• apoptosis
• low‐level laser
• oral mucositis
• photobiomodulation
• squamous cell carcinoma

• Humans
• Apoptosis/radiation effects
• Cell Survival/radiation effects
• Low-Level Light Therapy
• Cell Line, Tumor
• bcl-2-Associated X Protein/genetics
• bcl-2-Associated X Protein/metabolism
• Stomatitis/radiotherapy
• Stomatitis/pathology
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/radiotherapy
• Mouth Neoplasms/pathology
• Mouth Neoplasms/radiotherapy
• Proto-Oncogene Proteins c-bcl-2/genetics
• Proto-Oncogene Proteins c-bcl-2/metabolism

• 51608 Tehran University of Medical Sciences and Health Services

• National Natural Science Foundation of China

• copper-64
• folate
• ovarian cancer
• porphyrin
• positron emission tomography
• radiotherapy
• theragnostic
• water-soluble

• Animals
• Humans
• Mice
• Female
• Copper Radioisotopes/chemistry
• Positron-Emission Tomography/methods
• Cell Line, Tumor
• Ovarian Neoplasms/diagnostic imaging
• Ovarian Neoplasms/metabolism
• Porphyrins/chemistry
• Folate Receptor 1/metabolism
• Tissue Distribution
• Mice, Nude
• Radiopharmaceuticals/pharmacokinetics
• Radiopharmaceuticals/chemistry
• Folic Acid/chemistry
• Xenograft Model Antitumor Assays

• HeLa cell line
• STR profiling
• cross-contamination
• nasopharyngeal carcinoma

• Humans
• Nasopharyngeal Carcinoma/metabolism
• HeLa Cells
• Nasopharyngeal Neoplasms/metabolism
• Cell Line, Tumor
• Neoplasm Recurrence, Local/metabolism
• Nasopharynx/metabolism
• Nasopharynx/pathology

• Anticancer effects
• Apoptosis
• Autophagy
• Cervical cancer
• PI3K/Akt/mTOR pathway
• Piperlongumine

• oncolytic virus
• orthoreovirus
• pelareorep
• reovirus
• virotherapy
• zoonotic spillover

• Humans
• MAP Kinase Signaling System
• Heme Oxygenase-1
• Carcinoma, Squamous Cell/drug therapy
• Squamous Cell Carcinoma of Head and Neck
• Mouth Neoplasms/drug therapy
• Apoptosis
• JNK Mitogen-Activated Protein Kinases
• Head and Neck Neoplasms
• Cell Line, Tumor
• p38 Mitogen-Activated Protein Kinases

• Chung Shan Medical University Hospital

• enhanced permeability and retention (EPR) effect
• nanocarriers
• nanoparticle
• positron emission tomography (PET)
• prostate cancer theranostics
• prostate-specific membrane antigen (PSMA)
• radioligand theranostics
• radiopharmaceutical therapy
• small-molecule PSMA inhibitors

• R01CA266666 National Institute of Health (NIH)
• P30 CA082103 NCI NIH HHS
• R01 CA266666 NCI NIH HHS
• P30CA082103 Cancer Center Support Grant
• W81XWH-20-1-0292 US Department of Defense

• Zingiberaceae
• bis-labdanic diterpenes
• cytotoxicity
• labdane diterpenes
• norlabdane diterpenes

• CR cells
• MiniPDX
• PDX
• cancer models
• organoid

• Humans
• Mice
• Animals
• Disease Models, Animal
• Neoplasms
• Organoids
• Precision Medicine/methods
• Heterografts

User measurement bias during subcutaneous tumor measurement is a source of variation in preclinical in vivo studies. We investigated whether this user variability could impact efficacy study outcomes, in the form of the false negative result rate when comparing treated and control groups. Two tumor measurement methods were compared; calipers which rely on manual measurement, and an automatic 3D and thermal imaging device. Tumor growth curve data were used to create an in silico efficacy study with control and treated groups. Before applying user variability, treatment group tumor volumes were statistically different to the control group. Utilizing data collected from 15 different users across 9 in vivo studies, user measurement variability was computed for both methods and simulation was used to investigate its impact on the in silico study outcome. User variability produced a false negative result in 0.7% to 18.5% of simulated studies when using calipers, depending on treatment efficacy. When using an imaging device with lower user variability this was reduced to 0.0% to 2.6%, demonstrating that user variability impacts study outcomes and the ability to detect treatment effect. Reducing variability in efficacy studies can increase confidence in efficacy study outcomes without altering group sizes. By using a measurement device with lower user variability, the chance of missing a therapeutic effect can be reduced and time and resources spent pursuing false results could be saved. This improvement in data quality is of particular interest in discovery and dosing studies, where being able to detect small differences between groups is crucial.

