Selecting suitable chemotherapies for PD-1/PD-L1 blockade to optimize the tumor immune microenvironment.
Authors: Koyama S, Nagatomo I, Kijima T, Kumanogoh A PMID: 30220963 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Balance deficits in long-term pediatric ALL survivors.
Authors: Varedi M, Ness KK, McKenna RF PMID: 30220964 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Tumor cell density regulates matrix metalloproteinases for enhanced migration.
This study reveals that the expression of MMPs is tightly regulated by local tumor cell density through the synergistic signaling mechanism of Interleukin 6 (IL-6) and Interleukin 8 (IL-8) via the JAK2/STAT3 complex. Local tumor cell density also plays a role in the responsiveness of cells to matrix metalloproteinases inhibitors (MMPI), such as Batimastat, Marimastat, Bryostatin I, and Cipemastat, where different migratory phenotypes are observed in low and high cell density conditions. Cell density-dependent MMP regulation can be directly targeted by the simultaneous inhibition of IL-6 and IL-8 receptors via Tocilizumab a...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Circulating tumor DNA as a marker of treatment response in BRAF V600E mutated non-melanoma solid tumors.
Conclusion: BRAFi combination therapies showed a response rate of 50% in BRAF V600E-mutated non-melanoma tumors. The fraction of BRAF-mutant cfDNA represent a sensitive indicator for clinical outcomes with plasma collected at week 4 and 12 as crucial time points for monitoring response and disease progression. PMID: 30220966 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Chromatin remodeling protein HELLS is upregulated by inactivation of the RB-E2F pathway and is nonessential for osteosarcoma tumorigenesis.
In this study, we examined the transcription factor E2F family members that are associated with increased malignancy in Rb1-null osteosarcoma tumors. Using genetically engineered mouse models of osteosarcoma, we found that loss of activator E2Fs, E2F1 and E2F3, significantly delays tumor progression and increases the overall survival of the p53/Rb1-deficient osteosarcoma mouse model. We also studied the role of helicase, lymphoid specific (HELLS), a chromatin remodeling protein identified as a critical downstream effector of the RB-E2F signaling pathway in various cancers. In this study, we confirmed that the RB-E2F pathwa...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells.
Authors: Virtanen SS, Ishizu T, Sandholm JA, Löyttyniemi E, Väänänen HK, Tuomela JM, Härkönen PL Abstract Bisphosphonates are used for prevention of osteoporosis and metastatic bone diseases. Anti-invasive effects on various cancer cells have also been reported, but the mechanisms involved are not well-understood. We investigated the effects of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization and the dynamics of actin, and on the cytoskeleton-related regulatory proteins cofilin...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Hematopoietic lineage cell-specific protein 1 (HS1), a hidden player in migration, invasion, and tumor formation, is over-expressed in ovarian carcinoma cells.
Authors: Koya Y, Liu W, Yamakita Y, Senga T, Shibata K, Yamashita M, Nawa A, Kikkawa F, Kajiyama H Abstract Hematopoietic lineage cell-specific protein 1 (HS1), which is the hematopoietic homolog of cortactin, is an actin-binding protein and Lyn substrate. It is upregulated in several cancers and its expression level is associated with increased cell migration, metastasis, and poor prognosis. Here we investigated the expression and roles of HS1 in ovarian carcinoma cells. We analyzed the expression of HS1 in 171 ovarian cancer specimens and determined the association between HS1 expression and clinicopathological c...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Quantitative screening of serum protein biomarkers by reverse phase protein arrays.
Authors: Kuang Z, Huang R, Yang Z, Lv Z, Chen X, Xu F, Yi YH, Wu J, Huang RP Abstract Screening biomarkers in serum samples for different diseases has always been of great interest because it presents an early, reliable, and, most importantly, noninvasive means of diagnosis and prognosis. Reverse phase protein arrays (RPPAs) are a high-throughput platform that can measure single or limited sets of proteins from thousands of patients' samples in parallel. They have been widely used for detection of signaling molecules involved in diseases, especially cancers, and related regulation pathways in cell lysates. However,...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Mutational analysis of uterine cervical cancer that survived multiple rounds of radiotherapy.
