Journals Neoplasia : An International J...

Neoplasia : An International Journal for Oncology Research
Susanne G Kidd, Kristina T Carm, Mari Bogaard, Linn Guro Olsen, Anne Cathrine Bakken, Marthe Løvf, Ragnhild A Lothe, Karol Axcrona, Ulrika Axcrona, Rolf I Skotheim
In primary prostate cancer, the common multifocality and heterogeneity are major obstacles in finding robust prognostic tissue biomarkers. The long noncoding RNA SCHLAP1 has been suggested, but its prognostic value has not been investigated in the context of tumor heterogeneity. In the present study, expression of SCHLAP1 was investigated using real-time RT-PCR in a multisampled series of 778 tissue samples from radical prostatectomies of 164 prostate cancer patients (median follow-up time 7.4 y). The prognostic value of SCHLAP1 was evaluated with biochemical recurrence as endpoint...
June 6, 2021: Neoplasia: An International Journal for Oncology Research
Joanna S Yi, Oscar Sias-Garcia, Nicole Nasholm, Xiaoyu Hu, Amanda Balboni Iniguez, Matthew D Hall, Mindy Davis, Rajarshi Guha, Myrthala Moreno-Smith, Eveline Barbieri, Kevin Duong, Jessica Koach, Jun Qi, James E Bradner, Kimberly Stegmaier, William A Weiss, W Clay Gustafson
Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi...
June 6, 2021: Neoplasia: An International Journal for Oncology Research
Kotaro Sato, Kshitij Parag-Sharma, Masahiko Terajima, Adele M Musicant, Ryan M Murphy, Matthew R Ramsey, Hideharu Hibi, Mitsuo Yamauchi, Antonio L Amelio
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. HNSCC patient prognosis is closely related to the occurrence of tumor metastases, and collagen within the tumor microenvironment (TME) plays a key role in this process. Lysyl hydroxylase 2 (LH2), encoded by the Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2 (PLOD2) gene, catalyzes hydroxylation of telopeptidyl lysine (Lys) residues of fibrillar collagens which then undergo subsequent modifications to form stable intermolecular cross-links that change the biomechanical properties (i...
June 6, 2021: Neoplasia: An International Journal for Oncology Research
Sarah Müller, Stefanie Mayer, Peter Möller, Thomas F E Barth, Ralf Marienfeld
The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenocarcinoma heterogeneity is discussed to be a reason for therapy failure using targeted therapy or immune checkpoint inhibitors. For successful therapy of immune checkpoint inhibitors the expression and distribution of the involved immune checkpoint proteins is essential...
June 5, 2021: Neoplasia: An International Journal for Oncology Research
Hui Xu, Xiaomei Yang, Xiaofeng Xuan, Di Wu, Jieru Zhang, Xinchun Xu, Yuanjie Zhao, Chunping Ma, Dawei Li
Tumor metastasis is a leading cause of death in lung adenocarcinoma (LUAD) patients, but the molecular events that regulate metastasis have not been completely elucidated. STAMBP is a deubiquitinating enzyme of the Jab1/MPN metalloenzyme family that regulates the stability of substrates in cells by specifically removing ubiquitin molecules. We found that STAMBP expression was increased in the cytoplasm of tumor cells from LUAD patients. The STAMBP level was closely associated with tumor size, lymph node invasion and neoplasm disease stage...
June 4, 2021: Neoplasia: An International Journal for Oncology Research
Gaurav Kumar, Venkateshwar Madka, Anil Singh, Mudassir Farooqui, Nicole Stratton, Stanley Lightfoot, Altaf Mohammed, Chinthalapally V Rao
Lung cancer is the leading cause of cancer related deaths worldwide. The present study investigated the effects of naproxen (NSAID) on lung adenocarcinoma in spontaneous lung cancer mouse model. Six-week-old transgenic KrasG12V mice (n = 20; male + female) were fed modified AIN-76A diets containing naproxen (0/400 ppm) for 30 wk and euthanized at 36 wk of age. Lungs were evaluated for tumor incidence, multiplicity, and histopathological stage (adenoma and adenocarcinoma). Lung tumors were noticeable as early as 12 wk of age exclusively in the KrasG12V mice...
