Delivering a RAS protease halts tumor growth.
Authors: Vidimar V, Melnyk RA, Satchell KJF PMID: 32934771 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Targeting 14-3-3 ε-CDC25A interactions to trigger apoptotic cell death in skin cancer.
Targeting 14-3-3ε-CDC25A interactions to trigger apoptotic cell death in skin cancer. Oncotarget. 2020 Sep 01;11(35):3267-3278 Authors: Holmes TR, Al-Matouq J, Holmes M, Nicola L, Rudd JC, Lovas S, Hansen LA Abstract Non-melanoma skin cancer is the most common form of cancer worldwide. We previously documented an anti-apoptotic role for CDC25A in cutaneous squamous cell carcinoma (SCC), an activity dependent on its association with 14-3-3 proteins. We hypothesized that targeting CDC25A-14-3-3ε interactions may be an effective strategy for inducing skin cancer cell apoptosis. Co-immunopr...
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Sequencing for an interdisciplinary molecular tumor board in patients with advanced breast cancer: experiences from a case series.
CONCLUSIONS: Using a high throughput-panel sequencing approach to identify actionable mutations in patients with metastatic breast cancer, we identified potential target-related treatment options in a large proportion of our patients, some of which would not have been considered without this data. Prospective clinical trials with compounds targeting the identified actionable mutations are needed to determine which treatments can indeed improve survival or quality of life by limiting exposure to ineffective drugs in advanced breast cancer. PMID: 32934773 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Ghrelin ameliorates tumor-induced adipose tissue atrophy and inflammation via Ghrelin receptor-dependent and -independent pathways.
In conclusion, ghrelin ameliorates WAT inflammation, fat atrophy and anorexia in LLC-induced cachexia. GHSR-1a is required for ghrelin's orexigenic effect but not for its anti-inflammatory or fat-sparing effects. PMID: 32934774 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The temporal effects of topical NF- κB inhibition, in the in vivo prevention of bile-related oncogenic mRNA and miRNA phenotypes in murine hypopharyngeal mucosa: a preclinical model.
The temporal effects of topical NF-κB inhibition, in the in vivo prevention of bile-related oncogenic mRNA and miRNA phenotypes in murine hypopharyngeal mucosa: a preclinical model. Oncotarget. 2020 Sep 01;11(35):3303-3314 Authors: Vageli DP, Kasle D, Doukas SG, Doukas PG, Sasaki CT Abstract Supraesophageal bile reflux at strongly acidic pH can cause hypopharyngeal squamous cell cancer, through activation of the oncogenic NF-κB-related pathway. We hypothesize that topical pre- or post-application of pharmacologic NF-κB inhibitor, BAY 11-7082 (0.25 μmol), on murine (C57BL/6J) HM (tw...
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers.
Authors: Balhorn R, Balhorn MC Abstract SH7139, the first of a series of selective high affinity ligand (SHAL) oncology drug candidates designed to target and bind to the HLA-DR proteins overexpressed by B-cell lymphomas, has demonstrated exceptional efficacy in the treatment of Burkitt lymphoma xenografts in mice and a safety profile that may prove to be unprecedented for an oncology drug. The aim of this study was to determine how frequently the HLA-DRs targeted by SH7139 are expressed by different subtypes of non-Hodgkin's lymphoma and by other solid cancers that have been reported to express HLA-DR. Binding stu...
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways.
Authors: Yang J, Pei H, Luo H, Fu A, Yang H, Hu J, Zhao C, Chai L, Chen X, Shao X, Wang C, Wu W, Wan L, Ye H, Qiu Q, Peng A, Wei Y, Yang L, Chen L Abstract [This corrects the article DOI: 10.18632/oncotarget.13687.]. PMID: 32934777 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Diversifying the platinum-based chemotherapy toolkit for immunogenic cancer cell death.
Authors: Garg AD, Agostinis P PMID: 32934778 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma and APOBEC3B is directly transcriptionally regulated by GATA3.