Authors: Nuryadi E, Sasaki Y, Hagiwara Y, Permata TBM, Sato H, Komatsu S, Yoshimoto Y, Murata K, Ando K, Kubo N, Okonogi N, Takakusagi Y, Adachi A, Iwanaga M, Tsuchida K, Tamaki T, Noda SE, Hirota Y, Shibata A, Ohno T, Tokino T, Oike T, Nakano T Abstract Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencin...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The frequency of promoter DNA hypermethylation is decreased in colorectal neoplasms of familial adenomatous polyposis.
Authors: Takane K, Fukuyo M, Matsusaka K, Ota S, Rahmutulla B, Matsushita K, Miyauchi H, Nakatani Y, Matsubara H, Kaneda A Abstract Familial adenomatous polyposis (FAP) is an inherited disorder characterized by numerous colorectal adenomatous polyps with predisposition to the development of colorectal cancer (CRC). Here, we conducted genome-wide DNA methylation analysis of FAP neoplasms, including seven cancer samples and 16 adenoma samples, using an Infinium 450K BeadArray. As controls for sporadic colorectal neoplasms and mucosae, we used Infinium 450k data from 297 CRC samples, 45 colorectal adenoma samples, and...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Involvement of GLUT1-mediated glucose transport and metabolism in gefitinib resistance of non-small-cell lung cancer cells.
Authors: Suzuki S, Okada M, Takeda H, Kuramoto K, Sanomachi T, Togashi K, Seino S, Yamamoto M, Yoshioka T, Kitanaka C Abstract Use of epidermal growth factor receptor (EGFR) inhibitors represented by gefitinib and erlotinib has become the standard of treatment for non-small-cell lung cancers (NSCLCs) with activating EGFR mutations. However, the majority of NSCLCs, which overexpress EGFR without such mutations, are resistant to EGFR inhibitors, and the mechanism(s) behind such primary resistance of NSCLCs without activating EGFR mutations to EGFR inhibitors still remains poorly understood. Here in this study, we sho...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation.
Conclusion: RILA does not correlate with the inter-individual variation in MDT or MUT in the largest cohort of patients overexposed to radiation. The magnitude of the overdosage probably overrides biological predictors of toxicity, including individual radiosensitivity. PMID: 30220974 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A high-throughput fluorescence polarization assay for discovering inhibitors targeting the DNA-binding domain of signal transducer and activator of transcription 3 (STAT3).
Authors: Shih PC, Yang Y, Parkinson GN, Wilderspin A, Wells G Abstract Anti-cancer drug discovery efforts to directly inhibit the signal transducer and activator of transcription 3 (STAT3) have been active for over a decade following the discovery that 70% of cancers exhibit elevated STAT3 activity. The majority of research has focused on attenuating STAT3 activity through preventing homo-dimerization by targeting the SH2 or transcriptional activation domains. Such dimerization inhibitors have not yet reached the market. However, an alternative strategy focussed on preventing STAT3 DNA-binding through targeting the...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Dual targeting of HSP70 does not induce the heat shock response and synergistically reduces cell viability in muscle invasive bladder cancer.
Authors: Prince T, Ackerman A, Cavanaugh A, Schreiter B, Juengst B, Andolino C, Danella J, Chernin M, Williams H Abstract Muscle invasive bladder cancer (MIBC) is a common malignancy and major cause of morbidity worldwide. Over the last decade mortality rates for MIBC have not decreased as compared to other cancers indicating a need for novel strategies. The molecular chaperones HSP70 and HSP90 fold and maintain the 3-dimensional structures of numerous client proteins that signal for cancer cell growth and survival. Inhibition of HSP70 or HSP90 results in client protein degradation and associated oncogenic signalin...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A patient-derived orthotopic xenograft model enabling human high-grade urothelial cell carcinoma of the bladder tumor implantation, growth, angiogenesis, and metastasis.
Authors: Gills J, Moret R, Zhang X, Nelson J, Maresh G, Hellmers L, Canter D, Hudson M, Halat S, Matrana M, Marino MP, Reiser J, Shuh M, Laborde E, Latsis M, Talwar S, Bardot S, Li L Abstract High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic...
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR signaling pathway promotes breast cancer motility, invadopodia formation and metastasis in vivo.
Authors: Yang H, Guan L, Li S, Jiang Y, Xiong N, Li L, Wu C, Zeng H, Liu Y Abstract [This corrects the article DOI: 10.18632/oncotarget.7583.]. PMID: 30220978 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy.