• tumor models
• in silico
• in vivo
• tumor imaging
• 3d-ti
• study reproducibility
• efficacy study

Less than 0.5% of intravenously injected drugs reach tumors, contributing to side effects. To limit damage to healthy cells, various delivery vectors have been formulated; yet, previously developed vectors suffer from poor penetration into solid tumors. This issue was resolved by the discovery of HN-1 peptide isolated via biopanning a phage-display library. HN-1 targets human head and neck squamous cell carcinoma (HNSCC) (breast, thyroid; potentially lung, cervix, uterine, colon cancer), translocates across the cell membrane, and efficiently infiltrates solid tumors. HN-1 peptide has been conjugated to various anticancer drugs and imaging agents though the identity of its receptor remained enigmatic.

To decipher the clues that pointed to retinoblastoma (Rb)-regulated discoidin-domain receptor 1 as the putative receptor for HN-1 is described.

HN-1 peptide was synthesized and purified using reverse-phase high-performance liquid chromatography and gel electrophoresis. The predicted mass was confirmed by mass spectroscopy. To image the 3-dimensional structure of HN-1 peptide, PyMOL was used. Molecular modeling was also performed with PEP-FOLD3 software via RPBS bioinformatics web portal (INSERM, France). The immunohistochemistry results of discoidin domain receptor 1 (DDR1) protein were obtained from the publicly accessible database in the Human Protein Atlas portal, which contained the images of immunohistochemically labeled human cancers and the corresponding normal tissues.

The clues that led to DDR1 involved in metastasis as the putative receptor mediating HN-1 endocytosis are the following: (1) HN-1 is internalized in phosphate-buffered saline and its uptake is competitively inhibited; (2) HN-1 (TSPLNIHNGQKL) exhibits similarity with a stretch of amino acids in alpha5 beta3 integrin (KLLITIHDRKEF). Aside from two identical residues (Ile-His) in the middle, the overall distribution of polar and nonpolar residues throughout the sequences is nearly identical. As HN-1 sequence lacks the Arg-Gly-Asp motif recognized by integrins, HN-1 may interact with an "integrin-like" molecule. The tertiary structure of both peptides showed similarity at the 3-dimensional level; (3) HN-1 is internalized by attached cells but not by suspended cells. As culture plates are typically coated with collagen, collagen-binding receptor (expressed by adherent but not suspended cells) may represent the receptor for HN-1; (4) DDR1 is highly expressed in head and neck cancer (or breast cancer) targeted by HN-1; (5) Upon activation by collagen, DDR1 becomes internalized and compartmentalized in endosomes consistent with the determination of ’energy-dependent clathrin-mediated endocytosis’ as the HN-1 entry route and the identification of HN-1 entrapped vesicles as endosomes; and (6) DDR1 is essential for the development of mammary glands consistent with the common embryonic lineage rationale used to identify breast cancer as an additional target of HN-1. In summary, collagen-activated tyrosine kinase receptor DDR1 overexpressed in HNSCC assumes a critical role in metastasis. Further studies are warranted to assess HN-1 peptide’s interaction with DDR1 and the therapeutic potential of treating metastatic cancer. Additionally, advances in delivery (conformation, endocytic mechanism, repertoire of targeted cancers of HN-1 peptide), tracking (HN-1 conjugated imaging agents), and activity (HN-1 conjugated therapeutic agents) are described.

The discovery of DDR1 as HN-1 peptide’s putative receptor represents a significant advance as it enables identification of metastatic cancers or clinical application of previously developed therapeutics to block metastasis.

• HN-1 peptide
• Solid tumor
• Targeted drug delivery
• Discoidin domain receptor 1
• Tyrosine kinase
• Metastasis

Despite continuous advances, anticancer therapy still faces several technical hurdles, such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, trimethine cyanine dye, and folate to target the mitochondria of tumor cells. A series of proapoptotic peptides and their conjugates with a cyanine dye and/or folate were synthesized in the solid phase, and their toxicity in different human cell lines was assessed. Cyanine-bearing conjugates were found to be up to 100-fold more cytotoxic than the parent peptides and to localize in mitochondria. However, the addition of a folate motif did not enhance the potency or selectivity of the resulting conjugates toward tumor cells that overexpress folate receptor α. Furthermore, while dual-labeled constructs were also found to localize within the target organelle, they were not generally selective towards folate receptor α-positive cell lines in vitro.

