Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated.
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PMID:Analgesic drugs in the management of pain. 1 28

Many tumors, especially when metastasizing, produce a variety of symptoms. Two frequent sets of complications due to metastasizing cancer (mainly to the bones), i.e. vertebral metastases and chronic pain, are reviewed. In the case of vertebral metastases, the fitting of an orthopedic corset should--and as a rule can--be avoided. Treatment of this complication is by systemic therapy and/or radiotherapy. Symptoms or signs of medullary compression are indications for emergency treatment by the radiotherapist or the neurosurgeon. In the case of chronic pain, regular oral intake of the Brompton mixture is an alternative to injections of analgesics in that it prevents rather than alleviates pain and is only slightly addiction-forming.
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PMID:[Therapy of complications due to neoplasm metastases]. 68 96

A series of 252 patients with terminal cancer (mostly with bony metastases) were treated with epidural morphine. Results were good to excellent pain relief in 85% of patients, but those with malignant growths above the neck showed relatively poor response. For those who survived more than 3 months, the daily morphine requirement increased progressively from 3.5 +/- 0.6 mg to 19.5 +/- 5.3 mg. Drug tolerance developed but no signs of addiction were noted. Respiratory depression was detected in 2 cases due to negligence but resolved uneventfully. No infection of the central nervous system was seen. Systemic reactions were mild and transient. The major drawbacks were catheter failure which required reinsertion, and sharp pain during injection in the later stages of therapy. Despite the side-effects, percutaneous epidural morphine is a useful treatment modality of pain control in cancer patients because it is readily available, safe and not too expensive.
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PMID:A preliminary study of long-term epidural morphine for cancer pain via a subcutaneously implanted reservoir. 272 85

The purposes of this study were to (a) test the feasibility of the Cancer Total Quality Pain Management (TQPM) Patient Assessment Tool in a population of oncology inpatient and outpatients; and (b) identify factors associated with poor pain relief. The Cancer TQPM Tool was adapted from the American Pain Society's Quality Assurance Standards on Acute Pain and Cancer Pain and was tested in a convenience sample of 200 patients. The majority of patients reported that the TQPM Tool was easy to understand and to use, providing evidence for the feasibility of the tool. Factors associated with higher pain intensity included the inpatient setting, the presence of metastatic disease, hesitancy in bothering the nurse, and concerns regarding tolerance and addiction. Although there was a strong relationship between concern about addiction and concern about tolerance, fear of tolerance appeared to have a greater effect on pain intensity scores than did fear of addiction. The findings from this study suggest that the Cancer TQPM Patient Assessment Tool can be used effectively in both inpatients and outpatients to determine outcomes and the quality of cancer pain management, as well identify factors associated with poor pain control. Clinical implications include more effective education of patients and caregivers, including equivalent emphasis on tolerance and addiction.
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PMID:Barriers to cancer pain relief: fear of tolerance and addiction. 970 52

It is estimated that 40% to 50% of patients with metastatic disease and 90% of patients with terminal cancer experience unrelieved pain. Furthermore, inadequate treatment of cancer pain is a greater possibility if the patient is a substance abuser. In this paper, we will explore pertinent conceptual and clinical aspects of addiction that can assist in improving the identification and treatment of patients with substance use disorders.
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PMID:Substance abuse issues in cancer pain. 1200 88

Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer. Here, by integrating SNP array-based genetic maps with gene expression signatures derived from NCI60 cell lines, we identified the melanocyte master regulator MITF (microphthalmia-associated transcription factor) as the target of a novel melanoma amplification. We found that MITF amplification was more prevalent in metastatic disease and correlated with decreased overall patient survival. BRAF mutation and p16 inactivation accompanied MITF amplification in melanoma cell lines. Ectopic MITF expression in conjunction with the BRAF(V600E) mutant transformed primary human melanocytes, and thus MITF can function as a melanoma oncogene. Reduction of MITF activity sensitizes melanoma cells to chemotherapeutic agents. Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm. Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression.
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PMID:Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. 1600 Oct 50