Authors: Mellai M, Cattaneo M, Storaci AM, Annovazzi L, Cassoni P, Melcarne A, De Blasio P, Schiffer D, Biunno I Abstract [This corrects the article DOI: 10.18632/oncotarget.3611.]. PMID: 30220979 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Rituximab mechanisms of action in B-CLL: a new piece of the puzzle.
Authors: Watier H PMID: 30214679 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Acquired palbociclib resistance in KRAS-mutant lung cancer.
Authors: Sherr CJ PMID: 30214680 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

PKC ι and YAP1 are crucial in promoting pancreatic tumorigenesis.
PKCι and YAP1 are crucial in promoting pancreatic tumorigenesis. Oncotarget. 2018 Aug 28;9(67):32736-32750 Authors: Wang P, Wei D, Zhang H, Chen J, Zhang D, Ganapathy S, Isakson P, Chen C, Zhu T Abstract Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant disease with 5-year survival rate of less than 6%. Activating mutations of Kras (mu-Kras) are often detected in most of PDAC patients. Although it has been known that oncogenic Kras is the driver of pancreatic cancer initiation and development, the underlying mechanisms by which mu-Kras promotes PDAC remain poorly understood. Here, we id...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A novel, nontoxic iron chelator, super-polyphenol, effectively induces apoptosis in human cancer cell lines.
In conclusion, SP is a novel oral iron chelator with anti-cancer effects and few adverse side effects. This is the first report of SP in the literature. PMID: 30214682 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Differential signaling pathway activation in 7,12-dimethylbenz[a] anthracene (DMBA)-treated mammary stem/progenitor cells from species with varying mammary cancer incidence.
Authors: Ledet MM, Oswald M, Anderson R, Van de Walle GR Abstract A natural variation exists in the susceptibility to mammary cancer among wild and domestic mammalian species. Mammary stem/progenitor cells (MaSC) represent a primary target cell for transformation; however, little is known about the intrinsic response of these cells to carcinogenic insults. Polycyclic aromatic hydrocarbons (PAH), such as 7,12-dimethylbenz[a]anthracene (DMBA), are abundantly present in the environment and have been linked to the development of mammary cancer in humans and rodents. We treated MaSC from equine (mammary cancer-resistant...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

PLAGL1 gene function during hepatoma cells proliferation.
Authors: Vega-Benedetti AF, Saucedo CN, Zavattari P, Vanni R, Royo F, Llavero F, Zugaza JL, Parada LA Abstract Hepatocellular carcinoma develops as a multistep process, in which cell cycle deregulation is a central feature, resulting in unscheduled proliferation. The PLAGL1 gene encodes a homonym zinc finger protein that is involved in cell-proliferation control. We determined the genomic profile and the transcription and expression level of PLAGL1, simultaneously with that of its molecular partners p53, PPARγ and p21, in cell-lines derived from patients with liver cancer, during in vitro cell growth. Our inv...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Thymic stromal lymphopoietin in human pancreatic ductal adenocarcinoma: expression and prognostic significance.
Authors: Vizio B, Boita M, Cristiano C, Mazibrada J, Bosco O, Novarino A, Prati A, Sciascia S, Rolla G, Ciuffreda L, Montrucchio G, Bellone G Abstract Thymic stromal lymphopoietin (TSLP) has emerged as an important, but contradictory, player conditioning tumor growth. In certain contexts, by driving T helper (h) 2 responses via tumor-associated OX40 Ligand (OX40L)+ dendritic cells (DCs), TSLP may play a pro-tumorigenic role. The study elucidates the importance of TSPL in pancreatic ductal adenocarcinoma (PDAC), by analyzing: i) TSLP levels in PDAC cell-line supernatants and plasma from patients with locally-advance...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Bladder cancer detection by urinary extracellular vesicle mRNA analysis.
Conclusion: Three urinary EV mRNA were discovered to be elevated in bladder cancer. Urinary EV mRNA are promising biomarkers of urothelial cancer and worth further investigation. PMID: 30214686 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Vitamin C promotes decitabine or azacytidine induced DNA hydroxymethylation and subsequent reactivation of the epigenetically silenced tumour suppressor CDKN1A in colon cancer cells.
In this study, we set out to determine whether vitamin C can enhance the known anti-neoplastic actions of the DNA-demethylating agents decitabine (DAC) and azacytidine (AZA) in colorectal cancer cells. Administration of vitamin C alone significantly enhanced global levels of 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), without altering 5-methyl-2'-deoxycytidine (5-mdC), as would be expected upon the activation of TET dioxygenases. Concomitant treatment of vitamin C with either AZA or DAC resulted in an unexpectedly high increase of global 5-hmdC levels, one that administration of any these compounds alone could not achieve. ...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation.
Authors: Cresson C, Péron S, Jamrog L, Rouquié N, Prade N, Dubois M, Hébrard S, Lagarde S, Gerby B, Mancini SJC, Cogné M, Delabesse E, Delpy L, Broccardo C Abstract Pax5 is the guardian of the B cell identity since it primes or enhances the expression of B cell specific genes and concomitantly represses the expression of B cell inappropriate genes. The tight regulation of Pax5 is therefore required for an efficient B cell differentiation. A defect in its dosage can translate into immunodeficiency or malignant disorders such as leukemia or lymphoma. Pax5 is expressed from two different pr...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Beyond the 3'UTR binding-microRNA-induced protein truncation via DNA binding.
Authors: von Brandenstein M, Bernhart SH, Pansky A, Richter C, Kohl T, Deckert M, Heidenreich A, Stadler PF, Montesinos-Rongen M, Fries JWU Abstract Here, we present a miR mechanism which is active in the nucleus and is essential for the production of intron included, C-terminal truncated and biologically active proteins, like e.g. Vim3. We exemplified this mechanism by miRs, miR-15a and miR-498, which are overexpressed in clear cell renal carcinoma or oncocytoma. Both miRs directly interact with DNA in an intronic region, leading to transcriptional stop, and therefore repress the full length version of the pre-mRN...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Identification of a novel gene fusion in ALT positive osteosarcoma.
Authors: Mason-Osann E, Dai A, Floro J, Lock YJ, Reiss M, Gali H, Matschulat A, Labadorf A, Flynn RL Abstract The Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere elongation and prevents cellular senescence in approximately 60% of osteosarcoma. While the precise mechanism underlying activation of the ALT pathway is unclear, mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and the histone variant H3.3 correlate with ALT status. ATRX and DAXX facilitate deposition of the histone variant H3.3 within heterochromatic regions suggesting that loss of ATRX, DAXX, and/or H3.3...
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition.
Authors: Raneros AB, Minguela A, Rodriguez RM, Colado E, Bernal T, Anguita E, Mogorron AV, Gil AC, Vidal-Castiñeira JR, Márquez-Kisinousky L, Bulnes PD, Marin AM, García Garay MC, Suarez-Alvarez B, Lopez-Larrea C Abstract [This corrects the article DOI: 10.18632/oncotarget.16657.]. PMID: 30214691 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.
Authors: Jung H, Yoo HY, Lee SH, Shin S, Kim SC, Lee S, Joung JG, Nam JY, Ryu D, Yun JW, Choi JK, Ghosh A, Kim KK, Kim SJ, Kim WS, Park WY, Ko YH Abstract [This corrects the article DOI: 10.18632/oncotarget.14928.]. PMID: 30214692 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 16, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Distinguishing mechanisms of adverse drug reactions from mechanisms of actions of drugs.
Authors: Wu TH, Karim N, Moscow JA PMID: 30197750 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Clinical utility of chromatin analysis.
Authors: Kleppe A, Danielsen HE PMID: 30197751 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

An intestinal stem cell niche in Apc mutated neoplasia targetable by CtBP inhibition.
Authors: Chawla AT, Cororaton AD, Idowu MO, Damle PK, Szomju B, Ellis KC, Patel BB, Grossman SR Abstract C-terminal binding protein 2 (CtBP2) drives intestinal polyposis in the Apcmin mouse model of human Familial Adenomatous Polyposis. As CtBP2 is targetable by an inhibitor of its dehydrogenase domain, understanding CtBP2's role in adenoma formation is necessary to optimize CtBP-targeted therapies in Apc mutated human neoplasia. Tumor initiating cell (TIC) populations were substantially decreased in ApcminCtbp2+/- intestinal epithelia. Moreover, normally nuclear Ctbp2 was mislocalized to the cytoplasm of intestina...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A novel molecular mechanism for a long non-coding RNA PCAT92 implicated in prostate cancer.
Authors: Bawa PS, Ravi S, Paul S, Chaudhary B, Srinivasan S Abstract The role of many lncRNAs in cancer remains elusive including that for a Prostate Cancer Associated Transcript 92 (PCAT92). PCAT92 shares the locus on chromosome 13 with ABCC4 gene, known to be implicated in prostate cancer. It has been shown that PCAT92 and ABCC4 are up-regulated in prostate cancer samples from multiple transcriptome datasets. Among the prostate cancer cell-lines LNCaP showed maximum overexpression of PCAT92 compared to control cell-line RWPE-1. We have shown that knockdown of PCAT92 in LNCaP cells reduces cell viability and proli...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Integrin α2β1 decelerates proliferation, but promotes survival and invasion of prostate cancer cells.
Integrin α2β1 decelerates proliferation, but promotes survival and invasion of prostate cancer cells. Oncotarget. 2018 Aug 21;9(65):32435-32447 Authors: Ojalill M, Parikainen M, Rappu P, Aalto E, Jokinen J, Virtanen N, Siljamäki E, Heino J Abstract High expression level of integrin α2β1 is a hallmark of prostate cancer stem cell like cells. The role of this collagen receptor is controversial since it is down regulated in poorly differentiated carcinomas, but concomitantly proposed to promote metastasis. Here, we show that docetaxel resistant DU145 prostate cancer cells expres...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

"Two hits - one stone"; increased efficacy of cisplatin-based therapies by targeting PCNA's role in both DNA repair and cellular signaling.
In this study, we target the stress-related roles of the scaffold protein PCNA with a cell-penetrating peptide containing the PCNA-interacting motif APIM. The APIM-peptide increased the efficacy of cisplatin-based therapies in a muscle-invasive bladder cancer (MIBC) solid tumor model in rat and in bladder cancer (BC) cell lines. By combining multiple omics-levels, from gene expression to proteome/kinome and metabolome, we revealed a unique downregulation of the EGFR/ERBB2 and PI3K/Akt/mTOR pathways in the APIM-peptide-cisplatin combination treated cells. Additionally, the combination treatment reduced the expression of ant...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

SPIN1 is a proto-oncogene and SPIN3 is a tumor suppressor in human seminoma.
Authors: Janecki DM, Sajek M, Smialek MJ, Kotecki M, Ginter-Matuszewska B, Kuczynska B, Spik A, Kolanowski T, Kitazawa R, Kurpisz M, Jaruzelska J Abstract SPIN1 is necessary for normal meiotic progression in mammals. It is overexpressed in human ovarian cancers and some cancer cell lines. Here, we examined the functional significance and regulation of SPIN1 and SPIN3 in the TCam-2 human seminoma cell line. We found that while SPIN1 overexpression reduced apoptosis in these cells, SPIN3 overexpression induced it. Similarly, SPIN1 upregulated and SPIN3 downregulated CYCD1, which is a downstream target of the PI3K/AKT...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Zac1 regulates IL-11 expression in osteoarthritis.
Authors: Kuo CL, Liu ST, Chang YL, Wu CC, Huang SM Abstract Interleukin (IL)-11, a member of the IL-6 family of cytokines, exerts pleiotropic effects under normal and various disease conditions. We assessed IL-11 expression regulation and the IL-11/IL-6 ratio in osteoarthritis (OA) to better guide clinical therapeutic decision-making. Our findings suggest that Zac1, a zinc finger protein that regulates apoptosis and cell cycle arrest, is a transcription factor regulating IL-11 expression. Zac1 overexpression or knockdown respectively induced or suppressed IL-11 expression in HeLa cells. Zac1 acted synergistically w...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Therapeutic targeting of Aurora A kinase in Philadelphia chromosome-positive ABL tyrosine kinase inhibitor-resistant cells.
In this study, we investigated whether inhibiting Aurora kinase can reduce the viability of Ph+ leukemia cells. Treatment with the Aurora kinase A inhibitor alisertib blocked Ph+ leukemia cell proliferation and Aurora kinase A phosphorylation; it also induced G2/M-phase arrest and increased the intracellular levels of reactive oxygen species. Combined treatment of Ph+ cells with ABL TKIs and alisertib was cytotoxic, with the fraction of senescent cells increasing in a time- and dose-dependent manner. Aurora A gene silencing suppressed cell proliferation and enhanced ABL TKI efficacy. In a mouse xenograft model, co-administ...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

miR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell invasion in vitro.
