Paul J. Daeninck

P53, MDM-2, BAX and BCL-2 and Drug Resistance in Chronic Lymphocytic Leukemia

Most antitumor agents exert their cytotoxic effect through the induction of apoptosis, and this process may be mediated through an elevation in p53 protein, with a subsequent increase in bax and decrease in bcl-2. p53 also increases mdm-2 expression and mdm-2 may then bind and inactivate p53. Cells from 31 patients with chronic lymphocytic leukemia (CLL) were treated in vitro with 2-chlorodeoxyadenosine (CdA), arabinosyl-2-fluoroadenine (F-ara-A), or chlorambucil (CLB) and drug sensitivity measured using the MTT assay. The protein levels of bax and bcl-2 were measured in CLL cells from 25 patients, and were found to be higher in leukemic cells than in normal B cells. The bcl-2 levels varied three-fold, the bax levels fifteen-fold, and the bax:bcl-2 ratios ranged from 0.44 to 2.91. The expression of mdm-2 mRNA was measured in CLL cells from 28 patients and was found to vary twenty-fold. However, no correlation was observed between drug sensitivity to CdA, F-ara-A, or CLB and the cellular levels of mdm-2 mRNA, or the protein levels of bax or bcl-2, or the bax:bcl-2 ratio. Treatment of CLL cells having wild type p53 with CdA, F-ara-A or CLB produced an increase in p53 protein and mdm-2 mRNA. This was not observed in cells having a p53 mutation, and these cells were highly resistant to both CLB and the nucleoside analogs. In contrast to the nucleoside analogs and CLB, dexamethasone and vincristine had no effect on mdm-2 mRNA levels. Treatment of CLL cells containing a wild type p53 gene with CdA, F-ara-A, or CLB, did not produce any consistent changes in bax or bcl-2. Thus, CdA, F-ara-A and CLB appear to act in CLL cells through a p53-dependent pathway, whereas this does not occur with dexamethasone or vincristine. The cellular levels of mdm-2, bcl-2, bax or the bax:bcl-2 ratios are not predictive indicators of clinical sensitivity in CLL, but an increase in mdm-2 levels after drug treatment is indicative of p53 function in these cells.

A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) in cancer patients places a significant burden on patients’ function and quality of life, their families and caregivers, and healthcare providers. Despite the advances in preventing CINV, a substantial proportion of patients experience persistent nausea and vomiting. Nabilone, a cannabinoid, recently received Food and Drug Administration approval for the treatment of the nausea and vomiting in patients receiving cancer chemotherapy who fail to achieve adequate relief from conventional treatments. The cannabinoids exert antiemetic effects via agonism of cannabinoid receptors (CB1 and CB2). Clinical trials have demonstrated the benefits of nabilone in cancer chemotherapy patients. Use of the agent is optimized with judicious dosing and selection of patients.

The emerging role of cannabinoid neuromodulators in symptom management

IntroductionThe cannabinoids nabilone (Cesamet) and dronabinol (Marinol) are indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in cancer patients who have failed to respond adequately to conventional antiemetic therapy.DiscussionThe endocannabinoid (CB) system interacts with numerous other systems and pharmaceutical cannabinoids target ubiquitous CB1 and CB2 receptors in the central nervous system and periphery, relieving nausea and vomiting and pain.SummaryThe benefits of this novel class of medications in cancer may extend beyond CINV, as indicated by data from preclinical studies and animal models.

Pilot Study of a Survey to Identify the Prevalence of and Risk Factors for Chronic Neuropathic Pain Following Breast Cancer Surgery

PURPOSE/OBJECTIVES To provide a preliminary determination of the prevalence rate of women who suffer from neuropathic pain post breast surgery (PPBS) and explore potential risk factors associated with its development. DESIGN Prospective, quantitative, longitudinal survey. SETTING Breast health clinic in western Canada. SAMPLE A convenience sample of 17 women undergoing breast cancer surgery. METHODS The Brief Pain Inventory was administered before surgery and 2 days, 10 days, and 3 months postsurgery. Demographic data also were collected preoperatively. Analysis included determining prevalence of PPBS; descriptive analyses on age, gender, and body mass index (BMI); presence of acute postoperative pain; type of surgery; and two-tailed t tests on age and BMI. MAIN RESEARCH VARIABLES The symptom experience of chronic PPBS. FINDINGS Twenty-three percent of the sample developed PPBS. Younger age (50 years or younger), more invasive surgery, acute postoperative pain, and less analgesic use during the acute postoperative period were factors associated with the development of PPBS. CONCLUSIONS Additional research is required to confirm the significance of these potential risk factors in the development of PPBS. IMPLICATIONS FOR NURSING Nurses are ideally situated to identify early signs of PPBS. In addition, nurses play a key role in the education of patients and healthcare professionals and can facilitate increased awareness about the possibility of developing PPBS, enabling earlier and more effective treatment of PPBS.

Multiple Myeloma Presenting Clinically as Lymphoma

Multiple myeloma typically presents with monoclonal proteinemia, marrow plasmacytosis, anemia, bony involvement, hypercalcemia and renal insufficiency. Less frequent presentations include hepatic and splenic enlargement (5% of cases), lymphadenopathy (4%) and biclonal gammopathy (1%). Chemotherapy may produce remissions in 50% of cases, but relapses are the rule and mean survival is approximately 2.5 years. To improve survival, marrow transplantation is being explored as a therapeutic modality in younger patients. In this report we describe a unique case of multiple myeloma presenting clinically as lymphoma. The patient presented with fever, widespread lymphadenopathy and pleuropulmonary involvement and responded promptly to multiagent doxorubicin-based chemotherapy. This was followed by high-dose chemotherapy and allogeneic bone marrow transplantation and the patient remains in remission more than 36 months post transplant. This case report suggests that myeloma simulating lymphoma may be a chemosensitive and potentially curable myeloma variant.