S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS

BACKGROUND: This study reports on clinical data from an 8-week open-label study of 20 HIV-seropositive individuals, diagnosed with Major Depressive Disorder (DSM-IV), who were treated with SAM-e (S-Adenosylmethionine). SAM-e may be a treatment alternative for the management of depression in a population reluctant to add another "pill" or another set of related side effects to an already complex highly active antiretroviral therapy (HAART) regimen. METHODS: The Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory (BDI) were used to assess depressive symptomatology from 1,2,4,6 and 8 weeks after initiation of treatment with SAM-e. RESULTS: Data show a significant acute reduction in depressive symptomatology, as measured by both the HAM-D and the BDI instruments. CONCLUSIONS: SAM-e has a rapid effect evident as soon as week 1 (p < .001), with progressive decreases in depression symptom rating scores throughout the 8 week study

Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

<p>Abstract</p> <p>Background</p> <p>Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting.</p> <p>Objective</p> <p>To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method.</p> <p>Methods</p> <p>We cultured myeloma-positive CD34⁺PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34⁺cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture.</p> <p>Results</p> <p>Overall recovery of CD34⁺cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34⁺cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34⁺cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34⁺cell selection, and up to 2.3 logs after culture and ΔNGFR selection.</p> <p>Conclusion</p> <p>We conclude that <it>ex-vivo </it>culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.</p

Bcl-6 protein expression, and not the germinal centre immunophenotype, predicts favourable prognosis in a series of primary nodal diffuse large B-cell lymphomas: a single centre experience.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL have been proposed as a practical method to validate and surrogate results obtained by gene expression profiling. We studied 71 patients with primary nodal DLBCL at diagnosis, who received anthracycline-based therapy with or without rituximab. Immunohistochemistry was performed using anti-CD10, Bcl-6, MUM1 and Bcl-2 antibodies in order to assess the ontogenic profile of neoplastic cells and to verify its relation with clinical outcome. Survival data were analysed using an explorative Cox model. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL were not associated with prognosis. By contrast, Bcl-6 expression was associated with a longer lymphoma-free survival while immunoreactivities for MUM1 or Bcl-2 were not significantly related to patient outcome. Bcl-6 expression alone proved to be a prognostic marker in primary nodal DLBCL and seemed to be more reliable to predict clinical outcome in these disorders than the immunohistochemical algorithms for the detection of the germinal centre/non-germinal centre immunophenotype

Capecitabine in Breast Cancer: the issue of cardiotoxicity during fluoropyrimidine treatment

Capecitabine is an orally available fluoropyrimidine carbamate that selectively delivers fluorouracil (5-FU) to tissues expressing high levels of thymidine phosphorylase (TP) such as tumors. The drug has demonstrated efficacy in metastatic breast cancer, colorectal, and pancreatic cancer. Although these are considered safe drugs, a growing body of literature reports adverse cardiac effects. Clinical trials indicate that capecitabine has a cardiac toxicity similar to that of infused fluoropyrimidines such as 5-FU. Here, we review cardiotoxicity in the use of fluoropyrimidines, with particular attention toward capecitabine. We also describe a severe, reversible cardiac event that occurred in a 39-year-old woman, with no cardiac risk factors, treated with capecitabine for advanced breast cancer. This review and our experience confirm that fluoropyrimidine cardiotoxicity is an infrequent but documented side effect. Oncology patients under treatment should be closely observed and monitored for cardiac symptoms with particular attention in case of signs or symptoms of cardiovascular complications. The implementation of cardio-oncology interdisciplinary teams should, in the future, reduce the impact of cancer treatment\u2013associated cardiotoxicity syndromes

Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

BACKGROUND: Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting. OBJECTIVE: To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method. METHODS: We cultured myeloma-positive CD34+ PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34+ cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, DeltaNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture. RESULTS: Overall recovery of CD34+ cells after culture was 128.5%; DeltaNGFR transduction rate was 28.8% for CD34+ cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34+ cells after DeltaNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7-1.4 logs in tumor load after the CD34+ cell selection, and up to 2.3 logs after culture and DeltaNGFR selection. CONCLUSION: We conclude that ex-vivo culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging

Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients Aged &#8805; 75 Years With Non&#8211;small-cell Lung Cancer (NSCLC) : An Italian, Multicenter, Retrospective Study

Introduction: Non\u2013small-cell lung cancer (NSCLC) is predominantly a disease of the elderly population. Over the past few years, immunotherapy with monoclonal antibodies named checkpoint inhibitors (ICIs) greatly improved the clinical management of a significant proportion of patients with metastatic NSCLC. However, pivotal trials excluded older patients, although, given the favorable clinical profile of ICIs, this treatment may be revealed to be a most valuable option also for these patients. To this aim, a multicenter retrospective analysis was performed on patients aged 65 75 years with NSCLC treated with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy. Material and Methods: Inclusion criteria were: diagnosis of locally advanced or metastatic NSCLC (stage IIIB or IV, according to the American Joint Committee on Cancer (AJCC) classification system, version 8.0); age 65 75 years; treatment with anti-PD-1/PD-L1 monoclonal antibodies in first or subsequent lines of treatment; absence of epidermal growth factor receptor-activating mutations or anaplastic lymphoma kinase and ROS-1 rearrangements. The primary endpoints of the study were the efficacy, in terms of overall response rate, progression-free survival, and overall survival, and safety, by means of evaluations of the incidence of immune-related adverse events. Results: Eighty-six patients were considered for the final analysis; 71 (82.6%) were male. The mean age was 78.5 years (range, 75-86 years; SD, 3.12 years). Of the 86 patients, 69 (80.2%) of patients had a performance status of 0 or 1. The overall median progression-free survival was 5.6 months (range 1-36 months; SD, 7.5 months,) whereas the median overall survival was 10.1 months (range, 1.7-34.8 months; SD, 8 months). At the Cox regression analysis, the only parameter significantly associated with survival was the smoking status (P = .008). No difference in survival was found between patients younger and older than 80 years. Conclusions: In the present real-world retrospective cohort, efficacy and toxicity profiles of ICIs in older patients with advanced NSCLC were comparable with those observed in younger patients enrolled in clinical trials. This study was conducted in the setting of advanced non\u2013small-cell lung cancer in older patients. It is a multicenter retrospective analysis on very old persons that explores the efficacy and the safety of anti-programmed cell death protein 1 therapy. Older patients seem to tolerate immunotherapy as well as younger patients with comparable efficacy. This is a relevant message for everyday clinical practice