The Role of Panobinostat Plus Bortezomib and Dexamethasone in Treating Relapsed or Relapsed and Refractory Multiple Myeloma: A European Perspective

Article full text The full text of this article can be found here. Provide enhanced digital features for this article If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact [email protected]. The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content. Other enhanced features include, but are not limited to: • Slide decks • Videos and animations • Audio abstracts • Audio slides</p

Additional file 1: of Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus

Figure S1. Dot Plot visualizing the purity of NK cells after negative isolation by MACS. PBMCs before (PBMC) and after (PBMC w/o NK cells) NK cell isolation were analyzed for NKp46 (NK cells), CD14 (MØ), CD3 (T cells) and CD19 (B cells) expression. Isolated NK cells were also included in the analysis before subsequent experiments. One representative result is shown, results were rounded to the nearest whole number. Purity of isolated NK cells was always above 95%. (PDF 1454 kb

Silencing of CDK2, but not CDK1, separates mitogenic from anti-apoptotic signaling, sensitizing p53 defective cells for synthetic lethality

<p>Small molecule inhibitors targeting CDK1/CDK2 have been clinically proven effective against a variety of tumors, albeit at the cost of profound off target toxicities. To separate potential therapeutic from toxic effects, we selectively knocked down CDK1 or CDK2 in p53 mutated HACAT cells by siRNA silencing. Using dynamic, cell cycle wide proteome arrays, we observed minor changes in overall abundance of proteins critically involved in cell cycle transition despite profound G₂/M or G₁/S arrest, respectively. Employing phospho site specific analyses, we identified uncoupled mitogenic, yet pro-apoptotic signaling from counter balancing anti-apoptotic activity in CDK2 disrupted cells. Moreover, a crucial role of CDK2 activity in early serum response was observed, extending well-established roles of CDKs outside their cell cycle regulating functions. In contrast, disruption of CDK1 only marginally affected phosphorylation events of crucial signaling nodes prior to G₂/S transition. The data presented here suggest that the temporal separation of pro- and anti-apoptotic pathways by selective inhibition of CDK2 disrupts coherent signaling modules and may synergize with anti-proliferative drugs, averting toxic side effects from CDK1 inhibition.</p

Additional file 1 of The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: a prospective observational study

Additional file 1: Supplementary Table 1. Sociodemographic and clinical characteristics of the 70 patients with MM included in the study. Supplementary Table 2. P-values and mean-values. Supplementary Table 3. Summary of the most important results. Supplementary Table 4. Therapy of patients without stem cell transplantation. Supplementary Table 5. Therapy of patients with stem cell transplantation

Data_Sheet_1_Mind–body-medicine in oncology—from patient needs to tailored programs and interventions: a cross-sectional study.DOCX

IntroductionNational and international guidelines recommend early integration of evidence-based multimodal interventions and programs, especially with a focus on relaxation techniques and other Mind–Body-based methods to maintain the quality of life of oncology patients, improve treatment tolerability, and promote healthy lifestyle behaviors. Consequently, we aim to understand what drives patients and how they navigate integrative medicine to best advise them. This study aimed to detect possible topics of particular interest to patients and identify the patient groups that could benefit most from further programs. Furthermore, we aimed to investigate if patients are open-minded toward integrative oncology concepts and learn about their motivational level to maintain or change behavior.MethodsBetween August 2019 and October 2020 we surveyed patients undergoing oncological therapy in a university oncological outpatient center using a custom-developed questionnaire based on established Mind–Body Medicine concepts.ResultsWe included 294 patients with various cancers. More than half reported problems sleeping through (61%) and 42% felt stressed frequently, invariably rating this as detrimental to their health. Moreover, a slight majority (52%) felt physically limited due to their disease and only 30% performed defined exercise programs. Women were significantly more likely to feel stressed and reported with alarming frequency that they often feel “everything was up to them.” The 40–65-year-olds reported significantly less restful sleep, more stress and were more dissatisfied with their situation. However, this group already used natural remedies most frequently and was most often motivated to use relaxation techniques in the next 6 months. The lower the perceived individual energy level (EL), the less frequently patients did sport, the more frequently they felt their disease impaired their activity, mostly feeling stressed and tense. We also found significant associations between negative emotions/thoughts and the variables “sleep,” “use of relaxation techniques,” “personal stress perception,” and “successful lifestyle modification.”ConclusionMind–Body programs that focus on patient’s individual resources, with tools to explore impairing patterns of self-perception and cognitive biases, can be a valuable resource for oncology patients and should therefore be part of an integrative medical treatment concept.</p

Additional file 1 of Needs of amyloidosis patients and their care providers: design & first results of the AMY-NEEDS research and care program

Additional file 1. Table 1: Categories

Impulse response functions (IRF) plotting the evolution of the model parameters after a simulated increase in CRP.

The IRF models the exogenous increase in CRP induced by a one-standard-deviation impulse to the error-term in the CRP regression. Upper left panel shows the effects on AP: A significant and initially accumulating increase in periods 0 and 1 is apparent, which slowly returns to normal after 8 periods (48 days). Upper left panel shows the effects on CRP: Observable is an instantaneous significant increase in period 0, which returns to normal after 5 periods (30 days). Lower left panel shows the effects on NT-proBNP: There are no statistically significant effects. Lower right panel shows the effects on proteinuria: Observable is a significant and initially accumulating increase in periods 0, 1 and 2 which slowly returns to normal after 8 periods (48 days).</p

Tracking cardiac response by serial ¹⁸F-Florbetaben-PET/CT—Times series of retention indices measured by serial ¹⁸F-Florbetaben-PET/CT in comparison to cardiac biomarker NT-proBNP.

NT-proBNP values (black line) decrease continuously over time with short-term fluctuations. Retention indexes (dotted line) map the long-term course in a similar way. The time points of tocilizumab application are noted by means of black dots.</p

Serum dependence of SGK3 depleted MM cells.

<p>MM cells transfected with either stealth siRNA against EGFP (white columns) or against SGK3 (grey columns) were washed three times with PBS at day 2 post-electroporation and resuspended in fresh medium, subsequently adjusted to contain the indicated concentrations of FBS. After further culture for 3 days cell death was determined by annexin V/PI staining and FACS analysis. Error bars indicate s.e.m. based on 4 independent experiments.</p

SGK3 knockdown in combination with Akt inhibition.

<p>A) Titration of allosteric Akt inhibitors MK-2206 and Akti1,2. MM cells were incubated with the drugs for 30 min prior to harvest for Western blotting. B) Dose-effect curves representing cell death (annexin V) or viability (alamarBlue) assays for MM.1s cells (left), L-363 cells (middle) and AMO-1 cells (right) from either untreated cultures (blue dots), cells electroporated with stealth siRNA against EGFP (green dots) or cells electroporated with stealth siRNA against SGK3 (red dots), and treated with various concentrations of MK-2206 for 3 days. Drugs were added to electroporated cells at day 2 post-electroporation. Cells from untreated cultures were kept at similar densities as those of electroporated cells prior to drug addition. Each dose/effect curve is based on between 3 and 4 independent experiments. Error bars indicate s.e.m. C) Same experimental setup as described in B) but with Akt inhibitor Akti1,2. Each dose/effect curve is based on between 2 and 3 independent experiments. Error bars indicate s.e.m.</p