Authors: Gara SK, Tyagi MV, Patel DT, Gaskins K, Lack J, Liu Y, Kebebew E Abstract Recent evidence has implicated APOBEC3B (Apolipoprotein B mRNA editing enzyme catalytic subunit 3B) as a source of mutations in breast, bladder, cervical, lung, head, and neck cancers. However, the role of APOBEC3B in adrenocortical carcinoma (ACC) and the mechanisms through which its expression is regulated in cancer are not fully understood. Here, we report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. We show high APOBEC3B expression is associated with a higher copy number ga...
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Targeted CRM1-inhibition perturbs leukemogenic NUP214 fusion proteins and exerts anti-cancer effects in leukemia cell lines with NUP214 rearrangements.
In this report, we show that SET-NUP214 and DEK-NUP214 both disturb the localization of proteins essential for nucleocytoplasmic transport, in particular for CRM1-mediated protein export. Endogenous and exogenous SET-NUP214 and DEK-NUP214 form nuclear bodies. These nuclear bodies disperse upon targeted inhibition of CRM1 and the two fusion proteins re-localize throughout the nucleoplasm. Moreover, SET-NUP214 and DEK-NUP214 nuclear bodies reestablish shortly after removal of CRM1 inhibitors. Likewise, cell viability, metabolism, and proliferation of leukemia cell lines harboring SET-NUP214 and DEK-NUP214 are compromised by ...
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Down syndrome iPSC model: endothelial perspective on tumor development.
Authors: Perepitchka M, Galat Y, Beletsky IP, Iannaccone PM, Galat V Abstract Trisomy 21 (T21), known as Down syndrome (DS), is a widely studied chromosomal abnormality. Previous studies have shown that DS individuals have a unique cancer profile. While exhibiting low solid tumor prevalence, DS patients are at risk for hematologic cancers, such as acute megakaryocytic leukemia and acute lymphoblastic leukemia. We speculated that endothelial cells are active players in this clinical background. To this end, we hypothesized that impaired DS endothelial development and functionality, impacted by genome-wide T21 altera...
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Association of functional IL16 polymorphisms with cancer and cardiovascular disease: a meta-analysis.
CONCLUSIONS: Our meta-analysis suggested that the SNPs rs11556218 and rs4778889 of IL16 were associated with an increased risk for cancer in Chinese and rs11556218 with increased risk for CVD in Chinese, highlighting the need for further studies on the impact of these polymorphisms on cancer treatment and surveillance. PMID: 32934782 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 18, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Paradox breaker BRAF inhibitors have comparable potency and MAPK pathway reactivation to encorafenib in BRAF mutant colorectal cancer.
Authors: Pickles OJ, Drozd A, Tee L, Beggs AD, Middleton GW Abstract The BEACON CRC trial demonstrated a survival advantage over chemotherapy for a combination of targeted agents comprising the potent BRAF inhibitor encorafenib together with cetuximab and binimetinib. Resistance to BRAF inhibition in CRC arises in part through the generation and activation of RAF dimers resulting in MEK-ERK pathway reactivation. Paradox breaker BRAF inhibitors, such as PLX8394, are designed to inhibit RAF dimer formation. We analyzed whether paradox breakers reduce pathway reactivation and so have enhanced potency compared with enc...
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Detection of circulating tumor DNA in patients of operative colorectal and gastric cancers.
Authors: Suzuki T, Suzuki T, Yoshimura Y, Yahata M, Yew PY, Nakamura T, Nakamura Y, Park JH, Matsuo R Abstract Liquid biopsy is a non-invasive tool to examine the genetic profile of tumors by identification of mutated circulating tumor DNA (ctDNA), which is often analyzed by next generation sequencing (NGS) or droplet digital PCR (ddPCR) assay. We first examined the ctDNA mutation in pre-operative plasma samples obtained from 154 colorectal cancer (CRC) and 46 gastric cancer (GC) patients, using the NGS-based panel assay. The overall detection rate of mutated ctDNA was 72.0% (144 of 200 patients), and the panel-bas...
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL).
Authors: Nagel S, Pommerenke C, MacLeod RAF, Meyer C, Kaufmann M, Drexler HG Abstract NKL homeobox genes encode developmental transcription factors and display an NKL-code according to their physiological expression pattern in hematopoiesis. Here, we analyzed public transcriptome data from primary innate lymphoid cells (ILCs) for NKL homeobox gene activities and found that ILC3 expressed exclusively HHEX while in ILC1 and ILC2 these genes were silenced. Deregulation of the NKL-code promotes hematopoietic malignancies, including anaplastic large cell lymphoma (ALCL) which reportedly may derive from ILC3. Accordingly...
