Is digitalis a therapy for breast carcinoma?

We have previously reported effects on breast carcinoma by digitalis on patients in vivo with significant effects on cytometric features and recurrence rate. Increased attention is now paid to the anti-proliferative and apoptosis inducing effect on cancer cells in vitro by glycosides from foxglove as well as by some other glycosides. The present study is a long-term follow-up (22.3 years) of 175 patients with breast carcinoma, of which 32 were on digitalis treatment, when they acquired their breast carcinoma. There was a lower death rate (6%) from breast carcinoma among the patients on digitalis, when compared with patients not on digitalis (34%). Also proliferation/aneuploidy was less pronounced of the tumors in patients on digitalis. These observations were statistically significant although the statistical analysis was hampered in the life-table analysis by the fact that only 2/32 patients on digitalis died from breast cancer. Serious consideration should be given to the effects of digitalis derivatives on cancer cells in cancer drug design. This field of research is not sufficiently explored and holds promise to contain drugs superior to present-day adjuvant therapy both with respect to effects and side-effects.     

Is there a general autoantibody signature for cancer?

BackgroundThere is longstanding evidence for the diagnostic potential of single autoantibodies for cancer and other diseases and more recently for the potential of complex autoantibody signatures. Here we address the question whether cancer specific signatures exist.MethodsWe analysed our autoantibody screening data both newly and previously generated using a single array platform with 1827 identified immunogenic clones. These clones were tested for their reactivity against a total of 428 human sera including 191 sera of patients with different cancer entities, 60 sera of healthy individuals and 177 sera of patients with non-cancer diseases by using bioinformatics approaches.ResultsPrincipal Component Analysis and hierarchical clustering revealed significant differences between the three cohorts. Evaluating the autoantibody reactivities in the three groups using Support Vector Machines, we were able to separate cancer sera from normal sera with an accuracy of 94.08%. A pathway analysis that was based on antigens with an increased reactivity in patients’ sera as compared to controls indicated glycolysis as central pathway. The separation between cancer and non-cancer disease sera was possible with an accuracy of only 69.58%, which is still significantly higher than by random classification.ConclusionAs for single autoantigens, we show that proteins that are frequently reactive with cancer sera are also frequently reactive with non-cancer sera. While these results underline the potential of autoantibody signatures for cancer diagnosis, they also caution to premature claim specificity of a signature.     

Is There a Place for Screening Flexible Sigmoidoscopy?

Flexible sigmoidoscopy is a valid screening tool for the early detection of colorectal cancer (CRC). Recently published long-term data from UKFSST, a randomized controlled trial, demonstrate a 33% reduction in colorectal cancer incidence and a 43% decrease in colorectal cancer mortality, with once-in-a-lifetime screening. On the other hand, data from the NORCCAP trial with a similar protocol show no reduction in CRC incidence and only nonsignificant decrease in CRC mortality at 7 years. At best, flexible sigmoidoscopy can detect only 70% of cancers and polyps as it does not detect the 40% of proximal neoplasms which are not associated with a distal lesion. The advantage of flexible sigmoidoscopy over other screening modalities lies in its safety profile, patient tolerance, and overall acceptance. Its technical simplicity, short duration, and cost-effectiveness advance its applicability to mass screening programs.     

Is there a role for a specialized follow-up clinic for survivors of pediatric cancer?

Due to advances in chemotherapy and supportive care, greater than 70% of patients with childhood cancer will survive 5 years. However, there are long-term physiological and psychological sequelae of these treatments that may not manifest until pediatric survivors are into adulthood. Various studies done in the long-term pediatric survivors have noted that they are at increased risk for poor health and for chronic health problems. One complicating factor in treating these patients for their health problems is that many childhood cancer survivors are unaware of their past medical history and what their past cancer treatment entailed. There are also a number of barriers to medical care in survivors of childhood cancer which include inadequate insurance coverage for many and lack of knowledge of long-term effects physicians. As pediatric cancer survivors age they usually transition to community physicians. This paper proposes different models for follow-up clinics for survivors of pediatric cancers so childhood cancer survivors are not be subjected to cost ineffective or excessive evaluations but rather medical screening tests that are risk and guidelines that are set forth by experts.     

Is Dexamethasone a Better Partner for Abiraterone Than Prednisolone?

