Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain in patients with metastatic cancer contributes to increased suffering in those already burdened by their advancing illness. The causes of this pain are unknown, but are likely to involve the action of tumour-associated mediators and their receptors. In recent years, several chemical mediators have increasingly come to the forefront in the pathophysiology of cancer pain. One such mediator, endothelin-1 (ET-1), is a peptide of 21 amino acids that was initially shown to be a potent vasoconstrictor. Extensive research has revealed that members of the ET family are indeed produced by several epithelial cancerous tumours, in which they act as autocrine and/or paracrine growth factors. Several preclinical and clinical studies of various malignancies have suggested that the ET axis may represent an interesting contributor to tumour progression. In addition, evidence is accumulating to suggest that ET-1 may contribute to pain states both in humans and in other animals. ET-1 both stimulates nociceptors and sensitises them to painful stimuli. Selective stimulation of ET receptors has been implicated as a cause of inflammatory, neuropathic and tumoural pain. ET-1-induced pain-related behaviour seems to be mediated either solely by one receptor type or via both endothelin-A receptors (ETAR) and endothelin-B receptors (ETBR). Whereas stimulation of ETAR on nociceptors always elicits a pain response, stimulation of ETBR may cause analgesia or elicit a pain response, depending on the conditions. The administration of ETAR antagonists in the receptive fields of these nociceptors has been shown to ameliorate pain-related behaviours in animals, as well as in some patients with advanced metastatic prostate cancer. The identification of tumour-associated mediators that might directly or indirectly cause pain in patients with metastatic disease, such as ET-1, should lead to improved, targeted analgesia for patients with advanced cancer. In this review, we will describe the current status of the role of ET-1 in different types of painful syndromes, with special emphasis on its role in the pathophysiology of cancer pain. Finally, potential new treatment options that are based on the role of the ET axis in the pathophysiology of cancer are elaborated.
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PMID:Endothelin-1-induced pain and hyperalgesia: a review of pathophysiology, clinical manifestations and future therapeutic options. 1819 15

Cancer pain impairs the quality of life of cancer patients, but opioid intervention can cause significant side effects that further decrease quality of life. Although electroacupuncture (EA) has been used to treat cancer pain, its mechanisms are largely unknown. To examine its effects and underlying mechanisms on cancer pain, we injected AT-3.1 prostate cancer cells into the tibia to induce bone cancer in the male Copenhagen rat. The resulting pain was treated with 10Hz/2mA/0.4ms pulse EA for 30min daily at the point equivalent to the human acupoint GB30 (Huantiao) between days 14 and 18 after the injection. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in paw withdrawal latency (PWL) to a noxious thermal stimulus, and mechanical hyperalgesia, a decrease in paw withdrawal pressure threshold (PWPT), was measured at baseline and 20min after the EA treatment. Preprodynorphin mRNA and dynorphin were determined by RT-PCR and immunohistochemistry, respectively. Thermal and mechanical hyperalgesia developed ipsilaterally between days 12 and 18 after cancer cell inoculation. EA significantly (P<0.05) attenuated this hyperalgesia, as shown by increased PWL and PWPT, and inhibited up-regulation of preprodynorphin mRNA and dynorphin compared to sham control. Intrathecal injection of antiserum against dynorphin A (1-17) also significantly inhibited the cancer-induced hyperalgesia. These results suggest that EA alleviates bone cancer pain at least in part by suppressing dynorphin expression, and they support the clinical use of EA in the treatment of cancer pain.
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PMID:Electroacupuncture attenuates bone-cancer-induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model. 1822

It has been shown that interleukin-1beta (IL-1beta) facilitates nociception during neuropathic and inflammatory pain, but its involvement in bone cancer pain and its mechanisms have not previously been established. This study is an investigation of IL-1beta spinal expression and the N-methyl-D-aspartate (NMDA) receptor (NMDAR) NR1 subunit phosphorylation during cancer pain, co-localization of IL-1 receptor type I (IL-1RI) and NMDAR in the spinal cord, and the effects of IL-1 receptor antagonist (IL-1ra) on NMDAR1 (NR1) phosphorylation and hyperalgesia in a rat model of bone cancer pain. Cancer was induced by injecting AT-3.1 prostate cancer cells into the tibia of the male Copenhagen rat. Phosphorylation of NR1, an essential subunit of the NMDAR, is known to modulate NMDAR activity and facilitate pain. Mechanical hyperalgesia, established by a decrease in paw withdrawal pressure threshold (PWPT), was measured at baseline and 2 h after IL-1ra treatment. IL-1ra was given (i.t.) daily for 7 days between days 13 and 19 after the cancer cell inoculation. Spinal cords were removed for Western blot to measure IL-1beta and NR1 phosphorylation and for double immunostaining of IL-1RI and NR1. The data showed that 1) spinal IL-1beta was up-regulated and NR1 phosphorylation was increased, 2) IL-1ra at 0.1 mg/rat significantly (P<0.05) inhibited mechanical hyperalgesia, increasing PWPT on day 14 from 71.1+/-3.1-85.3+/-4.6 g and on day 19 from 73.5.0+/-3.5-87.1+/-3.7 g, and inhibited NR1 phosphorylation compared with saline control, and 3) IL-1RI is localized in NR1-immunoreactive neurons within the spinal cord. The results suggest that spinal IL-1beta enhances NR1 phosphorylation to facilitate bone cancer pain.
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PMID:Interleukin 1beta facilitates bone cancer pain in rats by enhancing NMDA receptor NR-1 subunit phosphorylation. 1855 6

