Identification of mobile lipids in human cancer tissues by ex vivo diffusion edited HR-MAS MRS

AbstractTechnologies required to generate induced pluripotent stem cells (iPSC) were first described 15 years ago, providing a strong impetus to the field of regenerative medicine. In parallel, immunotherapy has finally emerged as a clinically meaningful modality of cancer therapy. In particular, impressive efficacy has been achieved in patients with selected haematological malignancies using ex vivo expanded autologous T cells engineered to express chimeric antigen receptors (CARs). While solid tumours account for over 90% of human cancer, they currently are largely refractory to this therapeutic approach. Nonetheless, given the considerable innovation taking place worldwide in the CAR field, it is likely that effective solutions for common solid tumours will emerge in the near future. Such a development will create significant new challenges in the scalable delivery of these complex, costly and individualised therapies. CAR-engineered immune cell products that originate from iPSCs offer the potential to generate unlimited numbers of homogeneous, standardised cell products in which multiple defined gene modification events have been introduced to ensure safety, potency and reproducibility. Here, we review some of the emerging strategies in use to engineer CAR-expressing iPSC-derived drug products.

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Identification of αB-Crystallin, a Biomarker of Renal Cell Carcinoma by SELDI-TOF MS

The International Journal of Biological Markers ◽

10.1177/172460080802300108 ◽

2008 ◽

Vol 23 (1) ◽

pp. 48-53 ◽

Cited By ~ 1

Author(s):

J. Holcakova ◽

L. Hernychova ◽

P. Bouchal ◽

K. Brozkova ◽

J. Zaloudik ◽

...

Keyword(s):

Renal Cell ◽

Human Cancer ◽

Biological Fluids ◽

Serum Markers ◽

Circulating Biomarkers ◽

Surface Enhanced ◽

Αb Crystallin ◽

Specific Proteins ◽

Low Levels ◽

Cancer Tissues

Spectrometric-based surface-enhanced laser desorption/ionization ProteinChip (SELDI-TOF) facilitates rapid and easy analysis of protein mixtures and is often exploited to define potential diagnostic markers from sera. However, SELDI-TOF is a relatively insensitive technique and unable to detect circulating proteins at low levels even if they are differentially expressed in cancer patients. Therefore, we applied this technology to study tissues from renal cell carcinomas (RCC) in comparison to healthy controls. We found that different biomarkers are identified from tissues than those previously identified in serum, and that serum markers are often not produced by the tumors themselves at detectable levels, reflecting the nonspecific nature of many circulating biomarkers. We detected and characterized αB-crystallin as an overexpressed protein in RCC tissues and showed differential expression by immunohistochemistry. We conclude that SELDI-TOF is more useful for the identification of biomarkers that are synthesized by diseased tissues than for the identification of serum biomarkers and identifies a separate set of markers. We suggest that SELDI-TOF should be used to screen human cancer tissues to identify potential tissue-specific proteins and simpler and more sensitive techniques can then be applied to determine their validity as biomarkers in biological fluids.

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IRF6 and TAK1 coordinately promote the activation of HIPK2 to stimulate apoptosis during palate fusion

Science Signaling ◽

10.1126/scisignal.aav7666 ◽

2019 ◽

Vol 12 (593) ◽

pp. eaav7666 ◽

Cited By ~ 2

Author(s):

Chen-Yeh Ke ◽

Hua-Hsuan Mei ◽

Fen-Hwa Wong ◽

Lun-Jou Lo

Keyword(s):

