack basic information on the anatomical organization underlying human tongue movement. Here we use microdissection, acetylcholinesterase histochemistry, silver staining of nerves, alpha bungarotoxin binding and immunohistochemistry to describe muscle fiber architecture and motor endplate (MEP) distribution of the human superior longitudinalis muscle (SL). The human SL extends from tongue base to tongue tip and is composed of fiber bundles that range from 2.8 to 15.7 mm in length. Individual muscle fibers of the SL range from 1.2 to 17.3 mm in length (1.3–18.2% of muscle length). Seventy-one percent of SL fibers have blunt-blunt terminations; the remainder have blunt-taper terminations. Multiple MEPs are present along SL length and dual MEPs are present on some muscle fibers. These data demonstrate that the human SL is a muscle of ‘in-series’ design. We suggest that SL motor units are organized to innervate specific regions of the tongue body and that activation of SL motor units according to anteroposterior location is one strategy employed by the nervous system to control tongue shape and tongue movement.
159 Background: Prior studies in GC patients have described predictors of inpatient palliative care (PC) consultation, but predictors of outpatient SPC consultation have not been elucidated. We sought to identify factors predictive of referral and associated care outcomes. Methods: We performed a cross-sectional study of GC patients seen in the gynecologic oncology clinic at a comprehensive cancer center over a three month period. As a part of routine care, patients completed a symptom questionnaire. Patients previously seen at the outpatient PC clinic were compared to those who had not with respect to demographics, disease characteristics, symptom scores, and provider factors using univariate statistics. A multivariate model was created to identify independent predictors of referral. Results: 913 patients completed the symptom survey. 76 patients (8%) had been seen in the outpatient PC clinic. Disease factors associated with referral included site (p < 0.01), stage (p < 0.01), evidence of disease (p < 0.01), active treatment (p < 0.01), and time point in the disease trajectory (p < 0.01). Women with moderate to severe pain (p < 0.01), sadness (p = 0.03), distress (p < 0.01), fatigue (p < 0.01), neuropathy (p = 0.03), and sexual dysfunction (p < 0.01) were more likely to have seen PC. Marital status, number of symptoms, and patient provider were also predictive of referral (all p < 0.01). In a multivariate model, site, stage, number of symptoms, moderate to severe sexual dysfunction, and provider were independently associated with referral. Compared to women who had not been referred, patients seen in the PC clinic were more likely to have a health care proxy documented in the electronic medical record (p < 0.01). Among patients with related symptoms, patients referred to PC more often had an opioid prescribed for pain (p < 0.01) and medications prescribed for depression (p < 0.01), anxiety (p = 0.04), insomnia (p < 0.01), and fatigue (p < 0.01). Conclusions: Women with depression, anxiety, insomnia, and fatigue were more likely to receive pharmacologic treatment for these symptoms from a SPC provider. Future research should identify referral triggers for those patients most likely to benefit from outpatient SPC consultation.
