Painful neuropathy is the principal dose-limiting factor in chemotherapy with vincristine, bortezomib, and thalidomide. This pain is refractory to treatment and often persists in cancer survivors. The long-term goal of this project is to determine the mechanism of chemotherapy-induced pain and identify potential therapeutic interventions for its relief and prevention. Several key tenets of a working model of chemoneuropathy will be tested in three specific aims conducted in humans who are undergoing chemotherapy for multiple myeloma or acute leukemia and/or in tumor-free animals treated with one of the same compounds.
Specific Aim i will test the hypothesis that vincristine, bortezomib and thalidomide induce or unmask elevated levels of proinflammatory cytokines and increased levels of activated NF-KB.
Specific Aim 2 will test the hypothesis that vincristine, bortezomib and thalidomide have shared effects on primary afferent fibers leading to neuropathic pain.
Specific Aim 3 will test the hypothesis that chemotherapy-induced neuropathy is produced by the action of pro-inflammatory cytokines in specific body compartments. This will be tested in humans and animals. In summary this project will define mechanisms of chemotherapy-induced pain, identify near-term treatment candidates, and establish the key databases needed to design and justify clinical trials that will be the subject of follow-up studies. This project will provide direct evidence for several important basic tenets of a pathophysiological model of chemo-neuropathy that in turn will define important new targets for therapy and intervention. This project will therefore impact on the quality of life, survival and the return to productivity of nearly all cancer patients who receive vincristine, thalidomide or bortezomib.
|Shah, Nina; Shi, Qiuling; Giralt, Sergio et al. (2018) Utility of a patient-reported outcome in measuring functional impairment during autologous stem cell transplant in patients with multiple myeloma. Qual Life Res 27:979-985|
|Hansen, Chase C; Smith, Joshua B; Mohamed, Abdallah S R et al. (2017) Cognitive function and patient-reported memory problems after radiotherapy for cancers at the skull base: A cross-sectional survivorship study using the Telephone Interview for Cognitive Status and the MD Anderson Symptom Inventory-Head and Neck Module. Head Neck 39:2048-2056|
|Shah, Nina; Shi, Qiuling; Williams, Loretta A et al. (2016) Higher Stem Cell Dose Infusion after Intensive Chemotherapy Does Not Improve Symptom Burden in Older Patients with Multiple Myeloma and Amyloidosis. Biol Blood Marrow Transplant 22:226-231|
|Colvin, L A; Dougherty, P M (2015) Peripheral neuropathic pain: signs, symptoms, mechanisms, and causes: are they linked? Br J Anaesth 114:361-3|
|Xu, Yichen; Chen, Yanzhi; Li, Pingping et al. (2015) Ren Shen Yangrong Tang for Fatigue in Cancer Survivors: A Phase I/II Open-Label Study. J Altern Complement Med 21:281-7|
|Shi, Qiuling; Wang, Xin Shelley; Li, Guojun et al. (2015) Racial/ethnic disparities in inflammatory gene single-nucleotide polymorphisms as predictors of a high risk for symptom burden in patients with multiple myeloma 1 year after diagnosis. Cancer 121:1138-46|
|Gunn, G Brandon; Hansen, Chase C; Garden, Adam S et al. (2015) Favorable patient reported outcomes following IMRT for early carcinomas of the tonsillar fossa: Results from a symptom assessment study. Radiother Oncol 117:132-8|
|Mendoza, Tito R; Wang, Xin Shelley; Williams, Loretta A et al. (2015) Measuring Therapy-Induced Peripheral Neuropathy: Preliminary Development and Validation of the Treatment-Induced Neuropathy Assessment Scale. J Pain 16:1032-43|
|Wang, Xin Shelley; Shi, Qiuling; Williams, Loretta A et al. (2015) Longitudinal analysis of patient-reported symptoms post-autologous stem cell transplant and their relationship to inflammation in patients with multiple myeloma. Leuk Lymphoma 56:1335-41|
|Robinson, C R; Dougherty, P M (2015) Spinal astrocyte gap junction and glutamate transporter expression contributes to a rat model of bortezomib-induced peripheral neuropathy. Neuroscience 285:1-10|
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