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Differentially expressed full-length, fusion and novel isoforms transcripts-based signature of well-differentiated keratinized oral squamous cell carcinoma.
Authors: Singh N, Sahu DK, Tripathi RK, Mishra A, Shyam H, Shankar P, Jain M, Alam N, Kumar A, Mishra A, Chowdhry R, Singh A, Gupta S, Mehrotra D, Agarwal P, Goel MM, Chaturvedi A, Agarwal SP, Bajpai M, Gupta DK, Bhatt MLB, Kant R Abstract Highly keratinized oral squamous cell carcinoma (OSCC) exhibits an improved response to treatment and prognosis compared with weakly keratinized OSCC. Therefore, we aimed to develop gene transcript signature and to identify novel full-length isoforms, fusion transcript and non-coding RNA to differentiate well-differentiated (WD) with Moderately Differentiated (MD)/Poorly Differen...
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Urinary glycoproteomic profiling of non-muscle invasive and muscle invasive bladder carcinoma patients reveals distinct N-glycosylation pattern of CD44, MGAM, and GINM1.
In this study, we investigated the aberrant changes in N-glycosylation pattern of proteins associated with tumorigenesis as well as disease progression in bladder cancer. We integrated and compared global N-glycoproteomic and proteomic profile of urine samples from bladder cancer patients at different clinicopathological stages (non-muscle invasive and muscle-invasive patients [n = 5 and 4 in each cohort]) with healthy subjects (n = 5) using SPEG method. We identified 635 N-glycopeptides corresponding to 381 proteins and 543 N-glycopeptides corresponding to 326 proteins in NMIBC and MIBC patients respectively. Moreover, we...
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A case report of metastatic giant sarcomatoid melanoma with BRAF V600E mutation: a complete response to targeted therapy.
Authors: Torresetti M, Brancorsini D, Morgese F, Cognigni V, Scalise A, Berardi R, Di Benedetto G Abstract Sarcomatoid melanoma is an extremely rare pattern of malignant melanoma, and only few cases have been described throughout the literature. We herein report a case of a patient with newly diagnosed, metastatic giant sarcomatoid melanoma of the arm. The patient underwent surgical removal of the huge mass, and NGS sequencing demonstrated BRAF V600E mutation. In view of histological, immunohistochemical and molecular findings, a combined BRAF/MEK inhibitor (BRAF/MEK-i) therapy was prescribed as first line treatmen...
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: MicroRNA-21 promotes TGF- β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression.
Correction: MicroRNA-21 promotes TGF-β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression. Oncotarget. 2020 Aug 25;11(34):3263-3264 Authors: Li C, Song L, Zhang Z, Bai XX, Cui MF, Ma LJ Abstract [This corrects the article DOI: 10.18632/oncotarget.11888.]. PMID: 32922665 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 16, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A multicenter, single-arm, basket design, phase II study of NC-6004 plus gemcitabine in patients with advanced unresectable lung, biliary tract, or bladder cancer.
Authors: Volovat SR, Ciuleanu TE, Koralewski P, Olson JEG, Croitoru A, Koynov K, Stabile S, Cerea G, Osada A, Bobe I, Volovat C Abstract NC-6004 is a nanoparticle developed using micellar technology that can improve release of cisplatin, a standard treatment for many cancer types, and achieve selective distribution to tumors. Here, in the Phase II portion of this study, the activity, safety, tolerability, and effects on quality of life of NC-6004 in combination with gemcitabine was examined in 34 squamous non-small cell lung carcinoma (NSCLC) patients, 50 biliary tract cancer patients, and 13 bladder cancer patient...
Source: Oncotarget - September 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases.
CONCLUSIONS: Our findings suggest a unique molecular profile for MBM, including higher rates of BRAF mutations, higher TMB and higher PD-L1 expression, and also implicate chromatin remodeling in the pathogenesis of MBM. PMID: 32913556 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Carnosic acid increases sorafenib-induced inhibition of ERK1/2 and STAT3 signaling which contributes to reduced cell proliferation and survival of hepatocellular carcinoma cells.
