Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MKT-077, a delocalized lipophilic cation, selectively targets cancer cells. MKT-077 has been reported to inhibit the growth of several tumor types and has undergone phase I clinical testing. We have examined the effect of MKT-077, alone and in combination with the antidiarrheal drug loperamide. Ten human cancer cell lines, four prostate (PC3, DU145, LNCaP, MDA-PCA-2B), two breast (MCF-7 and MDA-MB-231) and four colon (LoVo, Colo320DM, SW1116 and LS174t) were tested in vitro. Cells were grown to confluency prior to treatment. Loperamide potentiated the antiproliferative effect of MKT-077 in all ten cell lines, in a dose-dependent manner. The sensitivity of MDA-PCA-2B cells, the two breast and four colon cancer cell lines to MKT-077 was relatively low (>2.5 microg/ml MKT-077 required to inhibit growth by 95%). In these cell lines, 0.5-5 microg/ml (1-10 microM) loperamide caused a marked increase in the response to MKT-077. Loperamide is known to activate micro-opioid receptors at nanomolar concentrations and block voltage-gated calcium channels at micromolar doses. We found that calcium channel-blockers diltiazem and nifedipine (10-20 microg/ml), as well as tamoxifen (1.5-2.5 microg/ml) can also potentiate the growth-inhibitory effects of MKT-077. These synergistic interactions could be exploited for therapeutic benefit.
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PMID:Potentiation of the antiproliferative activity of MKT-077 by loperamide, diltiazem and tamoxifen. 1453 37

We investigated coexisting autoantibodies in sera of 553 patients with a neurological presentation and one or more paraneoplastic neuronal nuclear or cytoplasmic autoantibodies: antineuronal nuclear autoantibody type 1 (ANNA-1), ANNA-2, ANNA-3; Purkinje cell cytoplasmic autoantibody type 1 (PCA-1), PCA-2; and CRMP-5-immunoglobulin G or amphiphysin-immunoglobulin G. Except for PCA-1, which occurred alone, 31% of sera had more than one of these autoantibodies. In addition, 25% of sera had neuronal calcium channel (P/Q-type or N-type), potassium channel, ganglionic acetylcholine receptor, muscle acetylcholine receptor, or striational antibodies. The autoantibody profiles observed in patients with paraneoplastic disorders imply the targeting of multiple onconeural antigens and predict the patient's neoplasm, but not a specific neurological syndrome.
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PMID:Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. 1550 22

There is experimental evidence that nimodipine, an L-type dihydropiridine calcium channel blocker with relatively high blood-brain barrier penetration, enhances the antinociceptive properties of morphine. We tested the hypothesis that oral nimodipine taken preoperatively and 6 hourly for 48 h postoperatively would reduce visual analog scale pain scores and morphine consumption in morphine-naive patients with acute postoperative pain. Forty patients undergoing total knee replacement surgery (age 70 +/- 7 yr, 28 male) were randomized by computer-generated numbers to receive capsules containing either nimodipine 30 mg or placebo in a double-blind study design. All patients received 3 capsules (nimodipine 90 mg or placebo) 1-2 h before induction of anesthesia followed by oral nimodipine 30 mg or placebo 6 hourly for 48 hours postoperatively. Spinal anesthesia was induced with hyperbaric bupivacaine 0.5% (2.4-3.0 mL) and fluids and ephedrine were given at the discretion of the anesthesiologist. Morphine patient-controlled analgesia (PCA, bolus 1 mg, lockout 5 min) was given for postoperative analgesia. Primary outcome measures were visual analog pain scores at rest and on moving (sitting forward) and PCA morphine consumption. Morphine consumption was significantly larger in nimodipine patients at 12 h (39 +/- 18 versus 29 +/- 15; P = 0.04), 24 h (62 +/- 23 versus 45 +/- 24; P = 0.02), and 48 h (88 +/- 34 versus 61 +/- 27; P = 0.01). There were no significant differences in pain scores at rest or moving or in time to first use of morphine analgesia. This study has demonstrated increased morphine consumption after 12 h in postoperative patients receiving nimodipine, suggesting that, in patients undergoing knee replacement surgery, it has no adjunctive analgesic effect and may actually inhibit the analgesic effect of morphine.
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PMID:Perioperative nimodipine and postoperative analgesia. 1642 51