Thyrotropin-Releasing Hormone Can Relieve Cancer-Related Fatigue: Hypothesis and Preliminary Observations

Fatigue in cancer patients is highly prevalent, predominantly idiopathic, difficult to manage, and has a significant negative impact on quality of life. Thyrotropin-releasing hormone (TRH) exerts normotrophic, state-dependent therapeutic effects in a variety of experimental and clinical situations. To evaluate TRH as a treatment for cancer-related fatigue, an ongoing randomized, placebo-controlled, crossover pilot study of breast cancer patients has been initiated and this report presents preliminary observations conducted with three of these patients over 4 consecutive weeks, thereby involving a total of six TRH treatments and six saline controls. Global assessment using both subjective and objective parameters showed that TRH exerted clear anti-fatigue effects in four of the six TRH treatments. These responses were rapid in onset and persisted through the 24 h observation period. No anti-fatigue responses were seen in five of the six saline controls. No unexpected side-effects were seen with TRH administration. These initial findings support the proposal that TRH can ameliorate cancer-related fatigue

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field

Development of pseudosubstrate-based peptide and peptidomimetic inhibitors of p60ᶜ⁻ˢʳᶜ protein tyrosine kinase using combinatorial chemistry technology

Several protein tyrosine kinases and the signaling pathways in which they participate have emerged as attractive targets for drug design. Specific and potent PTK inhibitors not only represent a new class of anticancer agents but may also be used as a powerful research tool to study the role of PTK-dependent cellular pathways in normal or tumor cell growth and to dissect the redundancy in signal transduction pathways. Dr. Lam's laboratory has previously reported identification of efficient and specific peptide substrates for p60ᶜ⁻ˢʳᶜ PTK using one-bead one-peptide combinatorial library method (Lam et al., 1995; Lou et al., 1996a and b). Based on the structure of these peptide substrates, I have identified and characterized potent and selective peptide inhibitors of p60ᶜ⁻ˢʳᶜ PTK. Some of the identified peptide inhibitors were used as a research tool in this dissertation to investigate the active site of the enzyme p60ᶜ⁻ˢʳᶜ PTK. In addition to potency and selectivity, a major criterion for a successful src inhibitor is its cell permeability as src is located inside the cell. Peptides are generally impermeable to cell membrane. A major accomplishment of this dissertation is development of cell permeable peptidomimetic inhibitors of p60ᶜ⁻ˢʳᶜ PTK based on the identified dipeptide motif --Ile-Tyr- (-I-Y-). This dissertation describes identification of tetrameric and trimeric peptidomimetic inhibitors using a combination of two combinatorial methods, the 'one-bead one-compound' combinatorial method and the 'iterative' combinatorial method. Some of the identified inhibitors seem to selectively affect transformed cells versus normal cells at lower concentrations. A lot of still needs to be done to optimize these inhibitors. However, the accomplished work in this dissertation proves the feasibility of the pseudosubstrate peptide-based approach for the development of cell permeable peptidomimetic inhibitors as anti-cancer therapeutic agents

Sleep Disturbances in Schizophrenia.

Sleep disturbances are prevalent in patients with schizophrenia and play a critical role in the morbidity and mortality associated with the illness. Subjective and objective assessments of sleep in patients with schizophrenia have identified certain consistent findings. Findings related to the sleep structure abnormalities have shown correlations with important clinical aspects of the illness. Disruption of specific neurotransmitter systems and dysregulation of clock genes may play a role in the pathophysiology of schizophrenia-related sleep disturbances. Antipsychotic medications play an important role in the treatment of sleep disturbances in these patients and have an impact on their sleep structure

Bayesian inference of temporal task specifications from demonstrations

Paper presented at the Annual Conference on Neural Information Processing Systems 2018 (NeurIPS 2018), 3-8 December 3-8, 2018, Montréal, Québec.When observing task demonstrations, human apprentices are able to identify whether a given task is executed correctly long before they gain expertise in actually performing that task. Prior research into learning from demonstrations (LfD) has failed to capture this notion of the acceptability of an execution; meanwhile, temporal logics provide a flexible language for expressing task specifications. Inspired by this, we present Bayesian specification inference, a probabilistic model for inferring task specification as a temporal logic formula. We incorporate methods from probabilistic programming to define our priors, along with a domain-independent likelihood function to enable sampling-based inference. We demonstrate the efficacy of our model for inferring specifications with over 90% similarity between the inferred specification and the ground truth, both within a synthetic domain and a real-world table setting task

The biology of cancer-related fatigue: a review of the literature

© 2015, Springer-Verlag Berlin Heidelberg (Outside the USA). Purpose: Understanding the etiology of cancer-related fatigue (CRF) is critical to identify targets to develop therapies to reduce CRF burden. The goal of this systematic review was to expand on the initial work by the National Cancer Institute CRF Working Group to understand the state of the science related to the biology of CRF and, specifically, to evaluate studies that examined the relationships between biomarkers and CRF and to develop an etiologic model of CRF to guide researchers on pathways to explore or therapeutic targets to investigate. Methods: This review was completed by the Multinational Association of Supportive Care in Cancer Fatigue Study Group–Biomarker Working Group. The initial search used three terms (biomarkers, fatigue, cancer), which yielded 11,129 articles. After removing duplicates, 9145 articles remained. Titles were assessed for the keywords “cancer” and “fatigue” resulting in 3811 articles. Articles published before 2010 and those with sample