This study reveals opposed effects of miR-193b / miR-30c-1* and miR-576-5p, respectively, on melanoma cell invasion and on expression of BCL9 and MCL1, possibly accounting for the contrasting invasive phenotypes observed in A375 cells transfected with these miRNAs. The miRNAs studied and their targets identified fit well into a model proposed by us explaining the regulation of invasion associated genes and the observed opposed phenotypes as a result of networked direct and indirect miRNA / target interactions. The results of this study suggest miR-193b and miR-30c-1* as tumor-suppressive miRNAs, whereas miR-576-5p appears ...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Genomic mutations and histopathologic biomarkers in Y90 radioembolization for chemorefractory colorectal liver metastases.
Authors: Dendy MS, Ludwig JM, Kokabi N, Stein SM, Lacy J, Hochster HS, Kim HS Abstract Background: To investigate mutational load and histologic biomarkers as prognostic factors in patients with chemorefractory colorectal liver metastases (CRLM) treated with Y-90 radioembolization therapy. Materials and Methods: Single institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patient demographics, systemic therapy regimens, tumor characteristics and overall survival were analyzed between patients with differing histopathologic and...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Approaches to the discovery of non-invasive urinary biomarkers of prostate cancer.
Authors: Jedinak A, Loughlin KR, Moses MA Abstract Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. Prostate specific antigen (PSA) measured in blood has been used for decades as an aid for physicians to detect the presence of prostate cancer. However, the PSA test has limited sensitivity and specificity, leading to unnecessary biopsies, overdiagnosis and overtreatment of patients. For these reasons, there is an urgent need for more accurate PCa biomarkers that can detect PCa with high sensitivity and specificity. Urine is a unique source of potential protein biomarkers that ca...
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Retraction: MicroRNA-371-5p targets SOX2 in gastric cancer.
Authors: Li YJ, Dong M, Kong FM, Zhou JP, Liang D, Xue HZ Abstract [This retracts the article DOI: 10.18632/oncotarget.8289.]. PMID: 30197762 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - September 12, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Prophylactic cranial irradiation (PCI) in locally advanced non-small cell lung cancer: time for hope?
Authors: De Ruysscher DK, Groen HJ PMID: 30190783 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Disabling an oncogenic transcription factor by targeting of control kinases.
Authors: Vakoc CR, Kentsis A PMID: 30190784 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A metabolic vulnerability of small-cell lung cancer.
Authors: Nomura M, Morita M, Tanuma N PMID: 30190785 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

xCT inhibition sensitizes tumors to γ-radiation via glutathione reduction.
xCT inhibition sensitizes tumors to γ-radiation via glutathione reduction. Oncotarget. 2018 Aug 17;9(64):32280-32297 Authors: Cobler L, Zhang H, Suri P, Park C, Timmerman LA Abstract About 3 million US cancer patients and 1.7 million EU cancer patients received multiple doses of radiation therapy (RT) in 2012, with treatment duration limited by normal adjacent tissue damage. Tumor-specific sensitization could allow treatment with lower radiation doses, reducing normal tissue damage. This is a longstanding, largely unrealized therapeutic goal. The cystine:glutamate exchanger xCT is expressed on po...
Source: Oncotarget - September 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Immune checkpoint inhibitor re-challenge in patients with advanced non-small cell lung cancer.
Conclusion: Our study shows the effectiveness of re-challenge of immune checkpoint inhibitors in a subset of non-small cell lung cancer patients. Re-challenge might become one of treatment option for advanced non-small cell lung cancer. PMID: 30190787 [PubMed] (Source: Oncotarget)
Source: Oncotarget - September 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Terpenes from essential oils and hydrolate of Teucrium alopecurus triggered apoptotic events dependent on caspases activation and PARP cleavage in human colon cancer cells through decreased protein expressions.
This study focused on characterizing the Hydrophobic and Hydrophilic fractions of Teucrium alopecurus in the context of cancer prevention and therapy. The goal was also to elucidate the molecular mechanisms involved and to determine its efficacy against cancer by triggering apoptosis and suppressing tumorigenesis in human colon cancer. The data here clearly demonstrated that oily fractions of Teucrium alopecurus act as free radical scavengers, antibacterial agent and inhibited the proliferation of HCT-116, U266, SCC4, Panc28, KBM5, and MCF-7 cells in a time- and concentration-dependent manner. The results of live/dead and ...
Source: Oncotarget - September 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research