Malignant progression and tumor metastasis is a complex process enabled by the intrinsic genomic instability of the tumor cells and supported by a plethora of recruited cell types within the tumor microenvironment. Propelled by a selective pressure to overcome tissue homeostatic mechanisms, a metastatic "super-cell" emerges whose phenotype is associated with the cellular capacity for uncontrolled growth, resistance to apoptosis, high invasive potential, and effective neoangiogenesis. While genetic alterations arise early in the course of melanoma development, the progression toward metastatic disease is accompanied by deregulated expression of a number of transcription factors. In melanoma, acquisition of the metastatic phenotype involves the loss of Activator Protein-2alpha (AP-2alpha) and gain in expression of cAMP-responsive element (CRE)-binding protein/Activating Transcription Factor-1 (CREB/ATF-1) family transcription factors. Together with the upregulation of ATF-2, SNAIL/SLUG, Nuclear Factor kappaB, STAT3 and 5, and other transcription factors, these changes result in the aberrant expression of cellular adhesion molecules, matrix-degrading enzymes as well as other factors that enable a complex interaction of metastatic cells with the extracellular milieu. Similar to the case of oncogene addiction, the tumorigenicity and metastatic potential of melanoma can be greatly inhibited by altering the activity of the above-named transcription factors, therefore indicating new treatment prospects.
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PMID:Transcriptional control of the melanoma malignant phenotype. 1869 65

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms that require a multidisciplinary approach for an optimal management. The lack of effectiveness of traditional DNA-damaging agents has led to the exploration of new targeted drugs in order to exploit phenotypical features of GEP-NET therapy. However, due to the orphan setting of these tumors, deeper characterization of molecular features and pathways that characterize cell growth, apoptosis, angiogenesis, and invasion are lacking, particularly genetic mutations or epigenetic alterations that generate oncogenic dependency or even addiction. The PI3K-AKT-mTOR pathway has been implicated as having a crucial role in GEP-NETs not only due to the overexpression of several growth factors and their receptors that finally activate this axis but also hereditary syndromes with constitutive activation of the mTOR pathway with high incidence of GEP-NETs. In this article, we aim to review the recent development of the main molecules that target mTOR complex and have showed promising activity in the treatment of GEPNETs.
Cancer Metastasis Rev 2011 Mar
PMID:Innovations therapy: mammalian target of rapamycin (mTOR) inhibitors for the treatment of neuroendocrine tumors. 2131 55

Advanced non-small lung cancer (NSCLC) remains almost uniformly lethal with marginal long-term survival despite efforts to target specific oncogenic addiction pathways that may drive these tumors with small molecularly targeted agents and biologics. The EML4-ALK fusion gene encodes a chimeric tyrosine kinase that activates the Ras signaling pathway, and this fusion protein is found in approximately 5% of NSCLC. Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments. We present the clinicopathologic features of three patients with metastatic NSCLC harboring the EML4-ALK translocation that developed isolated central nervous system (CNS) metastases in the presence of good disease control elsewhere in the body. These cases suggest a differential response of NSCLC to Crizotinib in the brain in comparison to other sites of disease, and are consistent with a previous report of poor CNS penetration of Crizotinib. Results of ongoing clinical trials will clarify whether the CNS is a major sanctuary site for EML4-ALK positive NSCLC being treated with Crizotinib. While understanding molecular mechanisms of resistance is critical to overcome therapeutic resistance, understanding physiologic mechanisms of resistance through analyzing anatomic patterns of failure may be equally crucial to improve long-term survival for patients with EML4-ALK translocation positive NSCLC.
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PMID:Isolated central nervous system progression on Crizotinib: an Achilles heel of non-small cell lung cancer with EML4-ALK translocation? 2298 31

Metastasis-associated phosphatase of regenerating liver-3 (PRL-3) has pleiotropic effects in driving cancer progression, yet the signaling mechanisms of PRL-3 are still not fully understood. Here, we provide evidence for PRL-3-induced hyperactivation of EGFR and its downstream signaling cascades in multiple human cancer cell lines. Mechanistically, PRL-3-induced activation of EGFR was attributed primarily to transcriptional downregulation of protein tyrosine phosphatase 1B (PTP1B), an inhibitory phosphatase for EGFR. Functionally, PRL-3-induced hyperactivation of EGFR correlated with increased cell growth, promigratory characteristics, and tumorigenicity. Moreover, PRL-3 induced cellular addiction to EGFR signaling, as evidenced by the pronounced reversion of these oncogenic attributes upon EGFR-specific inhibition. Of clinical significance, we verified elevated PRL-3 expression as a predictive marker for favorable therapeutic response in a heterogeneous colorectal cancer (CRC) patient cohort treated with the clinically approved anti-EGFR antibody cetuximab. The identification of PRL-3-driven EGFR hyperactivation and consequential addiction to EGFR signaling opens new avenues for inhibiting PRL-3-driven cancer progression. We propose that elevated PRL-3 expression is an important clinical predictive biomarker for favorable anti-EGFR cancer therapy.
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PMID:Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells. 2386 4


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