Cost-Effective, Commercial Scale Production of Tanespimycin

Recent approaches to cancer therapy have centered on developing small molecule inhibitors for signaling pathways deranged in common cancers; these compounds are sometimes referred to as tumor antibiotics. One promising target for tumor antibiotics is Hsp90, a heat shock protein that plays a central role in promoting the functionality and stability of a group of proteins associated with cancer called client proteins. Hsp90 inhibitors have been receiving extensive research attention, with geldanamycin, tanespimycin, and their derivatives at the forefront. This report describes a novel, cost-effective, commercial scale process design for the production of tanespimycin. The proposed production facility is designed to deliver 1,084 kg/year through 55 batches, requiring operation of 293 days/year. Detailed economic analysis suggest the recuperation of funds after an initial investment into the biopharmaceutical plant and Phase III trials, which suggest that further investment in this process design would be highly profitable

2004-2005 Young Musicians Competition - Strings

Coordinator Sergiu Schwartz, Lynn University Conservatory of Music Accompanist Tao Lin, Lynn University Conservatory of Music Judges Jody Atwood, cello - American String Teachers Association, Florida Chapter Shigeru Ishikawa, double-bass - Lynn University Conservatory of Music Marcia Littley de Arias, violin - Artist-in-Residence, Florida International University and Amernet String Quartethttps://spiral.lynn.edu/conservatory_other-competitions/1002/thumbnail.jp

2002-2003 Florida\u27s Young Musician Showcase

https://spiral.lynn.edu/conservatory_otherseasonalconcerts/1090/thumbnail.jp

Combined treatment of adenoid cystic carcinoma with cetuximab and IMRT plus C12 heavy ion boost: ACCEPT [ACC, Erbitux® and particle therapy]

<p>Abstract</p> <p>Background</p> <p>Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent leading to the establishment of particle therapy in this indication. However, even modern techniques leave space for improvement of local control by intensification of local treatment. Radiation sensitization by exploitation of high EGFR-expression in ACC with the EGFR receptor antibody cetuximab seems promising.</p> <p>Methods/design</p> <p>The ACCEPT trial is a prospective, mono-centric, phase I/II trial evaluating toxicity (primary endpoint: acute and late effects) and efficacy (secondary endpoint: local control, distant control, disease-free survival, overall survival) of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 49 patients with histologically proven (≥R1-resected, inoperable or Pn+) ACC. Patients receive 18 GyE carbon ions (6 fractions) and 54 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy.</p> <p>Discussion</p> <p>The primary objective of ACCEPT is to evaluate toxicity and feasibility of cetuximab and particle therapy in adenoid cystic carcinoma.</p> <p>Trial Registration</p> <p>Clinical Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01192087">NCT 01192087</a></p> <p>EudraCT number: 2010 - 022425 - 15</p

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

<p>Abstract</p> <p>Background</p> <p>Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab.</p> <p>Methods</p> <p>Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation.</p> <p>Results</p> <p>Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively.</p> <p>Conclusion</p> <p>While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial.</p

Point-of-care Ultrasound Diagnosis of Pulmonary Hydatid Cyst Disease Causing Shock: A Case Report

Introduction: Point-of-care ultrasound (POCUS) is accepted as an important tool for evaluatingpatients presenting to the emergency department (ED) with dyspnea1 and undifferentiated shock.2Identifying the etiology and type of shock is time-critical since treatments vary based on thisinformation. Clinicians typically rely on the history, exam, and diagnostics tests to identify theetiology of shock. In resource-limited settings where there is reduced access to timely laboratory anddiagnostic studies. The use of POCUS enables rapid classification and directed treatment of shock.Additionally, POCUS can aid in the diagnosis of rarer tropical diseases that can be important causesof shock in resource-limited settings.Case Report: We discuss a case of a pediatric patient who presented to an ED in Cusco, Peru, withacute dyspnea and shock. Point-of-care ultrasound was used to expedite the diagnosis of a rupturedpulmonary hydatid cyst, guide proper management of septic and anaphylactic shock, and expeditedefinitive surgical intervention.Conclusion: In resource-limited settings where there is reduced access to timely laboratory anddiagnostic studies, the use of POCUS enables rapid classification and directed treatment of shock

Toward improvement of knowledge of financial conflicts of interest in a large medical school in France.