Transcription Factor ◽

Cell Apoptosis ◽

Transforming Growth Factor ◽

Kinase Inhibitor ◽

Ex Vivo ◽

Human Cancer ◽

Ectopic Expression ◽

Interacting Protein ◽

Human Cancer Cells

Cleft palate is a common craniofacial defect caused by a failure in palate fusion. The palatal shelves migrate toward one another and meet at the embryonic midline, creating a seam. Transforming growth factor–β3 (TGF-β3)–induced apoptosis of the medial edge epithelium (MEE), the cells located along the seam, is required for completion of palate fusion. The transcription factor interferon regulatory factor 6 (IRF6) promotes TGF-β3–induced MEE cell apoptosis by stimulating the degradation of the transcription factor ΔNp63 and promoting the expression of the gene encoding the cyclin-dependent kinase inhibitor p21. Because homeodomain-interacting protein kinase 2 (HIPK2) functions downstream of IRF6 in human cancer cells and is required for ΔNp63 protein degradation in keratinocytes, we investigated whether HIPK2 played a role in IRF6-induced ΔNp63 degradation in palate fusion. HIPK2 was present in the MEE cells of mouse palatal shelves during seam formation in vivo, and ectopic expression of IRF6 in palatal shelves cultured ex vivo stimulated the expression of Hipk2 and the accumulation of phosphorylated HIPK2. Knockdown and ectopic expression experiments in organ culture demonstrated that p21 was required for HIPK2- and IRF6-dependent activation of caspase 3, MEE apoptosis, and palate fusion. Contact between palatal shelves enhanced the phosphorylation of TGF-β–activated kinase 1 (TAK1), which promoted the phosphorylation of HIPK2 and palate fusion. Our findings demonstrate that HIPK2 promotes seam cell apoptosis and palate fusion downstream of IRF6 and that IRF6 and TAK1 appear to coordinately enhance the abundance and activation of HIPK2 during palate fusion.

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MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14768374457986 ◽

2017 ◽

Vol 25 (4) ◽

pp. 617-627 ◽

Cited By ~ 27

Author(s):

Chunsheng Li ◽

Jingrong Dong ◽

Zhenqi Han ◽

Kai Zhang

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Cell Lines ◽

Human Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

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Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map

Cancer Informatics ◽

10.4137/cin.s39839 ◽

2016 ◽

Vol 15 ◽

pp. CIN.S39839 ◽

Cited By ~ 13

Author(s):

Akimasa Seno ◽

Tomonari Kasai ◽

Masashi Ikeda ◽

Arun Vaidyanath ◽

Junko Masuda ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Cancer Stem Cells ◽

Human Cancer ◽

Expression Patterns ◽

Embryonic Stem ◽

Culture Conditions ◽

Self Organizing Map ◽

Cancer Tissues ◽

Self Organizing

We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors ( OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes ( POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs.

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Abstract 949: PathSeq: A comprehensive computational tool for pathogen discovery by deep sequencing of human cancer tissues

10.1158/1538-7445.am2011-949 ◽

2011 ◽

Author(s):

Akinyemi I. Ojesina ◽

Aleksandar Kostic ◽

Chandra Sekhar Pedamallu ◽

Joonil Jung ◽

Fujiko Duke ◽

...

Keyword(s):

Deep Sequencing ◽

Human Cancer ◽

Computational Tool ◽

Pathogen Discovery ◽

Cancer Tissues

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Clinical significance of ERas oncogene on cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15083 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15083-15083

Author(s):

K. Yasuda ◽

M. Yashiro ◽

T. Sawada ◽

M. Ohira ◽

K. Hirakawa

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Es Cells ◽

Cancer Cell Lines ◽

Colorectal Cancers ◽

Breast Cancers ◽

Cancer Tissues

15083 Background: Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. When ES cells are subcutaneously injected into immunodeficient or isogenic mice, a teratoma is formed within a few weeks. This tumor is composed of all three germ layers in a disorganized fashion. Thus there could be some common molecular mechanisms shared by ES cells and somatic cancer cells. The ERas oncogene is a recently identified gene that supports the tumorigenic growth of ES cells by producing a constitutively active Ras protein. There have been no report about expression of ERas oncogene on cancer cells until now. The aim of this study is to investigate expression and clinical significance of ERas oncogene on cancer cell lines and clinical cancer tissues. Methods: A panel of 35 human cancer cell lines, 5 normal cell lines, and 20 patiants with gastric cancer tissues were used in this study. ERas mRNA expression was examined by reverse transcription-polymerase chain reaction. The effect of the DNA methyl transferase inhibitor, 5-aza-2’- deoxycitydine on the ERas expression was analyzed. Methylation of CpG islands of ERas promoter lesion was investigated using bisulfate-directsequence analysis. Results: Expression of ERas mRNA was not found in any normal cells. In contrast, ERas mRNA was found in 15 of 35 cancer cell lines, including 8 of 15 gastric cancers, 4 of 7 colorectal cancers, 2 of 6 pancreas cancers, 1 of 3 breast cancers and none of esophageal cancers. Eras mRNA was found in all gastric cancer tissues, but not normal tissues. 5-aza-2’-deoxycytidine treatment at 2, 5, and 10μM for 24 h resulted in ERas expression in 10 of 20 cancer cell lines with respect to the silencing of ERas, including 7 of 7 gastric cancers, 1 of 3 colorectal cancers and 2 of 3 breast cancers. Methylation of CpG island were found in the cancer cell lines without ERas expression, but not in these with ERas expression. Conclusions: ERas oncogene is associated with the carcinogenesis pathway in human cancer. Eras might be useful marker for cancer diagnosis. No significant financial relationships to disclose.