• biomedical resources
• cell line authentication
• journal guidelines
• replication crisis
• reporting standards

• Animals
• Antibodies
• Biomedical Research/standards
• Cell Line
• Disease Models, Animal
• Editorial Policies
• Humans
• Periodicals as Topic/standards
• Publishing/standards

• 3D aggregates
• Cell lines
• organoids
• precision medicine
• xenografts

• Acetobacter syzygii
• Carcinogenesis
• Lactobacillus plantarum
• Lactobacillus salivarius
• Oral cancer
• Probiotics

• Carcinogenesis
• Humans
• Malaysia
• Mouth Neoplasms/prevention & control
• Probiotics

• actin disruption
• apoptosis
• cancer
• scytophycines
• tolytoxin

Cell lines are widely used in research and for diagnostic tests and are often shared between laboratories. Lack of cell line authentication can result in the use of contaminated or misidentified cell lines, potentially affecting the results from research and diagnostic activities. Cell line authentication and contamination detection based on metagenomic high-throughput sequencing (HTS) was tested on DNA and RNA from 63 cell lines available at the Canadian Food Inspection Agency’s National Centre for Foreign Animal Disease. Through sequence comparison of the cytochrome c oxidase subunit 1 (COX1) gene, the species identity of 53 cell lines was confirmed, and eight cell lines were found to show a greater pairwise nucleotide identity in the COX1 sequence of a different species within the same expected genus. Two cell lines, LFBK-αvβ6 and SCP-HS, were determined to be composed of cells from a different species and genus. Mycoplasma contamination was not detected in any cell lines. However, several expected and unexpected viral sequences were detected, including part of the classical swine fever virus genome in the IB-RS-2 Clone D10 cell line. Metagenomics-based HTS is a useful laboratory QA tool for cell line authentication and contamination detection that should be conducted regularly.

• HEp-2 [HeLa] cells
• HeLa
• Intestine 407 [HeLa] cells
• literature survey
• misidentified cell lines

• STR
• cell line authentication
• cross-contamination

• caries
• clinical studies
• endodontology
• nanotechnology
• oral cancer
• oral diseases
• oral medicine
• periodontology
• polymeric nanoparticles
• pre-clinical models
• restorative dentistry

• Animals
• Humans
• Mouth Diseases
• Nanoparticles/chemistry
• Nanotechnology/methods
• Polymers/chemistry

• 850936 European Research Council
• 2019-4278 Fondazione Cariplo

• Anticarcinogenic activity
• Biogenesis
• Enantioselective synthesis
• Indole alkaloids
• Isolation
• Total synthesis

• 3A (tPA-30-1)
• 3Asub E
• Cell biology
• Cell culture
• Cell lines
• Clinical research
• Obstetrics and gynecology
• Placenta
• Pregnancy
• Women's health

Gliomas are common intracranial tumors, of which 70% are malignant gliomas. Glioblastoma multiforme (GBM) is the most aggressive tumor, and patients with GBM have a median survival time of only 9–12 months; extracranial recurrence of GBM is very rare. A therapeutic strategy for this kind of recurrent tumor is lacking.

We present a case of a patient with extracranial recurrence of subscalp GBM. The subscalp tumor was resected and xenotransplanted into BALB/C nude mice. Then, glioma cells were isolated from the xenograft models and passaged in vitro. HE staining, immunohistochemistry, CCK-8 assays, karyotypic analysis, short tandem repeat STR analysis and flow cytometry were used to analyze the biological characteristics and malignant phenotype of these established cells. The cells and xenografts were then used as preclinical models to evaluate the antitumor efficacy of oncolytic herpes simplex virus 1 (oHSV-1).

The isolated cells, which were named BT-01, were positive for Nestin and GFAP. The main characteristics of BT-01 cells were that they harbored glioblastoma stem-like cells (GSCs) and that they possessed highly aggressive migration capacities compared with the existing cell lines U87-MG and U251-MG. Moreover, BT-01 cells tolerated the chemotherapeutic drug temozolomide. Our study showed that oHSV-1 could replicate in and repress the growth of BT-01 cells and significantly inhibit tumor growth in xenograft models.

Taken together, our results showed that a new recurrent glioblastoma cell line was established, which can be useful for research on recurrent glioblastoma. We provided a reliable preclinical model to evaluate the antitumor efficacy of oHSV-1 in vivo and a promising therapy for recurrent GBM.

