Colorectal carcinoma progression is not influenced by the pseudokinase PEAK1.

The scaffold protein PEAK1 acts downstream of integrin adhesion complexes and the epidermal growth factor receptor, orchestrating signaling events that control cell proliferation and cytoskeletal remodeling. In this study we investigated the role of PEAK1 in colorectal carcinoma (CRC) progression using various in vitro and in vivo models to replicate the stepwise pathogenesis of CRC. While we observed a cell-type specific role for PEAK1 in the proliferation and in human CRC cell lines in vitro, our in vivo experiments using different CRC mouse models driven by loss of Apc, with or without oncogenic Kras or Pten loss suggest that PEAK1 does not significantly contribute to tumor formation in vivo.

The case for therapeutic overactivation of oncogenic signaling as a potential cancer treatment strategy.

Most targeted cancer drugs inhibit the oncogenic signals to which cancer cells are addicted. We discuss here a counterintuitive approach to cancer therapy, which consists of deliberate overactivation of the oncogenic signals to overload the stress responses of cancer cells. We discuss why such overactivation of oncogenic signaling, combined with perturbation of the stress response pathways, can be potentially effective in killing cancer cells, aiming to inspire further discussion and consideration.

The phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing.

Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology.

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells.

Impact of Brushing Protocols on Dentin Abrasion Caused by Different Abrasive Slurries.

Purpose: To determine the impact of the brushing protocol on dentin wear by comparing continuous to intermittent brushing, with the same total time of brushing.

Materials And Methods: Dentin specimens (n = 120) were evently distributed into six groups (A-F). The samples were brushed with slurries of different relative dentin abrasivity (RDA): Groups A+B (Sident 2480-1; RDA 85), groups C+D (Zeodent 113; RDA 67), and groups E+F (Zeodent 103; RDA 174).

Associations between tooth wear and dental sleep disorders: A narrative overview.

Objectives: Tooth wear is a common finding in adult patients with dental sleep disorders. The aim of this paper was to review the literature on the possible associations between tooth wear and the following dental sleep disorders: sleep-related oro-facial pain, oral moistening disorders, gastroesophageal reflux disease (GERD), obstructive sleep apnoea syndrome (OSAS) and sleep bruxism.

Methods: A PubMed search was performed on 1 June 2018 using MeSH terms in the following query: Tooth Wear AND (Facial Pain OR Temporomandibular Joint Disorders OR Xerostomia OR Sialorrhea OR Gastroesophageal Reflux OR Sleep Apnea Syndrome OR Sleep Bruxism).

Oral health-related quality of life in patients with tooth wear.

The aim of this study was to investigate the impact of tooth wear (TW) on patients' oral health-related quality of life. A total of 198 participants were included in the study. They belonged to the following four different diagnostic categories: 51 patients with TW, 46 patients with painful temporomandibular disorders (TMD), 43 complete denture wearers and 58 healthy controls.

[Oral kinesiology and the quality of life].

In a comparative study, the influence of oral health on the quality of life was investigated for people with temporomandibular pain, people with tooth wear and people with complete dentures. To this end, the study made use of the Oral Health Impact Profile. Both the total score and the scores on 4 of the 7 domains of the Oral Health Impact Profile were significantly higher in the research group with temporomandibular pain than in the research groups with tooth wear and complete dentures.

Efficacy and safety of aztreonam in the treatment of patients with renal failure.

The efficacy and safety of aztreonam for treatment of gram-negative bacterial infections in patients with renal failure were evaluated in an open study. Thirty-nine patients (22-82 years old) with renal failure (chronic, 25; acute, 14) were treated for 40 severe gram-negative bacterial infections. All 41 gram-negative pathogens isolated were sensitive to aztreonam; the pathogens included Escherichia coli (12), Pseudomonas aeruginosa (8), Klebsiella species (7), Proteus species (7), Enterobacter species (5), Serratia marcescens (1), and Acinetobacter species (1).