Pain is a significant symptom in cancer patients. Understanding of patients' experiences in relation to pain management is important in evidence-based nursing in the field of pain. The aim of this study was to explore cancer patients' experiences of nursing pain management during hospitalization for cancer treatment. Eighteen cancer patients participated in the study, all with advanced cancer, including skeleton metastases. The female participants all had breast cancer, and the male participants all had prostate cancer. Data were collected by in-depth interviews, and qualitative description was used to entail low-inference interpretation to reach an understanding of the essence of pain and nursing pain management. Patients found it somewhat difficult to express their expectations of nursing pain management and competencies. However, 1) being present and supportive; 2) giving information and sharing knowledge; 3) taking care of medication; and 4) recognizing the pain emerged as themes in nursing pain management. Although patients believed that nurses were caring persons, they perceived differences between nurses in the ways they handled pain management. Furthermore, some patients experienced a lack of information from nurses in relation to pain management. Although cancer patients' experiences showed the importance of nurses in pain management, it seems that nurses should have a clearer role in cancer pain management in relation to counseling and patient education. The results from this study can increase nurses' awareness of their role in pain management as a first step in improving pain management for patients.
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PMID:Nursing pain management--a qualitative interview study of patients with pain, hospitalized for cancer treatment. 1926 83

Metastatic bone disease (MBD) is the most common cause of cancer pain and of serious skeletal-related events (SREs) reducing quality of life. Management of MBD involves a multimodal approach aimed at delaying the first SRE and reducing subsequent SREs. The objective of the study was to characterise the hospital burden of disease associated with MBD and SREs following breast, lung and prostate cancer in Spain. Patients admitted into a participating hospital, between 1 January 2003 and 31 December 2003, with one of the required cancers were identified and selected for inclusion into the study. The index admission to hospital, incidence of patients admitted and hospital length of stay were analysed. There were 28,162 patients identified with breast, lung and prostate cancer. The 3 year incidence rates of hospital admission due to MBD were 95 per 1000 for breast cancer, 156 per 1000 for lung cancer and 163 per 1000 for prostate cancer. For patients admitted following an SRE, the incidence rates were 211 per 1000 for breast cancer, 260 per 1000 for lung cancer and 150 per 1000 for prostate cancer. This study has shown that cancer patients consume progressively more hospital resources as MBD and subsequent SREs develop.
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PMID:The hospital burden of disease associated with bone metastases and skeletal-related events in patients with breast cancer, lung cancer, or prostate cancer in Spain. 1970 28

Pain frequently accompanies cancer. What remains unclear is why this pain frequently becomes more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the tumor-bearing tissue undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain chronic pain. Injection of canine prostate cancer cells into mouse bone induces a remarkable sprouting of calcitonin gene-related peptide (CGRP(+)) and neurofilament 200 kDa (NF200(+)) sensory nerve fibers. Nearly all sensory nerve fibers that undergo sprouting also coexpress tropomyosin receptor kinase A (TrkA(+)). This ectopic sprouting occurs in sensory nerve fibers that are in close proximity to colonies of prostate cancer cells, tumor-associated stromal cells and newly formed woven bone, which together form sclerotic lesions that closely mirror the osteoblastic bone lesions induced by metastatic prostate tumors in humans. Preventive treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. Interestingly, reverse transcription PCR analysis indicated that the prostate cancer cells themselves do not express detectable levels of mRNA coding for NGF. This suggests that the tumor-associated stromal cells express and release NGF, which drives the pathological reorganization of nearby TrkA(+) sensory nerve fibers. Therapies that prevent this reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive cancer pain and lead to more effective control of this chronic pain state.
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PMID:Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. 2104 22

