Oncology

Multivariable time-dependent analysis of the impact of azacitidine in patients with lower-risk myelodysplastic syndrome and unfavorable specific lower-risk score
Scoring systems for Lower-risk myelodysplastic syndrome (LR-MDS) recognize patients with a poorer than expected outcome. This study retrospectively analyzes the role of azacitidine in LR-MDS with adverse risk score and compared to an historical cohort treated with best supportive care or erythropoiesis-stimulating agents. Overall-response to AZA was 40%. One and 2-year probabilities of survival...


Diet-induced obesity promotes a myeloma-like condition in vivo
Multiple myeloma remains a fatal haematological malignancy associated with clonal plasma cell expansion within the bone marrow, osteolytic bone disease, anaemia and renal failure. In almost all cases, myeloma is preceded by the nonmalignant plasma cell disorder monoclonal gammopathy of undetermined significance (MGUS), characterized by an increase in monoclonal immunoglobulin secretion, <1...
Anti-tumor activities of selective HSP90α/β inhibitor, TAS-116, in combination with bortezomib in multiple myeloma
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that interacts with various client proteins in eukaryotic cells:1 Akt (PI3K/Akt pathway), interleukin-6 R (JAK/STAT pathway), Bcr-Abl (RAS/ERK pathway), Cyclin-dependent kinase 4, 6, 9 (cell cycling) and IκB kinases (NF-κB pathway).2 The expression of HSP90 is upregulated (2- t...


A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations
AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistically with histone deacetylase inhibitors (HDACIs, for example, Vorinostat), which interrupt the DNA damage response, to kill p53-wild type (wt) or -deficient as well as FLT3-ITD leukemia cells in a...
Elevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment
Elevated neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to be a poor prognostic factor in multiple types of malignancies, whereas the effect of NLR on the prognosis of epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) is not fully addressed. 81 metastatic NSCLC patients ...


Impact of the early detection of esophageal neoplasms in hypopharyngeal cancer patients treated with concurrent chemoradiotherapy
We examined the risk factors and prognostic factors for synchronous esophageal neoplasia (SEN) by comparing the characteristics of hypopharyngeal cancer (HPC) patients with and without SEN. We examined 183 patients who were treated with definitive radiotherapy for HPC. Lugol chromoendoscopy screening of the esophagus was performed in all patients before chemoradiotherapy. Thirty-six patients ha...
Interleukin-6 gene-174 G/C promoter polymorphism and its association with clinical profile of patients with multiple myeloma
In multiple myeloma (MM), the growth and survival of myeloma cells is controlled by interleukin-6 (IL-6), the plasma levels of which is controlled by a guanine/cytosine substitution occurring in position -174 of IL-6 gene promoter region. We studied the occurrence of IL-6-174 G/C polymorphism in patients of MM and correlated the presence of genotypes with serum IL-6 levels and tumor staging. On...

Notch Signaling Drives Stemness in Esophageal Adenocarcinoma
Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating g...
Cerk Promotes Tumor Recurrence
Recurrent breast cancer is typically an incurable disease and, as such, is disproportionately responsible for deaths from this disease. Recurrent breast cancers arise from the pool of disseminated tumor cells (DTC) that survive adjuvant or neoadjuvant therapy, and patients with detectable DTCs following therapy are at substantially increased risk for recurrence. Consequently, the identification...

Holo-RBP and STRA6 Are Oncogenes
Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP). At some tissues, RBP is recognized by STRA6, a plasma membrane protein that serves a dual role: it transports retinol from extracellular RBP into cells and it transduces a signaling cascade mediated by the Janus kinase JAK2 and the transcription factors STAT3 and STAT5. We show here that expression of RBP and STRA6 ...
SNAIL1 Is Required and Sufficient for Metastasis
SNAIL1 has been suggested to regulate breast cancer metastasis based on analyses of human breast tumor transcriptomes and experiments using cancer cell lines and xenografts. However, in vivo genetic experimental support for a role for SNAIL1 in breast cancer metastasis that develops in an immunocompetent tumor microenvironment has not been determined. To address this question, we created a gene...

SERPINB3 Induces Tumorigenesis via UPR and IL6 Signaling
The serine/cysteine protease inhibitor SCCA1 (SERPINB3) is upregulated in many advanced cancers with poor prognosis, but there is limited information about whether it makes functional contributions to malignancy. Here, we show that SCCA1 expression promoted oncogenic transformation and epithelial–mesenchymal transition (EMT) in mammary epithelial cells, and that SCCA1 silencing in breast canc...
PAD2 Overexpression Promotes Skin Neoplasia
Peptidylarginine deiminase 2 (PAD2/PADI2) has been implicated in various inflammatory diseases and, more recently, cancer. The goal of this study was to test the hypothesis that PAD2 promotes oncogenesis using a transgenic mouse model. We found that about 37% of transgenic mice overexpressing human FLAG-PAD2 downstream of the MMTV-LTR promoter develop spontaneous neoplastic skin lesions. Molecu...
ROSlow Cells with CIC Property and Chemoresistance
Head and neck squamous cell carcinoma (HNSCC) is driven by cancer-initiating cells (CIC), but their maintenance mechanisms are obscure. For hematopoietic stem cells, low levels of intracellular reactive oxygen species (ROSLow) is known to help sustain stemness properties. In this report, we evaluated the hypothesis that ROSLow character conferred CIC properties in HNSCC. Sphere cultures define ...
Dicer-Regulated miR326 Enhances ESCC Progression
Esophageal cancer is an aggressive human malignancy with increasing incidence in the developed world. VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here, we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CN), a regulator of the cortical actin cytoskeleton. Upregulation of C...