Reasons for breast cancer heterogeneity

Breast cancers differ in many ways, such as in their cell of origin, the molecular alterations causing them and the susceptibility and defenses of the patient, and this makes it difficult to give the most appropriate treatment. Two recent papers have contributed to the establishment of a more precise molecular classification of breast tumors

Unmasking of myoclonus by lacosamide in generalized epilepsy

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, in some individuals with genetic generalized epilepsy (GGE)

A reason why the ERBB2 gene is amplified and not mutated in breast cancer

Alterations of receptor-type tyrosine kinases (RTK) are frequent in human cancers. They can result from translocation, mutation or amplification. The ERBB2 RTK is encoded by a gene that is amplified in about 20% breast cancers. The question is: why is this RTK specifically subjected to this type of alteration? We propose that ERBB2 gene amplification is used to overcome repression of its expression by sequence-specific transcription factors

Transfer of a Polaritonic Qubit through a Coupled Cavity Array

We demonstrate a scheme for quantum communication between the ends of an array of coupled cavities. Each cavity is doped with a single two level system (atoms or quantum dots) and the detuning of the atomic level spacing and photonic frequency is appropriately tuned to achieve photon blockade in the array. We show that in such a regime, the array can simulate a dual rail quantum state transfer protocol where the arrival of quantum information at the receiving cavity is heralded through a fluorescence measurement. Communication is also possible between any pair of cavities of a network of connected cavities.Comment: Contribution to Special Issue in Journal of Modern Optics celebrating the 60th birthday of Peter L. Knigh

“Stealth” tumors: Breast cancer cells shun NK-cells anti-tumor immunity

Breast cancers (BCs) comprise heterogeneous subtypes of various prognoses. An active anti-tumor immune profile usually correlated with a better survival. Two current major challenges of BC research are to understand the inter-relations between BC and anti-tumor immunity, and to identify candidates whose targeting would contribute to enhance anti-tumor efficiency

Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cγ at the centrosome

<p>Abstract</p> <p>Background</p> <p>The t(6;8) translocation found in rare and agressive myeloproliferative disorders results in a chimeric gene encoding the FOP-FGFR1 fusion protein. This protein comprises the N-terminal region of the centrosomal protein FOP and the tyrosine kinase of the FGFR1 receptor. FOP-FGFR1 is localized at the centrosome where it exerts a constitutive kinase activity.</p> <p>Results</p> <p>We show that FOP-FGFR1 interacts with the large centrosomal protein CAP350 and that CAP350 is necessary for FOP-FGFR1 localisation at centrosome. FOP-FGFR1 activates the phosphoinositide-3 kinase (PI3K) pathway. We show that p85 interacts with tyrosine 475 of FOP-FGFR1, which is located in a YXXM consensus binding sequence for an SH2 domain of p85. This interaction is in part responsible for PI3K activation. Ba/F3 cells that express FOP-FGFR1 mutated at tyrosine 475 have reduced proliferative ability. Treatment with PI3K pathway inhibitors induces death of FOP-FGFR1 expressing cells. FOP-FGFR1 also recruits phospholipase Cγ1 (PLCγ1) at the centrosome. We show that this enzyme is recruited by FOP-FGFR1 at the centrosome during interphase.</p> <p>Conclusion</p> <p>These results delineate a particular type of oncogenic mechanism by which an ectopic kinase recruits its substrates at the centrosome whence unappropriate signaling induces continuous cell growth and MPD.</p

The IUSM Scholarly Concentrations Program: Strategic Collaborative Education Across Schools and Departments

Presented as a poster at 2020 IUSM Education Day.A changing healthcare landscape calls for innovation and expansion of expertise in medical education. How does a medical school better prepare medical students to thrive in a changing profession? Through its Scholarly Concentrations Program, Indiana University School of Medicine is collaborating with non-physician experts from schools with expertise in topics that are medically relevant and of interest to medical students. Scholarly Concentrations are longitudinal experiences that enhance the medical education program through coursework and scholarly work. In addition to enhancing students’ education, it offers the opportunity to enhance campus reputation and develop research focus for students and faculty. Partnerships were created in both directions. IU School of Medicine sought out schools and departments with unique expertise on different medical campuses. Schools and departments also approached IU School of Medicine about its Scholarly Concentrations program as momentum built. These partnerships are creating mutual benefits for IUSM, partners, faculty and students. Benefits for partner organizations include mentoring opportunities, reputational enhancement, having an impact on healthcare system, and pathways to certificates and advanced degrees. For IUSM and its students, the partnerships enhance professional development through Scholarly Concentrations in areas of clinical, teaching, research, advocacy and administration

Educational Programs and Adaptability: A Systems Approach to Creating Adaptable Educational Programs

The IUSM Scholarly Concentrations Program is an optional four-year longitudinal program that allows students to explore interests outside the core medical curriculum. In two years, 17 concentrations were developed statewide and more than 220 students enrolled. As a part of developing a sustainable educational program, a Plan-Do-Check-Act improvement cycle is being used. This workshop will feature examples of the use of the Plan-Do-Check-Act improvement cycle during the launch and pilot a large, novel educational program that is “good enough” and builds toward sustainability and excellence while responding to large-scale systematic changes. Participants in the workshop will apply these principles to their own educational programs

Risky decision making : testing for violations of transitivity predicted by an editing mechanism

Transitivity is the assumption that if a person prefers A to B and B to C, then that person should prefer A to C. This article explores a paradigm in which Birnbaum, Patton and Lott (1999) thought people might be systematically intransitive. Many undergraduates choose C = ($96, .85;$90, .05; $12, .10) over A = ($96, .9; $14, .05;$12, .05), violating dominance. Perhaps people would detect dominance in simpler choices, such as A versus B = ($96, .9;$12, .10) and B versus C, and yet continue to violate it in the choice between A and C, which would violate transitivity. In this study we apply a true and error model to test intransitive preferences predicted by a partially effective editing mechanism. The results replicated previous findings quite well; however, the true and error model indicated that very few, if any, participants exhibited true intransitive preferences. In addition, violations of stochastic dominance showed a strong and systematic decrease in prevalence over time and viola

Basal Breast Cancer: A Complex and Deadly Molecular Subtype

During the last decade, gene expression profiling of breast cancer has revealed the existence of five molecular subtypes and allowed the establishment of a new classification. The basal subtype, which represents 15-25% of cases, is characterized by an expression profile similar to that of myoepithelial normal mammary cells. Basal tumors are frequently assimilated to triple-negative (TN) breast cancers. They display epidemiological and clinico-pathological features distinct from other subtypes. Their pattern of relapse is characterized by frequent and early relapses and visceral locations. Despite a relative sensitivity to chemotherapy, the prognosis is poor. Recent characterization of their molecular features, such as the dysfunction of the BRCA1 pathway or the frequent expression of EGFR, provides opportunities for optimizing the systemic treatment. Several clinical trials dedicated to basal or TN tumors are testing cytotoxic agents and/or molecularly targeted therapies. This review summarizes the current state of knowledge of this aggressive and hard-to-treat subtype of breast cancer