buprenorphine and Breast-Neoplasms

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline (1 ml/kg). Tumours were imaged and welfare was assessed using body weight, behaviour and nociceptive responses. In study 1, BALB/c mice were inoculated with 4T1 mammary carcinoma or saline during surgery or anaesthesia. As pre-treatment with a single buprenorphine dose appeared beneficial to cancer growth consistency, a second cohort of mice additionally received saline or buprenorphine at 12 and 24 h. Surgery resulted in increased mammary tumour growth and lung metastases. These unwanted effects were lessened by buprenorphine pre-treatment, especially when given repeatedly. Mammary tumour-bearing mice became less active and nociceptive thresholds declined over time, indicating some discomfort as tumours grew. In study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to determine whether meloxicam or buprenorphine affected cancer seeding of the lungs. While meloxicam reduced B16 lung seeding, buprenorphine did not. Mechanical thresholds decreased as cancer developed in mice bearing melanoma, but the magnitude of this was insufficient to conclude that there were any significant welfare concerns. This study highlights the scientific value in utilising non-surgical models, where possible. When surgery must be performed at the time of tumour inoculation, the effects of this should be controlled with appropriate analgesics to enhance the value and possibly translation of the research.

Topics: Analgesics; Animal Welfare; Animals; Breast Neoplasms; Buprenorphine; Cell Line, Tumor; Disease Models, Animal; Female; Lung Neoplasms; Mammary Neoplasms, Experimental; Melanoma, Experimental; Meloxicam; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Pain; Thiazines; Thiazoles; Xenograft Model Antitumor Assays

Not all opioids employed in clinical practice share the same immunosuppressive properties. The potent partial micro-agonist buprenorphine appears to exhibit a neutral effect on the immune responses. Surgery stress is associated with decreased natural killer cell activity (NK) and enhancement of tumor metastasis in rats. We analyzed the ability of buprenorphine to prevent the effects of experimental surgery on HPA activation (plasma corticosterone levels), NK activity and lung diffusion of the NK sensitive tumor MADB106. Buprenorphine (0.1mg/kg) was compared with equianalgesic doses of fentanyl (0.1mg/kg) and morphine (10mg/kg) in this animal model. In normal animals morphine and fentanyl stimulate the HPA axis, decrease NK activity and augment tumor metastasis, while buprenorphine is devoid of these effects. Surgery significantly raised corticosterone levels, suppressed NK activity and increased MADB106 metastasis. Only buprenorphine was able to prevent the neuroendocrine and immune system alterations and ameliorate the increase of tumor metastasis induced by surgical stress. These preclinical findings suggest that an adequate treatment of surgically induced stress immunosuppression with an opioid drug devoid of immunosuppressive effects may also play a protective role against the metastatic diffusion following cancer surgery.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Breast Neoplasms; Buprenorphine; Corticosterone; Disease Models, Animal; Fentanyl; Hypothalamo-Hypophyseal System; Immune Tolerance; Killer Cells, Natural; Laparotomy; Lung Neoplasms; Male; Morphine; Neoplasm Metastasis; Neoplasms, Experimental; Pituitary-Adrenal System; Rats; Rats, Inbred F344; Stress, Physiological

The analgesic buprenorphine hydrochloride (Bph) induced apoptosis-like cell death in the caspase-3-deficient human breast cancer cell line, MCF-7. This apoptosis-like cell death activated key molecules in the mitochondrial apoptotic pathway: cytochrome c, caspase-9, caspase-7, and caspase-6. Bph caused the release of fluorescent protein from the mitochondria of MCF-7 cells transfected with the pDsRed2-Mito-vector in a time-dependent manner, suggesting disruption of the mitochondrial membrane. Zn(2+) as high as 2 mM did not inhibit the DNase that took part in this apoptosis. Thus, this unidentified DNase might resemble other DNases involved in apoptosis-like cell death whose activity is not inhibited by zinc ion.

Topics: Apoptosis; Blotting, Western; Breast Neoplasms; Buprenorphine; Caspases; Cell Line, Tumor; Cell Survival; Cytochromes c; Deoxyribonucleases; DNA Fragmentation; Enzyme Activation; Female; Humans; Mitochondria; Narcotic Antagonists; Transfection; Zinc

Three patients suffering from pain arising from renal and metastasing prostate and breast cancer were successfully treated with transdermal buprenorphine. The three cases demonstrate that transdermal buprenorphine is an easy-to-use and effective therapeutic option for the treatment of advanced cancer pain, that it can also be used in opioid rotation as an alternative after formerly applied steps II or III opioids have failed and that long-term treatment without dose escalation or compromise in tolerability is possible.

Topics: Administration, Cutaneous; Adult; Aged; Analgesics, Opioid; Breast Neoplasms; Buprenorphine; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Pain; Pain Measurement; Prostatic Neoplasms

We characterized anticancer effects of opioid analgesics that are clinically used for cancer patients for pain relief. Treatment with 100 microM buprenorphine, a representative analgesic, induced cell death of human carcinomas, such as A549 (squamous epithelial cell of lung cancer), MCF-7 (breast cancer) and N417 (small cell of lung cancer), but not in KATO III (gastric cancer) cells as evaluated by alamar blue assay. Among 18 clinically utilized and related analgesics, buprenorphine and loperamide showed potent inhibition of cell viability. However, these anti-cancer effects were not affected by opioid receptor antagonists nor by pertussis toxin. Buprenorphine-induced cell death occurred as early as 1 h after the addition, and its T1/2 of cell viability inhibition was 3 h. The cell death manifested the characteristics of apoptosis, such as DNA-laddering and nuclear fragmentation, which were sensitive to a caspase inhibitor, Z-Asp-CH2-DCB. The nuclear fragmentation was independent of cell cycle phase specificity. The activity of caspase-3-like protease which is known to be closely related to apoptotic DNA laddering was markedly enhanced by buprenorphine. However, the inhibition of cell viability by buprenorphine was not affected by the caspase inhibitor. These findings suggest that some opioid analgesics induce typical apoptotic features sensitive to the caspase inhibitor, while also inhibition of cell viability insensitive to the inhibitor.

Topics: Analgesics, Opioid; Apoptosis; Breast Neoplasms; Buprenorphine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Caspase 1; Caspase 3; Caspases; Cell Cycle; Cell Survival; DNA Fragmentation; Female; Flow Cytometry; Humans; Loperamide; Lung Neoplasms; Molecular Structure; Stomach Neoplasms; Tumor Cells, Cultured

This case-report of a 78-year old patient, suffering from extreme pain caused by metastatic formation and pathological bone fractures, shows, that the epidural injection of buprenorphine is a good alternative compared to other means of pain-treatment. During almost four days heart rate, blood pressure and breathing frequency, as well as the general reactions of the patient, were observed. Few side effects and little discomfort make the method advisable for patients in poor general condition.

Topics: Aged; Anesthesia, Epidural; Breast Neoplasms; Buprenorphine; Chronic Disease; Epidural Space; Female; Femoral Neck Fractures; Humans; Injections; Morphinans; Neoplasm Metastasis; Pain