Early, preemptive blockade of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) attenuates tumor-induced nerve sprouting and bone cancer pain. A critical unanswered question is whether late blockade of NGF/TrkA can attenuate cancer pain once NGF-induced nerve sprouting and neuroma formation has occurred. By means of a mouse model of prostate cancer-induced bone pain, anti-NGF was either administered preemptively at day 14 after tumor injection when nerve sprouting had yet to occur, or late at day 35, when extensive nerve sprouting had occurred. Animals were humanely killed at day 70 when, in vehicle-treated animals, significant nerve sprouting and neuroma formation was present in the tumor-bearing bone. Although preemptive and sustained administration (days 14-70) of anti-NGF more rapidly attenuated bone cancer nociceptive behaviors than late and sustained administration (days 35-70), by day 70 after tumor injection, both preemptive and late administration of anti-NGF significantly reduced nociceptive behaviors, sensory and sympathetic nerve sprouting, and neuroma formation. In this model, as in most cancers, the individual cancer cell colonies have a limited half-life because they are constantly proliferating, metastasizing, and undergoing necrosis as the parent cancer cell colony outgrows its blood supply. Similarly, the sensory and sympathetic nerve fibers that innervate the tumor undergo sprouting at the viable/leading edge of the parent tumor, degenerate as the parent cancer cell colony becomes necrotic, and resprout in the viable, newly formed daughter cell colonies. These results suggest that preemptive or late-stage blockade of NGF/TrkA can attenuate nerve sprouting and cancer pain.
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PMID:Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain. 2186 66

Nerve growth factor (NGF) and its precursor (proNGF) are primarily considered as regulators of neuronal function that induce their responses via the tyrosine kinase receptor TrkA and the pan-neurotrophin receptor p75NTR. It has been generally held that NGF exerts its effects primarily through TrkA, inducing a cascade of tyrosine kinase-initiated responses, while proNGF binds more strongly to p75NTR. When this latter entity interacts with a third receptor, sortilin, apoptotic responses are induced in contrast to the survival/differentiation associated with the other two. Recent studies have outlined portions of the downstream phosphoproteome of TrkA in the neuronal PC12 cells and have clarified the contribution of individual docking sites in the TrkA endodomain. The patterns observed showed a similarity with the profile induced by the epidermal growth factor receptor, which is extensively associated with oncogenesis. Indeed, as with other neurotrophic factors, the distribution of TrkA and p75NTR is not limited to neuronal tissue, thus providing an array of targets outside the nervous systems. One such source is breast cancer cells, in which NGF and proNGF stimulate breast cancer cell survival/growth and enhance cell invasion, respectively. This latter activity is exerted via TrkA (as opposed to p75NTR) in conjunction with sortilin. Another tissue overexpressing proNGF is prostate cancer and here the ability of cancer cells to induce neuritogenesis has been implicated in cancer progression. These studies show that the non-neuronal functions of proNGF/NGF are likely integrated with their neuronal activities and point to the clinical utility of these growth factors and their receptors as biomarkers and therapeutic targets for metastasis and cancer pain.
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PMID:NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling. 2549 71

Cancer-induced bone pain is abundant among advanced-stage cancer patients and arises from a primary tumor in the bone or skeletal metastasis of common cancer types such as breast, lung, or prostate cancer. Recently, antibodies targeting nerve growth factor (NGF) have been shown to effectively relieve neuropathic and inflammatory pain states in mice and in humans. Although efficacy has been shown in mice on a behavioral level, effectiveness in preventing pain-induced functional rearrangements in the central nervous system has not been shown. Therefore, we assessed longitudinal whole-brain functional connectivity using resting-state functional magnetic resonance imaging in a mouse model of cancer-induced bone pain. We found functional connectivity between major hubs of ascending and descending pain pathways such as the periaqueductal gray, amygdala, thalamus, and cortical somatosensory regions to be affected by a developing cancer pain state. These changes could be successfully prevented through prospective administration of a monoclonal anti-NGF antibody (mAb911). This indicates efficacy of anti-NGF treatment to prevent pain-induced adaptations in brain functional networks after persistent nociceptive input from cancer-induced bone pain. In addition, it highlights the suitability of resting-state functional magnetic resonance imaging readouts as an indicator of treatment response on the basis of longitudinal functional network changes.
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PMID:Prospective administration of anti-nerve growth factor treatment effectively suppresses functional connectivity alterations after cancer-induced bone pain in mice. 3016 Oct 41

The pain associated with frequent secondary bone involvement can negatively affect the quality of life of patients affected by metastatic prostate cancer. Its proper diagnostic framework is important to optimize the treatment. We describe the case of a patient suffering from breaktrough cancer pain treated with sublingual fentanyl.
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PMID:[Breaktrough cancer pain in metastatic prostate adenocarcinoma: a case report.] 3096 57


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