Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional and anatomical relationships among primary afferent fibers, blood vessels, and cancers are poorly understood. However, recent evidence suggests that physical and biochemical interactions between these peripheral components are important to both tumor biology and cancer-associated pain. To determine the role of these peripheral components in a mouse model of cancer pain, we quantified the change in nerve and blood vessel density within a fibrosarcoma tumor mass using stereological analysis of serial confocal optical sections of immunostained hind paw. To this end we introduced the Discoma coral-derived red fluorescent protein (DsRed2) into the NCTC 2472 fibrosarcoma line using the Sleeping Beauty transposon methodology, thus providing a unique opportunity to visualize tumor-nerve-vessel associations in context with behavioral assessment of tumor-associated hyperalgesia. Tumors from hyperalgesic mice are more densely innervated with calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers and less densely vascularized than tumors from non-hyperalgesic mice. As hyperalgesia increased from Day 5 to 12 post-implantation, the density of protein gene product 9.5 (PGP9.5)-immunoreactive nerves and CD31-immunoreactive blood vessels in tumors decreased, whereas CGRP-immunoreactive nerve density remained unchanged. Importantly, intra-tumor injection of a CGRP1 receptor antagonist (CGRP 8-37) partially blocked the tumor-associated mechanical hyperalgesia, indicating that local production of CGRP may contribute to tumor-induced nociception through a receptor-mediated process. The results describe for the first time the interaction among sensory nerves, blood vessels and tumor cells in otherwise healthy tissue, and our assessment supports the hypothesis that direct tumor cell-axon communication may underlie, at least in part, the occurrence of cancer pain.
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PMID:Tumor-induced mechanical hyperalgesia involves CGRP receptors and altered innervation and vascularization of DsRed2 fluorescent hindpaw tumors. 1583 73

Cancer pain significantly affects the diagnosis, quality of life and survival of patients with cancer. During the past decade, preclinical and clinical data has begun to provide insight into the mechanisms that drive and mask cancer pain and the mechanisms by which anti-neoplastic agents induce peripheral neuropathy. Developing a mechanism-based understanding and mechanism-based therapies to treat cancer-associated pain and sensory neuropathy, and incorporating these into mainstream cancer research and therapy, will be crucial to improving the quality of life and survival of patients with cancer.
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PMID:Cancer pain and its impact on diagnosis, survival and quality of life. 1698 55

The mechanisms involved, and possible treatment targets, in orofacial pain due to cancer are poorly understood. The aim of the first of this two-part series is to review the involved pathophysiological mechanisms and explore their possible roles in the orofacial region. However, there is a lack of relevant research in the trigeminal region, and we have therefore applied data accumulated from experiments on cancer pain mechanisms in rodent spinal models. In the second part, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. In the present article, we provide a brief outline of trigeminal functional neuro-anatomy and pain-modulatory pathways. Tissue destruction by invasive tumors (or metastases) induces inflammation and nerve damage, with attendant acute pain. In some cases, chronic pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant, painful effects of tumors include paraneoplastic neuropathic syndromes and effects secondary to the release of factors by the tumor (growth factors, cytokines, and enzymes). Additionally, pain is frequent in cancer management protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms involved in cancer-related orofacial pain will enhance patient management.
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PMID:Orofacial pain in cancer: part I--mechanisms. 1752 48

Cancer-associated pain is extremely common and is associated with significant physical and psychological suffering. Unfortunately, pain associated with cancer or its treatment is frequently under-treated, probably due to several factors, including phobia of opioids, under-reporting by patients, and under-diagnosis by healthcare workers. The most common etiology of cancer pain is local tumor invasion (primary or metastatic), involving inflammatory and neuropathic mechanisms; these have been reviewed in Part I. As malignant disease advances, pain usually becomes more frequent and more intense. Additional expressions of orofacial cancer pain include distant tumor effects, involving paraneoplastic mechanisms. Pain secondary to cancer therapy varies with the treatment modalities used: Chemo-radiotherapy protocols are typically associated with painful mucositis and neurotoxicity. Surgical therapies often result in nerve and tissue damage, leading, in the long term, to myofascial and neuropathic pain syndromes. In the present article, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. As a presenting symptom of orofacial cancer, pain is often of low intensity and diagnostically unreliable. Diagnosis, treatment, and prevention of pain in cancer require knowledge of the presenting characteristics, factors, and mechanisms involved.
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PMID:Orofacial pain in cancer: part II--clinical perspectives and management. 1752 49