Authors: Wang X, Gupta P, Jramne Y, Danilenko M, Liu D, Studzinski GP Abstract Hepatocellular carcinoma (HCC) has increasing worldwide incidence but when unresectable lacks curative options. Treatment with a kinase inhibitor Sorafenib (Sf), while initially effective, results in only short increases in patient survival, thus there is a need for improved treatment regimens. Numerous treatment regimens have been explored wherein Sf is combined with other agents, such as non-toxic botanicals like Curcumin or Silibinin. Recently, we have shown that carnosic acid (CA), a component of the food preservative Rosemary Extrac...
Source: Oncotarget - September 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Superior prognosis stratification for stage III colon cancer using log odds of positive lymph nodes (LODDS) compared to TNM stage classification: the Japanese study group for postoperative follow-up of colorectal cancer.
Authors: Ogawa S, Itabashi M, Bamba Y, Yamamoto M, Sugihara K Abstract OBJECTIVES: The aim of this study is to examine whether prognosis stratification in staging of Stage III colon cancer using T factor and log odds of positive lymph nodes (LODDS) categories is superior to that of the TNM staging system. MATERIALS AND METHODS: The subjects were 5,919 patients with Stage III colon cancer who underwent curative resection at 24 Japanese institutions. Univariate analysis of LODDS categories and clinicopathologic factors was conducted using a Cox proportional hazards regression model for cancer-specific survival (C...
Source: Oncotarget - September 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

An integrative microenvironment approach for follicular lymphoma: roles of inflammatory cell subsets and immune-response polymorphisms on disease clinical course.
Authors: Assis-Mendonça GR, Fattori A, Rocha RM, Lourenço GJ, Delamain MT, Nonogaki S, de Lima VCC, Colleoni GWB, de Souza CA, Soares FA, Lima CSP, Vassallo J Abstract The study of the tumor microenvironment (TME) in follicular lymphoma (FL) has produced conflicting results due to assessment of limited TME subpopulations, and because of heterogeneous treatments among different cohorts. Also, important genetic determinants of immune response, such as single-nucleotide polymorphisms (SNPs), remain underexplored in this disease. We performed a detailed study of the TME in 169 FL biopsies using immunohist...
Source: Oncotarget - September 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The bromodomain inhibitor IBET-151 attenuates vismodegib-resistant esophageal adenocarcinoma growth through reduction of GLI signaling.
Authors: Alvarez-Trotta A, Wang Z, Shersher E, Li B, Long J, Lohse I, Wahlestedt C, El-Rifai W, Robbins DJ, Capobianco AJ Abstract The Hedgehog/GLI (HH/GLI) signaling pathway plays a critical role in human oncogenesis. Unfortunately, the clinical use of HH inhibitor(s) has been associated with serious adverse effects and mutation-related drug resistance. Since the efficacy of SMO (Smoothened) and GLI inhibitors is limited in clinical trials, there remains a critical need for the HH/GLI pathway inhibitors with different mechanisms of action. Here, we show that esophageal adenocarcinoma (EAC) cell lines are insensiti...
Source: Oncotarget - September 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Survival after resection of brain metastases with white light microscopy versus fluorescence-guidance: A matched cohort analysis of the Metastasys study data.
CONCLUSIONS: The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy. The most prominent predictors of survival remain favorable preoperative performance status, a low tumor diameter and the absence of multiple cerebral lesions. PMID: 32850007 [PubMed] (Source: Oncotarget)
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Obinutuzumab (GA101) vs. rituximab significantly enhances cell death, antibody-dependent cytotoxicity and improves overall survival against CD20+ primary mediastinal B-cell lymphoma (PMBL) in a xenograft NOD-scid IL2Rgnull (NSG) mouse model: a potential targeted agent in the treatment of PMBL.
