Adding bendamustine to melphalan before ASCT improves CR rate in myeloma vs. melphalan alone: A randomized phase-2 trial.

Definite cure remains exceptional in myeloma patients even after high-dose chemotherapy (HDCT) with melphalan (Mel) and autologous stem cell transplantation (ASCT). Thus, improving efficacy of HDCT in MM remains an unresolved issue. This randomized phase II trial compared standard 200 mg/m Mel HDCT to experimental HDCT with 200 mg/m bendamustine, given both at days -4 and -3, combined with 100 mg/m melphalan at days -2 and -1 (BenMel) before ASCT as first-line consolidation in myeloma patients.

[The use of immune checkpoint inhibitors in routine oncology].

Background: The advent of immune checkpoint inhibitors has dramatically changed the treatment landscape of many different tumor types. In the clinical routine, humanized antibodies against the immune checkpoints cytotoxic T‑lymphocyte associated protein 4 (CTLA-4) and programmed cell death 1/programmed cell death ligand 1 (PD1/PD-L1) are generally applied.

Objective: This article provides an overview of the treatment landscape with immune checkpoint inhibitors, especially for solid tumors in oncology.

Swiss experience of atezolizumab for platinum-pretreated urinary tract carcinoma: the SAUL study in real-world practice.

Aims Of The Study: Atezolizumab is an approved therapy for urothelial carcinoma based on results from the IMvigor 210 and IMvigor211 phase II and III trials. The global SAUL study evaluated atezolizumab in a broader patient population more representative of real-world populations. Among approximately 1000 patients treated in SAUL, 25 were treated in Swiss oncology centres.

[Immunotherapies - Overview, mode of action and clinical implications].

Immunotherapies - Overview, mode of action and clinical implications The introduction of immunotherapies has led to major advances in the treatment of cancer patients. The mainstays of immunotherapies in clinical routine are immune checkpoint inhibitors. Immune checkpoints like CTLA-4 or the PD-1 / PD-L1 axis are important contributors to the immune homeostasis by preventing overshooting immune responses against pathogens and thus preventing collateral damage to normal tissue, or by preventing autoimmunity.

Solid cancer development in solid organ transplant recipients within the Swiss Transplant Cohort Study.

In solid organ transplant recipients (sOTRs), 5 years after transplantation cancer is a relevant cause of death. We aimed to report cancer incidence in the Swiss Transplant Cohort Study (STCS) between 2008 and 2014 and conducted a prospective cohort study of kidney, heart, lung, pancreas and liver transplant recipients enrolled into the STCS by retrospective analysis of collected data. The STCS provided data on 2758 solid organ transplants.

Forty years of cisplatin-based chemotherapy in muscle-invasive bladder cancer: are we understanding how, who and when?

Purpose: For 40 years cisplatin-based chemotherapy has been administered to patients with muscle-invasive bladder cancer (MIBC). The best evidence of its efficacy is found in the context of neoadjuvant chemotherapy (NAC). However, the benefit to the patient is modest, with an improvement in 5-year overall survival of only 5-8%.

Pattern of Care Study in Metastatic Renal-Cell Carcinoma in the Preimmunotherapy Era in Switzerland.

Introduction: In metastatic renal-cell carcinoma (mRCC), physicians have a plethora of therapeutic choices, with the latest addition of checkpoint inhibitors. However, many questions regarding the best use of the respective drugs remain unanswered. Therefore, it is important to examine and summarize the outcome of real-world experiences to understand the practical value of the various drugs in daily use and foster optimal treatment algorithms for patients with renal-cell carcinoma.

Response to first-line treatment and histology are associated with achieving complete remission after the first salvage high-dose chemotherapy in relapsing germ cell tumor patients.

Sequential high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is a curative option in relapsing germ cell tumor (GCT) patients, and complete remission (CR) after the first ASCT (early CR2) is associated with favorable outcome. Prognostic factors predicting early CR2 have not been investigated so far. We analyzed consecutive patients with a first relapse of GCT treated with three sequential cycles of carboplatin/etoposide-based HDCT with ASCT in the two largest academic centers in Switzerland.

Functional interplay of SP family members and nuclear factor Y is essential for transcriptional activation of the human Calreticulin gene.

Calreticulin (CALR) is a highly conserved, multifunctional protein involved in a variety of cellular processes including the maintenance of intracellular calcium homeostasis, proper protein folding, differentiation and immunogenic cell death. More recently, a crucial role for CALR in the pathogenesis of certain hematologic malignancies was discovered: in clinical subgroups of acute myeloid leukemia, CALR overexpression mediates a block in differentiation, while somatic mutations have been found in the majority of patients with myeloproliferative neoplasms with nonmutated Janus kinase 2 gene (JAK2) or thrombopoietin receptor gene (MPL). However, the mechanisms underlying CALR promoter activation have insufficiently been investigated so far.