• BT-01 cells
• glioblastoma stem-like cells
• oncolytic herpes simplex virus 1
• patient-derived xenograft
• recurrent glioblastoma

Colorectal cancer (CRC) is a challenging disease, with a high mortality rate and limited effective treatment options, particularly for late-stage disease. Patient-derived xenografts (PDXs) have emerged as an informative, renewable experimental resource to model CRC architecture and biology. Here, we describe the generation of a biobank of CRC PDXs from stage I to stage IV patients. We demonstrate that PDXs within our biobank recapitulate the histopathological and mutation features of the original patient tumor. In addition, we demonstrate the utility of this resource in pre-clinical chemotherapy and targeted treatment studies, highlighting the translational potential of PDX models in the identification of new therapies that will improve the overall survival of CRC patients.

• chemotherapy
• colon cancer
• model
• patient-derived
• xenograft

A variety of microscopy techniques are used by researchers in the life and biomedical sciences. As these techniques become more powerful and more complex, it is vital that scientific articles containing images obtained with advanced microscopes include full details about how each image was obtained. To explore the reporting of such details we examined 240 original research articles published in eight journals. We found that the quality of reporting was poor, with some articles containing no information about how images were obtained, and many articles lacking important basic details. Efforts by researchers, funding agencies, journals, equipment manufacturers and staff at shared imaging facilities are required to improve the reporting of experiments that rely on microscopy techniques.

• cell biology
• developmental biology
• imaging
• microscopy
• none
• reporting standards
• reproducibility
• science forum

• Cell Line, Tumor
• Epigenomics
• Gene Expression Profiling
• Mutation
• Neoplasms/genetics
• Transcriptome

• H2020 European Research Council

• RNA-Seq
• cell line authentication
• gene expression profiles
• human cancer cell lines
• microarray

• Cell Line, Tumor
• Gene Expression Profiling
• Humans
• Internet
• Neoplasms/genetics
• Neoplasms/pathology
• Reproducibility of Results
• Sequence Analysis, RNA/methods

• Mycoplasma
• cell culture
• contamination
• quality control
• reproducibility

• Cell Culture Techniques/methods
• Cell Line, Tumor
• Humans
• Microsatellite Repeats/genetics
• Mycoplasma/isolation & purification
• Mycoplasma/pathogenicity
• National Center for Advancing Translational Sciences (U.S.)
• Polymerase Chain Reaction
• Quality Control
• Translational Research, Biomedical/standards
• Translational Research, Biomedical/trends
• United States/epidemiology

• ZIA TR000346 Intramural NIH HHS

• IL-8
• NF-κB
• chromatin topology
• interleukin-1
• tumor necrosis factor-α

• Binding Sites
• Cells, Cultured
• Chemokines/metabolism
• Chromatin/chemistry
• Chromatin/genetics
• Chromatin/metabolism
• Enhancer Elements, Genetic/genetics
• Gene Expression Regulation/drug effects
• HeLa Cells
• Humans
• Inflammation Mediators/metabolism
• Interleukin-1alpha/pharmacology
• MAP Kinase Kinase Kinases/genetics
• MAP Kinase Kinase Kinases/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Signal Transduction
• Tumor Necrosis Factor-alpha/pharmacology

• 162103480 Deutsche Forschungsgemeinschaſt (DFG)
• 284237345 Deutsche Forschungsgemeinschaſt (DFG)
• 183582903 Deutsche Forschungsgemeinschaſt (DFG)
• 268555672 Deutsche Forschungsgemeinschaſt (DFG)
• 197785619 Deutsche Forschungsgemeinschaſt (DFG)
• 162103480 Deutsche Forschungsgemeinschaſt (DFG)
• 183582903 Deutsche Forschungsgemeinschaſt (DFG)
• 197785619 Deutsche Forschungsgemeinschaſt (DFG)
• 285697699 Deutsche Forschungsgemeinschaſt (DFG)
• 290613333 Deutsche Forschungsgemeinschaſt (DFG)
• 24676099 Deutsche Forschungsgemeinschaſt (DFG)
• 390649896 Deutsche Forschungsgemeinschaſt (DFG)
• 111447 Deutsche Krebshilfe
• Max-Planck Society
• 24676099 Excellence Cluster Cardio-Pulmonary System and Cardio-Pulmonary Institute (EXC 147: Kardiopulmonales System)
• 390649896 Cardio-Pulmonary Institute (CPI)
• DZL/UGMLC Program
• Center for Molecular Medicine Cologne (ZMMK)
• Deutsche Forschungsgemeinschaſt (DFG)
• Deutsche Krebshilfe
• Max‐Planck Society