Authors: Chu Y, Awasthi A, Lee S, Edani D, Yin C, Hochberg J, Shah T, Chung TH, Ayello J, van de Ven C, Klein C, Lee D, Cairo MS Abstract Primary mediastinal large B-cell lymphoma (PMBL), a distinct mature B-cell lymphoma, expresses CD20 and has recently been successfully treated with the combination of a type I anti-CD20 monoclonal antibody, rituximab, with multiple combination chemotherapy regimens. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody (mAb), recognizing a unique CD20 extracellular membrane epitope with enhanced antibody dependent cellular cytotoxicity (ADCC) vs rituximab. We hy...
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models.
Authors: Mainetti LE, Rico MJ, Kaufman CD, Grillo MC, Guercetti J, Baglioni MV, Del Giúdice A, Capitani MC, Fusini M, Rozados VR, Scharovsky OG Abstract Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology the combination of these two therapeutic approaches is called "Metronomics". The aim of this work is to evaluate the therapeutic effect of cyclophosphami...
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Post FDA approval analysis of 200 gallium-68 DOTATATE imaging: A retrospective analysis in neuroendocrine tumor patients.
Authors: Chauhan A, El-Khouli R, Waits T, Agrawal R, Siddiqui F, Tarter Z, Horn M, Weiss H, Oates E, Evers BM, Anthony L Abstract Gallium-68 DOTATATE provides physiologic imaging and assists in disease localization for somatostatin receptor (SSTR) positive neuroendocrine tumor (NET) patients. However, questions regarding usefulness of gallium- 68 DOTATATE imaging in identifying the primary site in neuroendocrine tumors (NETS) of unknown primary, correlation of NET grade with median Standardized Uptake Value (SUV) and effects of long acting somatostatin analog on gallium-68 DOTATATE imaging quality needs to be evalu...
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Preclinical evaluation of the anti-tumor activity of pralatrexate in high-risk neuroblastoma cells.
CONCLUSIONS: Pralatrexate demonstrated effective inhibition of cell growth and viability. The higher potency of pralatrexate compared to methotrexate, a drug with high levels of toxicity, suggests pralatrexate may be a safer alternative to methotrexate as an effective chemotherapeutic agent in the treatment of patients with high-risk neuroblastoma. PMID: 32850011 [PubMed] (Source: Oncotarget)
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Important players in carcinogenesis as potential targets in cancer therapy: an update.
Authors: Hermanowicz JM, Kwiatkowska I, Pawlak D Abstract The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome proliferator-activated receptors (PPAR), fatty acid-binding prot...
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: LRP6 promotes invasion and metastasis of colorectal cancer through cytoskeleton dynamics.
Authors: Yao Q, An Y, Hou W, Cao YN, Yao MF, Ma NN, Hou L, Zhang H, Liu HJ, Zhang B Abstract [This corrects the article DOI: 10.18632/oncotarget.22759.]. PMID: 32850013 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells.
Authors: Kakar SS, Parte S, Carter K, Joshua IG, Worth C, Rameshwar P, Ratajczak MZ Abstract [This corrects the article DOI: 10.18632/oncotarget.20170.]. PMID: 32850014 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - August 29, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Thymoquinone induces apoptosis and DNA damage in 5-Fluorouracil-resistant colorectal cancer stem/progenitor cells.
Authors: Ballout F, Monzer A, Fatfat M, Ouweini HE, Jaffa MA, Abdel-Samad R, Darwiche N, Abou-Kheir W, Gali-Muhtasib H Abstract The high recurrence rates of colorectal cancer have been associated with a small population of cancer stem cells (CSCs) that are resistant to the standard chemotherapeutic drug, 5-fluorouracil (5FU). Thymoquinone (TQ) has shown promising antitumor properties on numerous cancer systems both in vitro and in vivo; however, its effect on colorectal CSCs is poorly established. Here, we investigated TQ's potential to target CSCs in a three-dimensional (3D) sphere-formation assay enriched for a p...
Source: Oncotarget - August 23, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Sirolimus-eluting stents: opposite in vitro effects on the clonogenic cell potential on a long-term exposure.
In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types. In the practice, the plaque typology and composition may influence the response to sirolimus and thus the effectiveness of eluted stent. PMID: 32821343 [PubMed - as supplied by publisher] (Source: Oncotarget)
Source: Oncotarget - August 23, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma.
