naloxone and Colonic-Neoplasms

Severe pruritus is a frequent complication of cholestasis. Both serotonin and opioids play an important role in the development of this symptom. Guidelines to provide rational management of pruritus of cholestasis do not exist. We describe a patient with complex and malignant course of pruritus. She responded to several measures proposed (among other naltrexone), but rapidly became tolerant to them. Buprenorphine with an ultra low dose of naloxone was able to control her symptoms without development of tolerance until her death.

Topics: Aged; Buprenorphine; Cholestasis; Colonic Neoplasms; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Liver Neoplasms; Naloxone; Narcotic Antagonists; Pruritus

Opioid growth factor (OGF) is a native endogenous opioid peptide ([Met5]-enkephalin) that interacts with the OGF receptor (OGFr), and serves as a tonically active negative growth factor in neoplasia. To inquire whether OGF modulates anchorage-independent growth, HT-29 human colon cancer cells were grown in soft agar and subjected to this peptide. In contrast to controls, HT-29 cells exposed to OGF had 57% fewer colonies, and these colonies were reduced in area by 75%. The changes induced by OGF were abolished by concomitant treatment with naloxone, indicating a receptor-mediated mechanism for peptide activity. Continuous blockade of opioid-receptor interactions with the potent and long-acting opioid antagonist, naltrexone (NTX), revealed an increase of 81 and 49% in the number and area, respectively, of colonies compared to control levels. These data suggest that OGF is tonically active in neoplastic cells growing in soft agar medium. HT-29 cells studied under anchorage-independent conditions were not influenced in growth by a variety of natural and synthetic opioids, including those selective for micro, delta, and kappa opioid receptors. Similar effects on anchorage-independent growth by OGF and NTX observed for HT-29 cells were recorded in pancreatic adenocarcinoma cells (Mia PaCa-2, Panc-1) and squamous cell carcinoma of the head and neck (CAL-27). These results using anchorage-independent conditions are consistent with previous data showing that OGF can markedly influence tumor growth in xenografts, and suggest that clonogenic assays can be utilized as indicators of tumorigenicity when tumor transplantation experiments are restricted.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Adhesion; Cell Division; Colonic Neoplasms; Colony-Forming Units Assay; Enkephalin, Methionine; Head and Neck Neoplasms; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Pancreatic Neoplasms; Receptors, Opioid; Transplantation, Heterologous; Tumor Cells, Cultured

The effect of the opioid receptor agonist methionine enkephalin (Met-enkephalin) and the opioid receptor antagonist naloxone on colonic carcinogenesis induced by azoxymethane was investigated in Wistar rats. Rats received ten weekly injections of 7.4 mg/kg of body weight of azoxymethane and injections of Met-enkephalin (50 micrograms/kg of body weight), naloxone (2 mg/kg of body weight), or Met-enkephalin (50 micrograms/kg of body weight) plus naloxone (2 mg/kg of body weight) once every 2 days. In wk 40, the group treated with Met-enkephalin had a significantly increased incidence of colonic tumors. A combination of Met-enkephalin and naloxone attenuated the enhancing effect by Met-enkephalin on the development of colonic tumors. Administration of naloxone alone had no influence on colonic tumorigenesis. During and after administration of the carcinogen, the bromodeoxyuridine-labeling indices of the colon mucosa and/or cancers were significantly increased in rats treated with Met-enkephalin. However, a combination of Met-enkephalin and naloxone significantly decreased the labeling indices of the colon mucosa and/or cancers. These findings indicate that Met-enkephalin enhanced colon carcinogenesis and that naloxone attenuated this enhancement. Because naloxone is an opioid receptor antagonist, these findings also indicate that the enhancing effect of Met-enkephalin on colon carcinogenesis may be mediated through opioid receptors.

Topics: Adenocarcinoma; Animals; Azoxymethane; Colon; Colonic Neoplasms; Drug Administration Schedule; Drug Synergism; Enkephalin, Methionine; Male; Naloxone; Rats; Rats, Inbred Strains

Topics: Adenocarcinoma; Colonic Neoplasms; Half-Life; Humans; Infusion Pumps; Injections, Epidural; Male; Middle Aged; Morphine; Naloxone; Palliative Care; Rectal Neoplasms; Respiration