June 3, 2021: Neoplasia: An International Journal for Oncology Research
Bo-Ram Jin, Kyung-Sook Chung, Soonjae Hwang, Sam Noh Hwang, Ki-Jong Rhee, Minho Lee, Hyo-Jin An
Previously, we found that rosmarinic acid (RA) exerted anti-inflammatory activities in a dextran sulfate sodium (DSS)-induced colitis model. Here, we investigated the anti-tumor effects of RA on colitis-associated colon cancer (CAC) and the underlying molecular mechanisms. We established an azoxymethane (AOM)/DSS-induced CAC murine model for in vivo studies and used a conditioned media (CM) culture system in vitro. H&E staining, immunohistochemistry, western blot assay, enzyme-linked immunosorbent assay, molecular docking, co-immunoprecipitation, and immunofluorescence assay were utilized to investigate how RA prevented colorectal cancer...
May 30, 2021: Neoplasia: An International Journal for Oncology Research
Runping Fang, Lihong Ye, Hui Shi
Breast cancer is believed to be driven by epigenetic regulation of genes implicated in cell proliferation, survival, and differentiation. Recently, aberrant N6 -methyladenosine (m6 A) decorations turned up as crucial epigenetic regulator for malignant breast cancer, which may serve as new targets for breast cancer treatment. Here we briefly outline the functions of m6 A and its regulatory proteins, including m6 A "writers," "readers," and "erasers" on RNA life fate, recapitulate the latest breakthroughs in understanding m6 A modification and its regulatory proteins, and the underlying molecular mechanisms that contribute to the carcinogenesis and the progression of breast cancer, so as to provide potential epigenetic targets for diagnosis, treatment and prognosis in breast cancer...
May 14, 2021: Neoplasia: An International Journal for Oncology Research
Noreen McBrearty, Alla Arzumanyan, Eugene Bichenkov, Salim Merali, Carmen Merali, Mark Feitelson
Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The HBV encoded oncoprotein, HBx, alters the expression of host genes and the activity of multiple signal transduction pathways that contribute to the pathogenesis of HCC by multiple mechanisms independent of HBV replication. However, it is not clear which pathways are the most relevant therapeutic targets in hepatocarcinogenesis. Short chain fatty acids (SCFAs) have strong anti-inflammatory and anti-neoplastic properties, suggesting that they may block the progression of chronic liver disease (CLD) to HCC, thereby identifying the mechanisms relevant to HCC development...
May 1, 2021: Neoplasia: An International Journal for Oncology Research
María Ovejero-Sánchez, Rogelio González-Sarmiento, Ana Belén Herrero
Ovarian cancer (OC) is the deadliest gynecologic malignancy, which is mainly due to late-stage diagnosis and chemotherapy resistance. Therefore, new and more effective treatments are urgently needed. The in vitro effects of Panobinostat (LBH), a histone deacetylase inhibitor that exerts pleiotropic antitumor effects but induces autophagy, in combination with Chloroquine (CQ), an autophagy inhibitor that avoid this cell survival mechanism, were evaluated in 4 OC cell lines. LBH and CQ inhibited ovarian cancer cell proliferation and induced apoptosis, and a strong synergistic effect was observed when combined...
April 27, 2021: Neoplasia: An International Journal for Oncology Research
Tiane Chen, Maged Zeineldin, Blake A Johnson, Yi Dong, Akshay Narkar, Taibo Li, Jin Zhu, Rong Li, Tatianna C Larman
Although much is known about the gene mutations required to drive colorectal cancer (CRC) initiation, the tissue-specific selective microenvironments in which neoplasia arises remains less characterized. Here, we determined whether modulation of intestinal stem cell niche morphogens alone can exert a neoplasia-relevant selective pressure on normal colonic epithelium. Using adult stem cell-derived murine colonic epithelial organoids (colonoids), we employed a strategy of sustained withdrawal of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibition to select for and expand survivors...
April 23, 2021: Neoplasia: An International Journal for Oncology Research
Anne Gaza, Valerie Fritz, Lara Malek, Laura Wormser, Nora Treiber, Johannes Danner, Andreas E Kremer, Wolfgang E Thasler, Jürgen Siebler, Gunter Meister, Markus F Neurath, Claus Hellerbrand, Anja K Bosserhoff, Peter Dietrich
The poor prognosis of advanced hepatocellular carcinoma (HCC) is driven by diverse features including dysregulated microRNAs inducing drug resistance and stemness. Lin-28 homolog A (LIN28A) and its partner zinc finger CCHC-type containing 11 (ZCCHC11) cooperate in binding, oligouridylation and subsequent degradation of tumorsuppressive let-7 precursor microRNAs. Functionally, activation of LIN28A was recently shown to promote stemness and chemoresistance in HCC. However, the expression and regulation of LIN28A in HCC had been unclear...