In this study, we investigated the relationship between the presence of diabetes mellitus (blood hemoglobin A1C was 6.5% or higher at the time of diagnosis of CRC) and the progression and liver metastasis of CRC. Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC (DM-CRC) and the liver metastasis, were also investigated. Of the 473 CRC patients who underwent curative surgical resection, 148 (31%) had diabetes. In DM-CRC cases, the stage was more advanced, with more cases in stage IV or postoperative disease recurrence. Histopathological findings correlated with liver meta...
Source: Oncotarget - August 23, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers.
CONCLUSIONS: In this study, we demonstrate utilization of circulating ESFT-associated sEVs in pediatric patients as a source of minimally invasive diagnostic and potentially prognostic biomarkers. PMID: 32821345 [PubMed - as supplied by publisher] (Source: Oncotarget)
Source: Oncotarget - August 23, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Mitochondrial uncoupling and the disruption of the metabolic network in hepatocellular carcinoma.
CONCLUSIONS: FH535, and Y3, demonstrated potent anti-HCC activity by targeting OXPHOS, increasing dangerous levels of ROS and reducing ATP production. These sulfonamides target glutamine and FA metabolic pathways significantly increasing the cellular dependency on glycolysis. PMID: 32821346 [PubMed - as supplied by publisher] (Source: Oncotarget)
Source: Oncotarget - August 23, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5.
Authors: Al-Jameel W, Gou X, Forootan SS, Fayi MSA, Rudland PS, Forootan FS, Zhang J, Cornford PA, Hussain SA, Ke Y Abstract [This corrects the article DOI: 10.18632/oncotarget.16055.]. PMID: 32821347 [PubMed - as supplied by publisher] (Source: Oncotarget)
Source: Oncotarget - August 23, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Genomic markers of midostaurin drug sensitivity in FLT3 mutated and FLT3 wild-type acute myeloid leukemia patients.
Authors: Rosenberg MW, Watanabe-Smith K, Tyner JW, Tognon CE, Druker BJ, Borate U Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy with the most common genomic alterations in NPM1, DNMT3A, and FLT3. Midostaurin was the first FLT3 inhibitor FDA approved for AML and is standard of care for FLT3 mutant patients undergoing induction chemotherapy [1, 2]. As there is a spectrum of response, we hypothesized that biological factors beyond FLT3 could play a role in drug sensitivity and that select FLT3-ITD negative samples may also demonstrate sensitivity. Thus, we aimed to identify features that would pr...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2) in preclinical models of ovarian and uterine cancer.
Authors: Lara OD, Bayraktar E, Amero P, Ma S, Ivan C, Hu W, Wang Y, Mangala LS, Dutta P, Bhattacharya P, Ashizawa AT, Lopez-Berestein G, Rodriguez-Aguayo C, Sood AK Abstract BACKGROUND: Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in gynecologic cancer models. MATERIALS AND METHODS: Murine orthotopic models of ovarian (OVCAR5 and SKOV3ip1) and uterine (Hec1a) cancer were used to study the biological effe...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Geriatric nutritional risk index as a prognostic marker of pTNM-stage I and II esophageal squamous cell carcinoma after curative resection.
Authors: Hirahara N, Matsubara T, Fujii Y, Kaji S, Hyakudomi R, Yamamoto T, Uchida Y, Miyazaki Y, Ishitobi K, Kawabata Y, Tajima Y Abstract The geriatric nutritional risk index (GNRI) is associated with mortality in several malignancies. We retrospectively analyzed whether the GNRI can predict long-term outcomes in 191 patients with esophageal squamous cell carcinoma (ESCC) after curative esophagectomies by evaluating their cancer-specific survival (CSS). In multivariate analyses, serum albumin (hazard ratio [HR], 2.498; p = 0.0043), GNRI (HR, 1.941; p = 0.0181), pathological tumor-node-metastasis (pTNM) stage (HR, 3.884; p
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Exosomal lncRNA PCAT-1 promotes Kras-associated chemoresistance via immunosuppressive miR-182/miR-217 signaling and p27/CDK6 regulation.
In this study, we investigate the role of lncRNA PCAT-1 in chemoresistant immunosuppression and its involvement in tumor stroma remodeling. Findings reveal PCAT-1 to regulate Kras-related lung chemoresistance through increased expression of the immunosuppressive micrornas miR-182/miR217 in lung tissues, thus promoting a pre-metastatic niche formation and a subsequent increase in lung metastatic burden. Elevated expression of PCAT-1 negative regulates p27/CDK6 expression by inducing G0/G1 cell cycle arrest through AMPK augmentation, contributing to a tumor-promoting status. Furthermore, PCAT-1 triggered fibroblast different...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Baicalin inhibits the TGF- β1/p-Smad3 pathway to suppress epithelial-mesenchymal transition-induced metastasis in breast cancer.
Baicalin inhibits the TGF-β1/p-Smad3 pathway to suppress epithelial-mesenchymal transition-induced metastasis in breast cancer. Oncotarget. 2020 Jul 21;11(29):2863-2872 Authors: Liu DK, Dong HF, Liu RF, Xiao XL Abstract TGF-β1 is an epithelial-mesenchymal transition (EMT)-inducing factor that is critical in tumor progression. However, whether the effect of TGF-β1 on breast cancer is through the EMT pathway remains to be determined, and drug development based on this mechanism needs to be improved. Results of this study showed that TGF-β1 dysregulation significantly correlated with t...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Th1 cytokines in conjunction with pharmacological Akt inhibition potentiate apoptosis of breast cancer cells in vitro and suppress tumor growth in vivo.
Authors: Showalter L, Czerniecki BJ, Koski GK Abstract Targeted drug approaches have been a major focus for developing new anticancer therapies. Although many such agents approved in the last 20 years have improved outcomes, almost all have underperformed expectations. The full potential of such agents may yet be obtained through novel combinations. Previously, we showed that anti-estrogen drugs combined with a dendritic cell-based anti-HER-2 vaccine known to induce strong Th1-polarized immunity dramatically improved clinical response rates in patients with HER-2pos/ERpos early breast cancer. Here, we show that the...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibition of HAS2 and hyaluronic acid production by 1,25-Dihydroxyvitamin D3 in breast cancer.
Authors: Narvaez CJ, LaPorta E, Robilotto S, Liang J, Welsh J Abstract 1,25-Dihydroxyvitamin D3 (1,25D3) induces growth arrest and apoptosis in breast cancer cells in vivo and in vitro, however the exact mechanisms are unclear. Although the vitamin D receptor (VDR), a ligand dependent transcription factor, is required for growth regulation by vitamin D, the specific target genes that trigger these effects are unknown. Genomic profiling of murine mammary tumor cells with differential VDR expression identified 35 transcripts that were altered by the 1,25D3-VDR complex including Hyaluronan Synthase-2 (Has2). Here we c...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Biomarker analysis to predict the pathological response to neoadjuvant chemotherapy in locally advanced gastric cancer: An exploratory biomarker study of COMPASS, a randomized phase II trial.
CONCLUSIONS: The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis. PMID: 32774771 [PubMed] (Source: Oncotarget)
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro.
Authors: Frank-Kamenetskii A, Mook J, Reeves M, Boulanger CA, Meyer TJ, Ragle L, Jordan HC, Smith GH, Booth BW Abstract The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using in vivo and in vitro models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We ha...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

cGAS-STING pathway in oncogenesis and cancer therapeutics.
Authors: Hoong BYD, Gan YH, Liu H, Chen ES Abstract The host innate immunity offers the first line of defense against infection. However, recent evidence shows that the host innate immunity is also critical in sensing the presence of cytoplasmic DNA derived from genomic instability events, such as DNA damage and defective cell cycle progression. This is achieved through the cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon (IFN) genes (STING) pathway. Here we discuss recent insights into the regulation of this pathway in cancer immunosurveillance, and the downstream signaling cascades that coordinate immune c...
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: Involvement of p53/FoxO3A axis.
Authors: Nepal S, Kim MJ, Hong JT, Kim SH, Sohn DH, Lee SH, Song K, Choi DY, Lee ES, Park PH Abstract [This corrects the article DOI: 10.18632/oncotarget.3347.]. PMID: 32774774 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - August 13, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research