IntroductionConflict of interests (COIs) adversely affect the integrity of science and public health. The role of medical schools in the teaching and management of COIs has been highlighted by the publication of an annual evaluation of American medical schools based on their COIs policies by the American Medical Student Association (AMSA). A deontological charter was adopted by French medical schools in 2018 but its impact on COI comprehension by students and its effects on COI prevention were not evaluated.MethodsA 10-item direct survey was conducted among about 1000 students in Paris-Cité University in order to investigate the respect of the charter regarding COIs both in the medical school and in affiliated teaching hospitals.ResultsCumulative results show a satisfying respect of prevention policies regarding COIs in the medical school and hospitals despite the fact that the existence of the charter and its major aspects were insufficiently known. Disclosure of COIs by teachers was insufficient.ConclusionThis first direct study among students shows better results than expected according to current non-academic surveys. Moreover, this study demonstrates the feasibility of this kind of survey whose repetition should be an appropriate tool to improve the implementation of the charter within medical schools and teaching hospitals, in particular mandatory disclosure of COIs by teachers

Proton Reirradiation for Locoregionally Recurrent Breast Cancer

Purpose: Local-regional recurrence (LRR) of breast cancer after prior adjuvant radiation (RT) can present a clinical challenge. Proton therapy is recommended by the American Society for Radiation Oncology in cases where reirrradiation is needed; however, data are limited. We present the toxicity and outcomes after reirradiation for local-regional recurrence of breast cancer with proton therapy. Methods and Materials: A single-institution retrospective review identified patients with the following criteria: LRR of breast cancer, prior photon radiation to the same region, proton beam reirradiation, and definitive intent. Surgery or systemic therapy at the time of recurrence was used when indicated. The log-rank test was used to compare Kaplan-Meier survival estimates. Kruskal-Wallis tests were performed to compare worst reported toxicities with clinical variables. Results: The population included 27 patients with a history of prior radiation and treated with proton therapy for LRR between 2012 and 2019. The median interval between courses was 9.7 years. Proton reirradiation regimens included whole breast/chest wall (WB/CW) with regional nodal RT (22/27), nodal RT alone (2/27), or WB/CW alone (3/27). The median dose was 51 Gy, and the most common fractionation was 1.5 Gy twice daily. Median follow-up after reirradiation was 16.6 months. Acute grade 3 toxicities included dermatitis in 2 patients and breast pain in 2 patients. Grade 2 or higher late toxicities included 6 G2 rib fractures and 1 G2 brachial plexopathy, 1 G3 dermatitis, 1 G3 breast pain, and 1 G4 dermatitis. Twelve patients had new documented recurrences of which 1 was a second in-field LRR, and there were 7 deaths. Conclusions: Proton salvage reirradiation to median 51 Gy in 1.5 Gy twice daily appears to be safe with acceptable acute and late toxicity, and effective with >95% local-regional control

Teens Impulsively React rather than Retreat from Threat

There is a significant inflection in risk taking and criminal behavior during adolescence, but the basis for this increase remains largely unknown. An increased sensitivity to rewards has been suggested to explain these behaviors, yet juvenile offences often occur in emotionally charged situations of negative valence. How behavior is altered by changes in negative emotional processes during adolescence has received less attention than changes in positive emotional processes. The current study uses a measure of impulsivity in combination with cues that signal threat or safety to assess developmental changes in emotional responses to threat cues. We show that adolescents, especially males, impulsively react to threat cues relative to neutral ones more than adults or children, even when instructed not to respond. This adolescent-specific behavioral pattern is paralleled by enhanced activity in limbic cortical regions implicated in the detection and assignment of emotional value to inputs and in the subsequent regulation of responses to them when successfully suppressing impulsive responses to threat cues. In contrast, prefrontal control regions implicated in detecting and resolving competing responses show an adolescent-emergent pattern (i.e. greater activity in adolescents and adults relative to children) during successful suppression of a response regardless of emotion. Our findings suggest that adolescence is a period of heightened sensitivity to social and emotional cues that results in diminished regulation of behavior in their presence.Psycholog