Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis

Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth

DataSheet_1_Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.docx

Bacillus Calmette–Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment. Programmed death-ligand 1, human epidermal growth factor receptor-2 (HER2), programmed cell death-1 (PD1), CD8, and Ki67 levels were measured in treatment-naïve NMIBC and MIBC patients (pTa, pT1, and pT2 stages). Univariate and multivariate Cox proportional hazard models were used to determine the impact of these markers and other clinicopathological factors on survival, recurrence, and progression. EP263, IM142, PD1, and Ki67 levels were the highest in the T2 stage, followed by the T1 and Ta stages. HER2 and IM263 expressions were higher in the T1 and T2 stages than in the Ta stage. In NMIBC, the significant prognostic factors for recurrence-free survival were adjuvant therapy, tumor grade, and HER2 positivity, whereas those for progression-free survival included age, T-stage, and IM263. Age, T-stage, EP263, PD1, CD8, and Ki67 levels were significant factors associated with overall survival. IM263 and HER2 are potential biomarkers for progression and recurrence, respectively. Therefore, we propose HER2 as a potential target antigen for intravesical therapeutics as a BCG alternative.</p

Figure S5 from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Gene expression in PDGF-BB stimulated fibroblasts</p

Supplementary Information from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Supplementary Figure Legends</p

Figure S2 from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Mouse CAFs promote breast cancer metastasis</p

Figure S4 from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Growth factor-stimulated fibroblasts promote NSCLC metastasis</p

Figure S1 from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Human CRC tumor fibrosis and isolation of CAFs</p

Dissemination of CAF-cancer cell complex from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Video - Dissemination of CAF-cancer cell complex</p

Figure S3 from A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Mouse CAFs promote CRC metastasis</p

Structure–Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells

Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor <b>2</b>. Initial structure–activity relationship studies resulted in compound <b>27</b> with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors <b>53</b> and <b>54</b>, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented