Information from the Internet: attitudes of Australian oncology patients.

BACKGROUND: Patients require accurate information about their illness to make informed decisions. Many sources of information exist, although reliability is variable. Our objective was to investigate information seeking behaviour and attitudes toward health-related information from the Internet in a sample of Australian oncology patients. METHOD: During their outpatient attendance, 109 patients completed a self-administered paper-pen format questionnaire. They were required to have a recent cancer diagnosis (<6 months ago) adequate English and no cognitive impairment. RESULTS: Seventy-four per cent of questionnaires were returned. The majority of patients (78%) wanted as much information about their cancer diagnosis as possible and 90% reported receiving adequate information from their treating team. Despite this, more than half actively searched for additional information, with 77% using the Internet. Patients were trusting of information obtained from the Internet. More than half of information searchers discussed information obtained in their search with a health professional. The majority of patients did not believe that information searching adversely affected the doctor-patient relationship. CONCLUSION: Information searching is common in ambulatory Australian oncology patients, with the Internet being a frequently used resource. To ensure patients find reliable and relevant information and to minimize the risk of harm, health professionals involved in treating oncology patients should provide guidance in finding information sources and assistance in interpreting the information obtained.

Photorhabdus virulence cassettes confer injectable insecticidal activity against the wax moth.

Two recently sequenced genomes of the insect-pathogenic bacterium Photorhabdus and a large Serratia entomophila plasmid, pADAP, have phage-related loci containing putative toxin effector genes, designated the "Photorhabdus virulence cassettes" (PVCs). In S. entomophila, the single plasmid PVC confers antifeeding activity on larvae of a beetle. Here, we show that recombinant Escherichia coli expressing PVC-containing cosmids from Photorhabdus has injectable insecticidal activity against larvae of the wax moth. Electron microscopy showed that the structure of the PVC products is similar to the structure of the antibacterial R-type pyocins. However, unlike these bacteriocins, the PVC products of Photorhabdus have no demonstrable antibacterial activity. Instead, injection of Photorhabdus PVC products destroys insect hemocytes, which undergo dramatic actin cytoskeleton condensation. Comparison of the genomic organizations of several PVCs showed that they have a conserved phage-like structure with a variable number of putative anti-insect effectors encoded at one end. Expression of these putative effectors directly inside cultured cells showed that they are capable of rearranging the actin cytoskeleton. Together, these data show that the PVCs are functional homologs of the S. entomophila antifeeding genes and encode physical structures that resemble bacteriocins. This raises the interesting hypothesis that the PVC products are bacteriocin-like but that they have been modified to attack eukaryotic host cells.

The insecticidal toxin Makes caterpillars floppy (Mcf) promotes apoptosis in mammalian cells.

Photorhabdus bacteria produce a number of toxins to kill their insect hosts. The expression of one of these, Makes caterpillars floppy (Mcf), is sufficient to allow Escherichia coli to persist within and kill caterpillars. Mcf causes shedding of the insect midgut epithelium and destructive blebbing of haemocytes suggesting it may trigger apoptosis. To investigate this hypothesis, here we examine the effects of E. coli-expressed Mcf on the mammalian cell lines COS-7, NIH 3T3 and HeLa cells. Cells treated with Mcf show apoptotic nuclear morphology, active caspase-3, DNA laddering after 6 h, and the presence of cleaved PARP after 16 h. These effects are prevented by the apoptosis inhibitor zVAD-fmk. Transfection of cells with constructs expressing only the NH2-terminal 1280 amino acids of Mcf, as a fusion with Myc, also triggered cell destruction. The expressed fusion protein was concentrated into the Golgi apparatus before cell death. These results confirm that the novel insecticidal toxin Mcf induces apoptosis but the precise intracellular pathway remains obscure.

A retrospective analysis of the relationship between changes in serum PSA, palliative response and survival following systemic treatment in a Canadian randomized trial for symptomatic hormone-refractory prostate cancer.