Dexamethasone may be a better partner for abiraterone compared with prednisolone in the treatment of metastatic castration-resistant prostate cancer. Upfront use of dexamethasone with abiraterone or a switch from prednisolone to dexamethasone at prostate-specific antigen progression might be feasible options and are currently being tested in larger trials.I read with great interest the article by Auchus et al. [1] in which they comprehensively reviewed the use of prednisone with abiraterone acetate in the treatment of metastatic castration-resistant prostate cancer (CRPC). Although prednisolone is the most commonly used corticosteroid with abiraterone in clinical trials and is the standard of care as recommended by current guidelines, two recent trials have shown better response rates and progression-free survival with dexamethasone compared with prednisolone. In the first trial, Lorente et al. [2] showed that durable prostate-specific antigen (PSA) responses might be achieved with a switch from prednisolone to dexamethasone (0.5 mg/day) in patients progressing on abiraterone. In patients with CRPC and progressive disease with abiraterone-prednisolone, 11 of 30 patients (39%) had confirmed ≥30% PSA decline after switching to dexamethasone with median time to PSA progression of 11.7 weeks. These results are comparable with the response rate (41%) and duration (2.8 months) with enzalutamide after abiraterone in CRPC treatment [3].The second trial is a randomized phase 2 trial that compared the efficacy of prednisolone (5 mg b.i.d.) and dexamethasone (0.5 mg/day) in chemotherapy-naïve patients with CRPC. In evaluable patients, the PSA response rates were 47% versus 24% for dexamethasone and prednisolone, respectively (p = .05). Median time to PSA progression was 9.7 months on dexamethasone versus 5.1 months on prednisolone (hazard ratio, 1.6; 95% confidence interval, 0.9–2.8). Among patients who crossed over at PSA progression on prednisolone, 37% had a confirmed PSA response to dexamethasone [4]. Pharmacokinetic and pharmacodynamic differences between dexamethasone and prednisolone might partially explain this phenomenon. The half-life of dexamethasone is longer, which may result in more effective suppression of adrenocorticotropic hormone and more proficient antitumoral activity. Second, abiraterone inhibits CYP 3A4, decreases the clearance, and further increases the half-life of dexamethasone, whereas prednisolone is usually not affected [5]. On the other hand, differences in the activity of synthetic glucocorticoids at the glucocorticoid receptor level might also cause alterations in efficacy [6].In conclusion, dexamethasone may be a better partner for abiraterone compared with prednisolone. Upfront use of dexamethasone with abiraterone or a switch from prednisolone to dexamethasone at PSA progression might be feasible options and are currently being tested in larger trials (ClinicalTrials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT01867710","term_id":"NCT01867710"}}NCT01867710, Abiraterone With Different Steroid Regimens for Side Effect Related to Mineralcorticoid Excess Prevention in Prostate Cancer Prior to Chemotherapy).     

Is there a role for chemotherapy in prostate cancer?

There is evidence from randomised-controlled trials that patients with symptomatic hormone-refractory prostate cancer may experience palliative benefit from chemotherapy with mitoxantrone and prednisone. This treatment is well tolerated, even by elderly patients, although the cumulative dose of mitoxantrone is limited by cardiotoxicity. Treatment with docetaxel or paclitaxel, with or without estramustine, appears to convey higher rates of prostate-specific antigen response in phase II trials, but is more toxic. Large phase III trials comparing docetaxel with mitoxantrone have completed accrual. There is no role for chemotherapy in earlier stages of disease except in the context of a well-designed clinical trial.     

Is age a risk factor for Candida glabrata colonisation?

Studies have reported that Candida glabrata infections are more common in older adults. We sought to determine colonisation rates of C. glabrata in the oral cavity and its relationship with age, comorbid illnesses and hospital or extended care facility stay. Samples were obtained from four sites in the oral cavity and from dentures, when available, from 408 subjects from the community (136), hospital (126) or an extended care facility (146). Overall, 219 (53.7%) subjects were colonised with yeast; the predominant species was Candida albicans. Sixty‐two patients (15.2%) were colonised with C. glabrata. None of the subjects <40 years was colonised with C. glabrata; in those from the community, only nine persons, all of whom were >60 years, were colonised with C. glabrata. By multivariate analysis, increasing age, dentures and use of psychotropic medications were independently associated with C. glabrata colonisation; residing in the community, rather than hospital or extended care, was strongly protective against colonisation. Candida glabrata colonisation is multifactorial; age, and hospitalisation/extended care stay contribute to colonisation. Dentures are strongly associated with colonisation with any yeast and with C. glabrata. Further study is needed to evaluate the relationship of these findings to increasing C. glabrata infections in older adults.     

Is there a need for axillary dissection in breast cancer?

The involvement of axillary nodes remains a significant prognostic factor in breast cancer. However, management has changed from complete surgical staging to sentinel lymph node biopsies. Although little controversy exists regarding patients with negative sentinel lymph node biopsies, some remains regarding what to do with patients with small volume of axillary disease. This article focuses on the examination of recent evidence in management of the axilla. It focuses on both the prognostic and therapeutic information gleaned from isolated tumor cells and micrometastatic disease and on the use of completion axillary lymph node dissections or axillary radiation in preventing regional recurrence.     

Is there a cloud in the silver lining for imatinib?

Imatinib mesylate (Gleevec) or Glivec), a small molecule tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia, has been said to herald the dawn of a new era of rationally designed, molecularly targeted oncotherapy. Lurking on the same new horizon, however, is the age-old spectre of drug resistance. This review sets the intoxicating clinical perspective against the more sobering laboratory evidence of such divergent mechanisms of imatinib resistance as gene amplification and stem cell quiescence. Polychemotherapy has already been considered to combat resistance, but a more innovative, as yet unformulated, approach may be advocated.