11 research outputs found
Broad targeting of resistance to apoptosis in cancer
Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer
Resources Designed to Promote Professional Discourse
The Army provides its servicemembers with Army regulation, doctrinal, and organizational publications to accomplish essential tasks—from training and leading units to conducting military operations. Professional discourse is no exception. The US Army War College and Army University Press recently published resources to help the force prioritize professional discourse. These documents provide a starting point for aspiring researchers and a reference guide for individuals and organizations. Combined, these new publications will help the force to take up Chief of Staff of the Army Randy A. George’s charge to revitalize professional discourse in the Army
Professional Discourse Is Shaping the Force
The Army is transforming. While today’s senior leaders have set the service on a modernization path, future problems belong to the next generation—and we must own them. Professional writing is a way to do so, a tool enabling leaders of any rank to influence change at the macro level by contributing meaningfully to Department of Defense (DoD) conversations. Those embarking on this challenging adventure are not alone; writing is a team sport. The journey is as important as the destination, and most who take up this charge find participation in professional dialogue highly rewarding
LESSONS LEARNED AND UNLEARNED: U.S. FIELD ARTILLERY SINCE THE END OF WWII
This thesis examines the adaptation of U.S. indirect-fire capabilities since 1945, with reference to three potential drivers of military innovation: new technology, combat experience, and external threats. Throughout this period U.S. artillery platforms and munitions—alongside the maneuver forces they were designed to support—have grown in complexity, lethality, accuracy, range, and mobility. Current U.S. artillery munitions nevertheless lag behind those of other modern militaries in important respects, including target-seeking rounds and the destruction of armor. In addition, today’s artillery platforms—towed and self-propelled alike—are too slow for a high-tempo fight. Thus, although capabilities have developed dramatically, in a large-scale combat operation, modern U.S. artillery would likely play a minor role.
This thesis examines 70 years of artillery development, and concludes that apart from the immediate pressures of active conflict, external threats are the primary driver of adaptation. Thus, current and future projects are likely to revolve around a singular focus: preparing to combat a peer adversary. In this regard, this thesis offers developmental recommendations to help the artillery branch maintain its hard-won historical position as the King of Battle.Outstanding ThesisCaptain, United States ArmyApproved for public release. distribution is unlimite
Evaluation of survivin expression and its prognostic value in papillary thyroid carcinoma
The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target
Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features