Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The therapeutic opioid methadone, used to treat cancer pain and opioid addiction, is also a potent inducer of apoptosis in human lung cancer cells, thereby inhibiting their growth. However, in contrast to its central nervous system (CNS) actions, this effect appears to be mediated through a non-opioid mechanism involving bombesin, an autocrine growth-stimulatory factor that plays a central role in the early events of pulmonary carcinogenesis. Exposure of 'variant' small cell lung carcinoma (SCLC) and non-SCLC cells, which secrete low concentrations (< 0.01 pmol/mg protein) of bombesin, to nanomolar concentrations of methadone resulted in increased levels of mitogen-activated protein (MAP) kinase phosphatases and inactivation of MAP kinase, suppression of the bcl-2 protein, and induction of apoptosis. These effects of methadone were reversed by the addition of bombesin to the culture medium, at concentrations of < 1 microM, and 'classic' SCLC cells, which secrete high concentrations of bioactive bombesin (> 6 pmol/mg protein), were found not to respond to methadone. Thus, methadone's effectiveness is dependent upon the concentration of bioactive bombesin secreted by lung cancer cells. Methadone treatment suggests a novel therapeutic approach for patients presenting 'variant' SCLC and non-SCLC morphologies, since they respond less to conventional therapy.
 ...
PMID:Effects of bombesin on methadone-induced apoptosis of human lung cancer cells. 1035 47

Three potential applications of NO-donating NSAIDs in human cancer include their use: as chemopreventive agents; against already developed cancers (chemotherapy); and for the control of cancer symptoms, notably cancer pain. The evidence to date of greater safety and enhanced efficacy of NO-donating NSAIDs underscores their potential to prevent colon cancer and overcome the limitations of traditional NSAIDs. NO-donating NSAIDs affect several pathways critical to colon carcinogenesis and this may explain in part their greater efficacy in colon cancer prevention as assessed in preclinical models.
 ...
PMID:NO-NSAIDs and cancer: promising novel agents. 1284 41

Approximately 30 years ago, we developed 2 mouse lines with enhanced and decreased opioid system activity using bidirectional selection for high (high analgesia [HA] line) and low (low analgesia [LA] line) swim stress-induced analgesia. These mouse lines differ substantially in pain sensitivity, measured as hind paw withdrawal latency in a hot plate test. Moreover, compared with the LA mice, the HA mice exhibited reduced energy expenditure under stress and different depression-like behavior as well as higher sensitivity to mutagens and the high frequency of spontaneous and carcinogen-induced tumors. In the current study, we observed distinct differences in the growth rate of orthotopically implanted melanoma and the onset of cancer pain. Whereas the HA line was prone to tumors and carcinogenesis was rapid in all specimens, the LA mice either did not develop tumors (70%) or developed tumors that often regressed spontaneously (30%). Animals from both lines developed robust thermal hypersensitivity in the tumor-bearing paw compared with animals that were injected with saline. However, we found that hyperalgesia in tumor-bearing mice persists for a much shorter time in the HA than in LA mice. Naltrexone, given subcutaneously, restored hyperalgesia in the HA mice, whereas it was ineffective in the LA mice. The results suggest that activity of the opioid system may influence carcinogenesis and the intensity of cancer pain and indicates that HA and LA mice are good models for such studies.
 ...
PMID:Distinct susceptibility to inoculated melanoma and sensitivity to cancer pain in mouse lines with high and low sensitivity to stress. 2321 41

Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.
 ...
PMID:Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements. 2484 Nov 74

Oral cancers are often severely painful and clinically difficult to manage. Few researchers have investigated the neurobiologic factors responsible for cancer pain; however, the study of oral cancer pain might inform us about the fundamental biology of cancer. The purpose of the present report was to summarize the clinical challenges inherent in oral cancer pain management, oral cancer pain mechanisms and mediators, and the convergence of the investigation of carcinogenesis and pain.
...
PMID:The Neurobiology of Cancer Pain. 2660 42