Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.

Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib. Exp Neurol. 2017 Jul 18;296:74-82 Authors: Wei JY, Liu CC, Ouyang HD, Ma C, Xie MX, Liu M, Lei WL, Ding HH, Wu SL, Xin WJ Abstract Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats. Spinal local application of methylglyoxal also induced mechanical allodynia and central sensitization in normal rats. Moreover, administration of bortezomib upregulated the expression of receptors for advanced glycation end products (RAGE) and phosphorylated STAT3 (p-STAT3) in dorsal horn. Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregula...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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Stefano and I returned from England almost a week ago, last Saturday evening, but since then I’ve had a million things to do, not just heaps of laundry, food shopping, and the usual household-related stuff (cat litter, cat this, cat that, cat everything!), but also getting together with my girlfriends, a very important part of my life!, AND planning my English lessons for next week. I still  need to fit my sessions at the rehab center into my weekly schedule. These are the workouts I still need to do both for my shoulder AND for my tendinitis, which actually behaved incredibly well after the first week or so on ...
Source: Margaret's Corner - Category: Cancer & Oncology Authors: Tags: Blogroll Lake District Peak District Sandsend Shambles Straithes Whitby York Source Type: blogs
Conclusion: This retrospective series of patients treated with palliative intent for multiple myeloma using various dose and fractionation schemes showed favorable symptomatic relieve in most patients. Radiographic response did not correlate with clinical response with fewer patients having radiologic disease regression. Longer follow-up is necessary to determine if the lack of radiologic response is associated with clinically relevant recurrent pain.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionThis case demonstrates that sternoclavicular joint arthropathy results in symptoms that can mimic the presenting symptoms of shoulder or cervical spine pathology, such as shoulder and neck pain, necessitating careful diagnosis and management.
Source: Interdisciplinary Neurosurgery - Category: Neurosurgery Source Type: research
Conclusion: CEACAM6 plasma levels can noninvasively identify pts. with a plasma cell disorder and should be evaluated prospectively as a potential diagnostic marker. Moreover, due to high CEACAM6 levels in the bone marrow in RRMM pts., this adhesion molecule might be a therapeutic target in multiple myeloma pts. PMID: 30809317 [PubMed - in process]
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases.MethodsThis single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or u...
Source: Trials - Category: Research Source Type: clinical trials
Authors: Wildes TM, Anderson KC Abstract Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. The pain limits her exercise tolerance such that she can now walk only 1 block. She is a retired schoolteacher who does volunteer efforts in her community but has limited her activities due to fatigue. Karnofsky performance status is 70%. She has a history of chronic hypertension treated with a diuretic, adult-onset diabetes mellitus treated with metformin, and hypothyroidism treated with levothyroxine. Initial evaluation reveals anemia, renal dysfunction, an elevated ...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Facon T, Anderson K Abstract Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. The pain limits her exercise tolerance such that she can now walk only 1 block. She is a retired schoolteacher who does volunteer efforts in her community but has limited her activities due to fatigue. Karnofsky performance status is 70%. She has a history of chronic hypertension treated with a diuretic, adult-onset diabetes mellitus treated with metformin, and hypothyroidism treated with levothyroxine. Initial evaluation reveals anemia, renal dysfunction, an elevated tot...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Leukemia relapse occurring in donor cells, so called donor cell leukemia (DCL) after allogeneic hematopoietic stem cell transplantation has been previously reported in the literature. Some authors have suggested that the development of DCL is perhaps a more common occurrence than traditionally thought. Donor cell myeloma (DCM) seems to be less frequent than DCL. This 46-year old male when first seen in 2000 was diagnosed with stage IIIa multiple myeloma. A monoclonal IgA kappa spike was recorded at diagnosis. Treatment with melphalan and prednisone was delivered every four to six weeks for a total of 22 courses. Fourty mon...
Source: Blood - Category: Hematology Authors: Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation: Novel Antibody Combinations in Myeloma Source Type: research
We examined factors associated with upfront RT in a multivariable logistic model. We then examined the association between upfront RT and overall survival (OS) in a proportional hazard model adjusting for age, sex, race, income, insurance status, comorbidity index, year of diagnosis, type of treating hospital, and time from diagnosis to start of therapy.ResultsOf the 88,995 patients with myeloma, 15,223 (18%) received upfront RT, at median 15 days from diagnosis. Median radiation dose was 3000 cGy delivered over median 10 fractions, with the most common targets being spine/skull (59%), hips/pelvis (12%), and other bones (1...
Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster II Source Type: research
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