Cancer-related neuropathic pain derives from peripheral or central lesions of the nervous system and is often associated with the hallmark symptoms of allodynia (pain from a stimulus that does not normally evoke pain) and hyperalgesia (an exaggerated pain response to a normally painful stimulus). Pain is prevalent in patients with cancer and considerably undermines their quality of life, thereby making the development of a comprehensive pain management approach essential. Coanalgesics have been well integrated into cancer pain management strategies and are often used as first-line options for treatment of certain disease processes such as neuropathic pain. These medicines, including antidepressant and anticonvulsant agents, are recommended by evidence-based guidelines, whereas others, such as lidocaine patch 5%, are supported by randomized, controlled, clinical trial data. In addition to understanding which agents are recommended for neuropathic pain, it is useful to know which agents are of limited utility or are to be avoided when prescribing treatment for neuropathic pain. Notwithstanding the need for head-to-head studies before firm statements on comparative efficacy can be made, it is worth considering the numbers needed to treat statistic for the treatment of neuropathic pain with coanalgesics. Potentially harmful treatments are considered, as well as the numbers needed to treat, mechanisms of action, and clinical trial data for agents that can be beneficial for the management of cancer-associated neuropathic pain.
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PMID:Adjuvant agents in cancer pain. 1841 24

Pain and other symptoms of advanced cancer are not treated effectively yet. This review of the literature discusses the needs and latest research findings about pain symptom assessment and management in palliative care. Pain assessment scores should not be followed blindly by a rigid therapeutic regimen. Instead, the health care provider should carefully consider the wide spectrum of possible underlying pain mechanisms. Unidimensional pain rating scales will not detect the impact of affective dimensions on pain expression as accurately as multidimensional rating scales that include various symptoms. Besides assessment tools like numeric rating scales or visual analogue scales, tools now frequently used in the daily clinical setting include the Edmonton Symptom Assessment System, the Mini Mental State Examination, and the CAGE questionnaire (Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers). Recent developments and findings in cancer pain management are illustrated by (1) the use of opioids like morphine, oxycodone, fentanyl, and especially methadone (which has been used increasingly as a secondline drug for opioid-resistant and neuropathic pain, and also for its low cost, long-acting nature, and low side-effect probability, especially in patients with renal failure resulting from the lack of active metabolites); (2) the use of adjuvant therapeutic agents like gabapentin, donepezil, dextromethorphan, and thalidomide; (3) the impact of the immune system on pain, with a concept of targeting immune cells that contain opioids to potentially enhance opioid production, the migration of these cells to tissue lesions, and the release of opioids at the peripheral site to achieve increased peripheral analgesia; and (4) approaches to pain imaging as well as the newly introduced interventions of vertebroplasty and kyphoplasty.
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PMID:Recent developments in cancer pain assessment and management. 1862 86

Bone-cancer-related pain is one of the most disabling factors in patients suffering from primary bone cancer or bone metastases. Recent studies point toward an important role of proinflammatory cytokines, example tumor necrosis factor-alpha (TNF), for tumor growth and bone-cancer-associated pain. Mechanisms by which TNF, through its receptor subtypes, TNF receptor 1 (TNFR1) and -2 (TNFR2), elicits altered sensation and pain behavior, are still incompletely understood. To look for a potential role of TNF in bone cancer pain, cancer-related pain was analyzed in fibrosarcoma-bearing C57Bl/6J wild type mice after systemic antagonism of TNF. To further clarify the role of TNF receptor (TNFR) in bone-cancer pain, naive and fibrosarcoma-bearing C57Bl/ 6J wild type and transgenic mice with a deficiency of TNFR1 (TNFR1ko), TNFR2 (TNFR2ko), and TNFR1+2 (TNFR1+2ko) were compared regarding cancer-related pain and hyperalgesia, tumor growth, osteoclast activation, and spinal astrogliosis. Systemic antagonism of TNF significantly alleviated tactile hypersensitivity and spontaneous bone-cancer-related pain behavior. Most interestingly, combined deletion of the TNFR1 and TNFR2, but not of either gene alone, almost completely inhibited the development of tactile hypersensitivity, whereas spontaneous pain behavior was transiently increased. Accordingly, spinal astrogliosis was markedly reduced, whereas tumor growth was significantly increased in TNFR1+2ko mice. In contrast, deletion of the TNFR1 or TNFR2 gene alone did not change tumor growth or spinal astrogliosis. Our findings suggest that the combined absence of TNFR1 and TNFR2 is necessary for the attenuation of cancer-related tactile hypersensitivity and concomitant spinal astrogliosis, whereas tumor growth seems to be inhibited by combined TNFR activation. These findings support the hypothesis of cytokine-dependent pain development in cancer pain. Differential targeting of TNFR activation could be an interesting strategy in bone-cancer-related pain conditions.
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PMID:Evoked pain behavior and spinal glia activation is dependent on tumor necrosis factor receptor 1 and 2 in a mouse model of bone cancer pain. 2041 92