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Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cell lines characterized for EGFR expression and K-ras mutation

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14583 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14583-e14583 ◽

Cited By ~ 1

Author(s):

J. Barriere ◽

J. Fischel ◽

P. Formento ◽

N. Renée ◽

M. Francoual ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Mononuclear Cells ◽

Kinase Inhibitor ◽

Ex Vivo ◽

Human Cancer ◽

Tumor Cell Lines ◽

Ras Mutation ◽

Egfr Expression ◽

Mutational Status

e14583 Background: Mutated K-ras protein is a strong predictive factor of cetuximab resistance, bypassing the classical direct inhibitory effect on epidermal growth factor receptor (EGFR) signaling. However, cetuximab is also able to mediate ADCC, which may be part of the clinical response. The aim of this ex-vivo study was to quantify cetuximab-mediated ADCC on various human cancer cell lines characterized for EGFR-expression and K-ras mutation. Methods: Two K-ras mutated cell lines over-expressing EGFR and resistant to anti-EGFR tyrosine kinase inhibitor were tested (Capan-1 and Capan-2, pancreatic), along with 2 K-ras wild-type cell lines over- expressing EGFR (CAL166, head and neck; A431, epidermoid carcinoma) and an EGFR-negative cell line (OCM1, uveal melanoma). The tested monoclonal antibodies (mAbs) were: cetuximab (Merck, anti-EGFR IgG1 mAb), panitumumab (Amgen, anti-EGFR IgG2 mAb), and as a negative control, rituximab (Roche, IgG1 anti-CD20 mAb). ADCC (51Cr release assay) was performed using freshly- isolated peripheral blood mononuclear cells from a healthy donor. Results were expressed as % of potentially maximum 51Cr release. Results: Cetuximab mediates ADCC against EGFR-over-expressing cell lines CAL166 (38.4 ± 3.1 %), A431 (13.5 ± 1.7 %), Capan-1 (31.2 ± 0.8 %) and Capan-2 (27.8 ± 8.6 %) irrespective of the K-ras mutational status, but not against EGFR-negative OCM-1 (6.2 ± 1 %). Conversely, unlike IgG1 cetuximab, the anti-EGFR IgG2 panitumumab and the irrelevant antibody rituximab were both unable to induce significant ADCC (< 10 % on all tested cell lines). Conclusions: Cetuximab-mediated ADCC is independent of the K-ras mutational status of the tumor cell lines. Present data suggest that cetuximab may remain of clinical interest in K-ras-mutated patients. Immunostimulation, as well as new generation anti-EGFR mAbs with improved ability to induce ADCC, may be promising in the management of K-ras-mutated patients. No significant financial relationships to disclose.

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Cell Transfer Therapy for Cancer: Past, Present, and Future

Journal of Immunology Research ◽

10.1155/2014/525913 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

Xiaoling Qian ◽

Xian Wang ◽

Hongchuan Jin

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

Nk Cells ◽

Human Cancer ◽

Tumor Infiltrating Lymphocytes ◽

Cell Transfer ◽

Human Cancer Cells ◽

Cancer Tissues ◽

Infiltrating Lymphocytes

Cell transfer therapy for cancer has made a rapid progress recently and the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs). In vitro activated or engineered immune cells can traffic to cancer tissues to elicit persistent antitumor immune response which is very important especially after immunosuppressive treatments such as chemotherapy. In this review, we overviewed recent advances in the exploration of dendritic cells, NK cells, and T cells for the treatment of human cancer cells.

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