BACKGROUND: To investigate the relationship between changes in serum PSA, palliative response and survival following systemic treatment for symptomatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A retrospective review of 161 patients, treated with mitoxantrone and prednisone (M + P) (n = 80), or prednisone alone (P) (n = 81) from a Canadian randomized phase III clinical trial. PSA response was defined by > or =50% decline compared to baseline. Palliative response was defined by the primary and secondary endpoints of the trial. All responses were required to be maintained on two visits at least three weeks apart. The Cox proportional hazards model and a landmark analysis (at nine weeks) were used to evaluate survival differences between PSA responders and non-responders. RESULTS: Using an intent-to-treat analysis in which patients with missing PSA data are considered non-responders, 34% of M + P and 11% of P patients achieved a PSA response (P = 0.0001). Nineteen of thirty-six (53%) patients with PSA response and twenty-six of ninety (29%) patients without PSA response achieved a palliative response (P = 0.001 Chi-square test, phi coefficient = 0.28). From the landmark analysis. PSA responders had longer survival than non-responders (P = 0.009). In multivariate analysis, better performance status, higher hemoglobin and PSA response (P < 0.001) predicted for survival, but palliative response did not (P = 0.11). CONCLUSIONS: There is significant but imperfect statistical association between PSA response and palliative response. PSA response was associated with longer survival. Patients treated with M + P were more likely to achieve a PSA response and a palliative response than those treated with P.

High-dose therapy and autologous transplantation for lymphoma: The Peter MacCallum Cancer Institute experience.

BACKGROUND: High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. AIM: To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). METHODS: A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). RESULTS: Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P = 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%). There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P= 0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. CONCLUSION: HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further.

Perception of quality of life by patients, partners and treating physicians.

The objective of the study was to determine possible differences in perception of quality of life (QoL) between patients with metastatic breast or prostate cancer, their partners, and the treating physician. Patients with metastatic breast cancer (n = 71), and metastatic prostate cancer (n = 29), a partner, and the physician each completed the same QoL questionnaire indicating how they perceived the patient's QoL. The European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire was used to assess patients with breast cancer and the modified prostate cancer specific quality of life instrument (PROSQOLI) for patients with prostate cancer. There was reasonable agreement in mean scores between patients, and physicians or partners, for many domains of QoL; however, there was substantial discordance between scores when considering individual patients. For patients with metastatic breast cancer, physicians systematically underestimated overall QoL (p = 0.0002), social functioning (p = 0.001), and role functioning (p = 0.008), while partners showed better agreement. With prostate cancer physicians tended to underestimate pain, while mean scores for spouses were more concordant. There is substantial variability between ratings of QoL by physicians or partners, as compared to patient ratings. Medical decisions should be based on information about QoL provided by patients using validated methods.

Prostate specific antigen response to mitoxantrone and prednisone in patients with refractory prostate cancer: prognostic factors and generalizability of a multicenter trial to clinical practice.

PURPOSE: We determine prostate specific antigen (PSA) response and durability, and prognostic factors associated with response and survival in patients with symptomatic hormone refractory prostate cancer treated with mitoxantrone and prednisone at a single institution. We then compare the results with those of a randomized phase III clinical trial. MATERIALS AND METHODS: A retrospective review of all 133 patients treated with mitoxantrone and prednisone at Princess Margaret Hospital since 1994 was performed. PSA response and duration, and overall survival were determined as well as the influence of baseline factors on these outcome parameters. Results were compared to those for patients randomized to receive mitoxantrone and prednisone in the Canadian clinical trial which demonstrated palliative benefit of this regimen. RESULTS: Patients treated after trial closure had shorter survival (p = 0.003) but represented a poorer prognosis cohort. PSA response of the trial and post-trial cases was 34% and 28%, respectively (p = 0.36), and median duration of response was 118 and 175 days or greater, respectively. Factors predictive of PSA response in the non-trial cohort were longer time from diagnosis of prostate cancer (p = 0. 027) and higher baseline PSA (p = 0.013). Factors predictive of increased survival in both groups were younger age (p <0.04), better baseline Eastern Cooperative Oncology Group performance status (p <0. 02), and higher hemoglobin (p