Chemotherapy-induced pain is promoted by enhanced spinal adenosine kinase levels through astrocyte-dependent mechanisms

Development of chemotherapy-induced neuropathic pain (CINP) compromises the use of chemotherapy and greatly impacts thousands of lives. Unfortunately, there are no Food and Drug Administration–approved drugs to prevent or treat CINP. Neuropathological changes within CNS, including neuroinflammation and increased neuronal excitability, are driven by alterations in neuro-glia communication; but, the molecular signaling pathways remain largely unexplored. Adenosine is a potent neuroprotective purine nucleoside released to counteract the consequences of these neuropathological changes. Adenosine signaling at its adenosine receptors (ARs) is dictated by adenosine kinase (ADK) in astrocytes, which provides a cellular sink for the removal of extracellular adenosine. We now demonstrate that chemotherapy (oxaliplatin) in rodents caused ADK overexpression in reactive astrocytes and reduced adenosine signaling at the A3AR subtype (A3AR) within the spinal cord. Dysregulation of ADK and A3AR signaling was associated with increased proinflammatory and neuroexcitatory interleukin-1β expression and activation of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome, but not putative oxaliplatin-associated GSK3β transcriptional regulation. Intrathecal administration of the highly selective A3AR agonist MRS5698 attenuated IL-1β production and increased the expression of potent anti-inflammatory and neuroprotective IL-10. The effects of MRS5698 were...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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CONCLUSIONS: To our knowledge, this is the first documented case of gastropharyngeal anastomotic leak related to TKI use. A causal relationship is highly plausible given the previously stable anastomosis and the suspicious advent of complications within months of initiation of this new drug. While previously limited to cases of intraabdominal bowel dehiscence, this report now suggests that wound dehiscence must be considered a known side effect of TKIs throughout the gastrointestinal tract, including the gastropharynx. As such, the risk of anastomotic dehiscence should be discussed with the patient prior to starting a TKI....
Source: The Annals of Otology, Rhinology, and Laryngology - Category: ENT & OMF Authors: Tags: Ann Otol Rhinol Laryngol Source Type: research
In conclusion, this study suggests that epigenetic age acceleration is significantly associated with lung function in women older than 50 years. We hypothesised that this could be due to menopause. However, we have observed that menopause has minimal effect and therefore there is possibility of other unknown physiological factors at older age in females mediating the epigenetic age acceleration effect on lung function. While, it is still unknown what exactly epigenetic aging from DNA methylation measures, this study suggests it can be utilised as one of the important factors to assess women's lung health in old age. DNA me...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
A 44-year-old woman presented with lumbar pain (visual analog scale [VAS]  = 9) secondary to adrenocortical carcinoma sclerotic L4-vertebral metastasis. The positron emission tomography-computed tomography hypermetabolic lesion (Fig 1a,d) was unresponsive to radiotherapy or chemotherapy. She refused surgery. Following general anesthesia and aseptic preparation, 2 power d rill-mounted (Aesculap, Center Valley, Pennsylvania) k-wires were inserted in each vertebral pedicle with lateromedial opposite directions, resulting in crossed wires.
Source: Journal of Vascular and Interventional Radiology : JVIR - Category: Radiology Authors: Tags: Extreme IR Source Type: research
AbstractThe immunoglobulin (Ig) D type is a rare variant of multiple myeloma (MM), that accounts for 1 –2% of all cases. Compared to the more common types of MM, IgD MM is known to have more severe symptoms at presentation, and a poorer prognosis. A woman was admitted to our hospital for severe acute kidney disease and disorder (AKD) and back pain, and was started on hemodialysis. The renal biopsy revealed light chain cast nephropathy. She was diagnosed with IgD-λ MM based on Bence-Jones protein expression and high IgD serum levels, and started bortezomib therapy with plasma exchange (PE). After three sessions...
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
AbstractBackgroundPrognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors.MethodsFrom 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included i...
Source: World Journal of Surgery - Category: Surgery Source Type: research
Rationale: Diagnosing and treating refractory cancer pain have become standardized and effective procedures with guidance from the Expert Consensus on Refractory Cancer Pain released in 2017 by the Committee of Rehabilitation and Palliative Care of China. Doxorubicin has been used for perineural injection in the treatment of chronic non-cancer pain owing to its retrograde sensory ganglion resection effect. Our study reports a new fourth-ladder treatment for cancer pain: CT-guided paravertebral doxorubicin injection for patients with refractory cancer pain caused by paraspinal metastasis. Patient concerns: A 48-year-ol...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Rationale: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before. Patient concerns: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams i...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
This study presents the effects of berberine (BBR) on the aging process resulting in a promising extension of lifespan in model organisms. BBR extended the replicative lifespan, improved the morphology, and boosted rejuvenation markers of replicative senescence in human fetal lung diploid fibroblasts. BBR also rescued senescent cells with late population doubling (PD). Furthermore, the senescence-associated β-galactosidase (SA-β-gal)-positive cell rates of late PD cells grown in the BBR-containing medium were ~72% lower than those of control cells, and its morphology resembled that of young cells. Mechanistically...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Chemotherapy-induced neuropathic pain (CINP) in both sexes compromises many current chemotherapeutics and lacks an FDA-approved therapy. We recently identified the sphingosine-1-phosphate receptor subtype 1 (S1PR1) and A3 adenosine receptor subtype (A3AR) as novel targets for therapeutic intervention. Our work in male rodents using paclitaxel, oxaliplatin, and bortezomib showed robust inhibition of CINP with either S1PR1 antagonists or A3AR agonists. The S1PR1 functional antagonist FTY720 (Gilenya) is FDA-approved for treating multiple sclerosis, and selective A3AR agonists are in advanced clinical trials for cancer and in...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Publication date: Available online 14 December 2019Source: Urology Case ReportsAuthor(s): Ryuta Sato, Takahiro Ishikawa, Masaharu Imagawa, Hirotoshi Yonemasu, Takahiro Narimatsu, Kan MurakamiAbstractSmall cell carcinoma in the ureter is extremely rare, with few cases reported in the literature. The current report describes the case of a 63-year-old man who presented with right-side back pain. A mass was identified in the right ureter. A nephroureterectomy was performed. Subsequent microscopic examination revealed that the mass comprised a monotonous population of small cells and that the carcinoma cells were positive for c...
Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
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