April 23, 2021: Neoplasia: An International Journal for Oncology Research
Sandra N Freiberger, Muriel Brada, Christine Fritz, Sylvia Höller, Alexander Vogetseder, Milo Horcic, Michel Bihl, Michal Michal, Martin Lanzer, Martin Wartenberg, Urs Borner, Peter K Bode, Martina A Broglie, Tamara Rordorf, Grégoire B Morand, Niels J Rupp
Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms...
April 17, 2021: Neoplasia: An International Journal for Oncology Research
Shanwen Chen, Dingfang Bu, Jing Zhu, Taohua Yue, Shihao Guo, Xin Wang, Yisheng Pan, Yucun Liu, Pengyuan Wang
Increased xCT and transsulfuration pathway has been associated with metabolic reprogramming of colorectal cancer. However, the correlation between these 2 events and the underlying molecular mechanism remains obscure. xCT expression was determined in tissue microarrays of colorectal cancer. RNA sequencing and functional assays in vitro was adopted to delineate the involvement of transsulfuration pathway in the proper function of xCT in maintaining the chemoresistant phenotype. The synthetic lethality of blocking xCT and the transsulfuration pathway was investigated both in vitro and in vivo...
April 17, 2021: Neoplasia: An International Journal for Oncology Research
Huaqin Yuan, Xiaoxin Meng, Wenjie Guo, Peifen Cai, Wanshuai Li, Qian Li, Weicheng Wang, Yang Sun, Qiang Xu, Yanhong Gu
No abstract text is available yet for this article.
April 17, 2021: Neoplasia: An International Journal for Oncology Research
Diogo de Oliveira Pessoa, Flávia Eichemberger Rius, Debora D'Angelo Papaiz, Ana Luísa Pedroso Ayub, Alice Santana Morais, Camila Ferreira de Souza, Vinicius Ferreira da Paixão, João Carlos Setubal, Julia Newton-Bishop, Jérémie Nsengimana, Hatylas Azevedo, Eduardo Moraes Reis, Miriam Galvonas Jasiulionis
Despite advances in therapeutics, the progression of melanoma to metastasis still confers a poor outcome to patients. Nevertheless, there is a scarcity of biological models to understand cellular and molecular changes taking place along disease progression. Here, we characterized the transcriptome profiles of a multi-stage murine model of melanoma progression comprising a nontumorigenic melanocyte lineage (melan-a), premalignant melanocytes (4C), nonmetastatic (4C11-) and metastasis-prone (4C11+) melanoma cells...
April 9, 2021: Neoplasia: An International Journal for Oncology Research
Jeremy Johnson, Zeta Chow, Eun Lee, Heidi L Weiss, B Mark Evers, Piotr Rychahou
Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization...
April 8, 2021: Neoplasia: An International Journal for Oncology Research
Marco Trerotola, Emanuela Guerra, Zeeshan Ali, Anna Laura Aloisi, Martina Ceci, Pasquale Simeone, Angela Acciarito, Paola Zanna, Giovanna Vacca, Antonella D'Amore, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, Rossano Lattanzio, Saverio Alberti
Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. No Trop-2 cleavage was detected in normal human tissues, whereas most tumors showed Trop-2 cleavage, including skin, ovary, colon, and breast cancers...
April 8, 2021: Neoplasia: An International Journal for Oncology Research
Amiskwia Pöschel, Erin Beebe, Laura Kunz, Parisa Amini, Franco Guscetti, Alexandra Malbon, Enni Markkanen
Cancer-associated stroma (CAS) profoundly influences progression of tumors including mammary carcinoma (mCA). Canine simple mCA represent relevant models of human mCA, notably also with respect to CAS. While transcriptomic changes in CAS of mCA are well described, it remains unclear to what extent these translate to the protein level. Therefore, we sought to gain insight into the proteomic changes in CAS and compare them with transcriptomic changes in the same tissue. To this end, we analyzed CAS and matched normal stroma using laser-capture microdissection (LCM) and LC-MS/MS in a cohort of 14 formalin-fixed paraffin embedded (FFPE) canine mCAs that we had previously characterized using LCM-RNAseq...
March 29, 2021: Neoplasia: An International Journal for Oncology Research
Shiqi Ma, Shijun Jia, Yuan Ren, Bangrong Cao, Xiao Zha, Jintao He, Changmin Chen
No abstract text is available yet for this article.
March 28, 2021: Neoplasia: An International Journal for Oncology Research
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