Neuropathic pain--pain resulting from a lesion, damage, or dysfunction of the somatosensory nervous system--can arise through several distinct etiologies ranging from toxicity, surgery, radiation, and trauma to congenital disorders. Neuropathic pain is widely recognized as a common consequence of cancer and results from administration of several common oncology drugs. It not only impacts quality of life, but it also impacts patient outcomes because of resulting treatment delays, dose reductions, and discontinuations. We estimate that the cost of the problem in the U.S. alone is approximately $2.3 billion. Despite its widely recognized importance, there is a paucity of reliable information available regarding the incidence, prevalence of patient-and physician-reported severity, and time course of cancer-related neuropathic pain. To address this severe knowledge gap, we need new, high-quality, population-based studies of individual cancer pain syndromes and conditions. However, in order to gather this information, we also need substantial improvements in the specific classification of cancer-related neuropathic syndromes and better validated diagnostic tools that can help to elucidate the incidence, prevalence, severity, and potential economic impact of cancer-associated neuropathies.
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PMID:Types and epidemiology of cancer-related neuropathic pain: the intersection of cancer pain and neuropathic pain. 2048 90

Oncologists often manage cancer-associated symptoms including pain. When symptoms are severe, anesthesia-pain medicine (APM) and/or palliative medicine (PM) can effectively treat symptoms. Nevertheless, symptom management may be suboptimal, leading to diminished quality of life (QOL). We assessed the value of PM vs. APM consultation in cancer patients referred for pain management alone. Patients referred to an APM-based Cancer Pain Clinic (CPC) over an 8-month period were evaluated by PM or APM based on the first available appointment. Symptoms and QOL were assessed by the MD Anderson Symptom Inventory and Linear Analog Self-Assessment at baseline and 4-6 weeks after initial encounter. Data were analyzed on an available-case basis. Sixty-two patients (37 PM, 25 APM) completed the initial survey, with 48 patients (31 PM, 17 APM) completing followup. Mean pain score improved from 7.97 to 5.47 in the PM group (P < 0.0001) and from 7.1 to 4.5 (P = 0.29) in the APM group. The PM group demonstrated a clinically significant improvement in 8/19 symptoms vs. 3/19 in the APM group and in 3/5 QOL parameters in the PM group vs. 1/5 in the APM group. Our small sample size weakens our power and ability to detect significant differences between the groups. Only one follow-up symptom-assessment point was obtained. PM consultation is as effective as APM in improving cancer pain but may be more effective with symptom management and improving QOL.
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PMID:An exploratory pilot study of palliative medicine compared to anesthesia-pain consultation for pain in patients with cancer. 2170 3

Amongst cancers with poor prognosis those originating from breast commonly metastasise to the skeleton for the high affinity of breast cancer cells to bone. A(3) adenosine receptor (A(3)AR) agonists were found to be potent anti-tumour agents even if their effect on bone-residing breast cancer has not yet been investigated. An animal model of surgery-induced metastasis was used to mimic the human condition in an attempt to develop a novel effective treatment strategy. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells developed cancer-associated osteolytic lesions and structural damage that were monitored by microcomputed tomography imaging and histological analysis. To address the involvement of A(3)ARs in tumour-related signalling pathway, A(3)AR expression and functional role were analysed in MRMT-1 cells. The effect of chronic treatment with an A(3)AR agonist, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-uronamide (Cl-IB-MECA) in comparison with cisplatin, was evaluated on rat tumour growth and bone cancer pain. A(3)ARs were expressed in MRMT-1 cells and their activation reduced NF-kB, increased p53 expression and apoptosis, inhibited tumour cell proliferation and migration. In vivo Cl-IB-MECA administration, started on day 1 after tumour cell injection, produced a significant reduction in tumour growth and cancer pain. Cl-IB-MECA treatment, performed on days 5 and 10 after the tumour cell inoculation, revealed the capability of A(3)AR stimulation to partially reduce tumour progression. Our findings highlighted the effectiveness of A(3)AR stimulation in the inhibition of breast tumour-derived bone metastasis growth strongly suggesting that targeting A(3)ARs may have promising therapeutic value in the treatment of bone-residing breast cancer.
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PMID:The stimulation of A(3) adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. 2277 Aug 90


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