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML.

Deregulation of the myeloid key transcription factor CEBPA is a common event in acute myeloid leukemia (AML). We previously reported that the chaperone calreticulin is activated in subgroups of AML patients and that calreticulin binds to the stem loop region of the CEBPA mRNA, thereby blocking CEBPA translation. In this study, we screened for additional CEBPA mRNA binding proteins and we identified protein disulfide isomerase (PDI), an endoplasmic reticulum (ER) resident protein, to bind to the CEBPA mRNA stem loop region.

Activation of the unfolded protein response in human acute myeloid leukemia.

There is accumulating evidence for the involvement of the unfolded protein response (UPR) in the pathogenesis of many tumor types in humans. This is particularly the case in rapidly growing solid tumors in which the demand for oxygen and nutrients can exceed the supply until new tumor-initiated blood vessels are formed. In contrast, the role of the UPR during leukemogenesis remains largely unknown.

Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5.

Tissue transglutaminase (TG2) is implicated in cellular processes such as apoptosis and cell migration. Its acyl transferase activity cross-links certain proteins, among them transcription factors were described. We show here that the TG2 inhibitor KCC009 reversed resistance to tumor necrosis factor-related apoptosis-inducing factor (TRAIL) in lung cancer cells.

Complexity of miR-223 regulation by CEBPA in human AML.

microRNA-223 (miR-223) can trigger normal granulopoiesis. miR-223 expression is regulated by two distinct CEBPA (CCAAT/enhancer binding protein-alpha) sites. Here, we report that miR-223 is largely suppressed in cells from acute myeloid leukemia (AML) patients.

Unfolded protein response suppresses CEBPA by induction of calreticulin in acute myeloid leukaemia.

The unfolded protein response (UPR) is triggered by the accumulation of misfolded proteins within the endoplasmic reticulum (ER). The role of the UPR during leukemogenesis is unknown so far. Here, we studied the induction of mediators of the UPR in leukaemic cells of AML patients.

Activation of the unfolded protein response is associated with favorable prognosis in acute myeloid leukemia.

Purpose: The unfolded protein response is triggered by the accumulation of misfolded proteins within the endoplasmic reticulum. Previous studies suggest that the unfolded protein response is activated in some cancer cell lines and involved in tumor development. The role of the unfolded protein response during leukemogenesis is unknown thus far.

Somatic CEBPA mutations are a frequent second event in families with germline CEBPA mutations and familial acute myeloid leukemia.

Purpose: The transcription factor CCAAT/enhancer binding protein-alpha (CEBPA) is crucial for normal myeloid differentiation. Mutations in the CEBPA gene are found in subsets of patients with acute myeloid leukemia (AML). Recently, three families were reported in whom several family members had germline CEBPA mutations and subsequently developed AML.

Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer.

Chromosomal instability in human breast cancer is known to take place before mammary neoplasias display morphological signs of invasion. We describe here the unexpected finding of a tumor cell population with normal karyotypes isolated from bone marrow of breast cancer patients. By analyzing the same single cells for chromosomal aberrations, subchromosomal allelic losses, and gene amplifications, we confirmed their malignant origin and delineated the sequence of genomic events during breast cancer progression.

CBFB-SMMHC is correlated with increased calreticulin expression and suppresses the granulocytic differentiation factor CEBPA in AML with inv(16).

The pericentric inversion of chromosome 16, inv(16)(p13q22), is associated with acute myeloid leukemia (AML) subtype M4Eo that is characterized by the presence of myelomonocytic blasts and atypical eosinophils. This rearrangement fuses the CBFB and MYH11 genes, with the latter encoding the smooth muscle myosin heavy chain (SMMHC). The myeloid transcription factor CCAAT/enhancer-binding protein alpha (CEBPA) is crucial for normal granulopoiesis.

SCOMP is superior to degenerated oligonucleotide primed-polymerase chain reaction for global amplification of minute amounts of DNA from microdissected archival tissue samples.

Global genome amplification from formalin-fixed tissues is still problematic when performed with low cell numbers. Here, we tested a recently developed method for whole genome amplification termed "SCOMP" (single cell comparative genomic hybridization) on archival tissues of different ages. We show that the method is very well suited for formalin-fixed paraffin-embedded samples obtained by nuclei extraction or laser microdissection.