• cancer and cancer drugs
• cell-based assays
• cytotoxicity
• profiling
• ultra-high-throughput screening

• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Cell Culture Techniques
• Cell Line
• Computational Biology/methods
• Drug Discovery/methods
• Drug Screening Assays, Antitumor/methods
• Gene Expression
• Genes, Reporter
• High-Throughput Screening Assays/methods
• Humans
• Small Molecule Libraries

• Z99 TR999999 Intramural NIH HHS

The use of cell lines in research can be affected by cell line misidentification. Short tandem repeat (STR) analysis is an effective method, and the gold standard, for the identification of the genetic origin of a cell line, but methods that allow the discrimination between cell lines of the same genetic origin are lacking. Here, we use intact cell MALDI-ToF mass spectrometry analysis, routinely used for the identification of bacteria in clinical diagnostic procedures, for the authentication of a set of cell lines consisting of three parental neuroblastoma cell lines (IMR-5, IMR-32 and UKF-NB-3) and eleven drug-adapted sublines. Principal component analysis (PCA) of intact-cell MALDI-ToF mass spectrometry data revealed clear differences between most, but not all, of the investigated cell lines. Mass spectrometry whole-cell fingerprints enabled the separation of IMR-32 and its clonal subline IMR-5. Sublines that had been adapted to closely related drugs, for example, the cisplatin- and oxaliplatin-resistant UKF-NB-3 sublines and the vincristine- and vinblastine-adapted IMR-5 sublines, also displayed clearly distinctive patterns. In conclusion, intact whole-cell MALDI-ToF mass spectrometry has the potential to be further developed into an authentication method for mammalian cells of a common genetic origin.

• authentication
• cancer
• cell line
• isogenic
• mass spectrometry

• Animals
• Antineoplastic Agents/pharmacology
• Cell Line Authentication/methods
• Cell Line, Tumor
• Cisplatin/pharmacology
• Humans
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
• Vincristine/pharmacology

• BB/K017640/1 Biotechnology and Biological Sciences Research Council

Marine sponge-derived manoalide has a potent anti-inflammatory effect, but its potential application as an anti-cancer drug has not yet been extensively investigated. The purpose of this study is to evaluate the antiproliferative effects of manoalide on oral cancer cells. MTS assay at 24 h showed that manoalide inhibited the proliferation of six types of oral cancer cell lines (SCC9, HSC3, OC2, OECM-1, Ca9-22, and CAL 27) but did not affect the proliferation of normal oral cell line (human gingival fibroblasts (HGF-1)). Manoalide also inhibits the ATP production from 3D sphere formation of Ca9-22 and CAL 27 cells. Mechanically, manoalide induces subG1 accumulation in oral cancer cells. Manoalide also induces more annexin V expression in oral cancer Ca9-22 and CAL 27 cells than that of HGF-1 cells. Manoalide induces activation of caspase 3 (Cas 3), which is a hallmark of apoptosis in oral cancer cells, Ca9-22 and CAL 27. Inhibitors of Cas 8 and Cas 9 suppress manoalide-induced Cas 3 activation. Manoalide induces higher reactive oxygen species (ROS) productions in Ca9-22 and CAL 27 cells than in HGF-1 cells. This oxidative stress induction by manoalide is further supported by mitochondrial superoxide (MitoSOX) production and mitochondrial membrane potential (MitoMP) destruction in oral cancer cells. Subsequently, manoalide-induced oxidative stress leads to DNA damages, such as γH2AX and 8-oxo-2’-deoxyguanosine (8-oxodG), in oral cancer cells. Effects, such as enhanced antiproliferation, apoptosis, oxidative stress, and DNA damage, in manoalide-treated oral cancer cells were suppressed by inhibitors of oxidative stress or apoptosis, or both, such as N-acetylcysteine (NAC) and Z-VAD-FMK (Z-VAD). Moreover, mitochondria-targeted superoxide inhibitor MitoTEMPO suppresses manoalide-induced MitoSOX generation and γH2AX/8-oxodG DNA damages. This study validates the preferential antiproliferation effect of manoalide and explores the oxidative stress-dependent mechanisms in anti-oral cancer treatment.

• anticancer drug
• marine sponge
• natural product
• oral cancer inhibition

• AMD
• Electron tomography
• Fibrillar centers
• Mitotic NORs
• Nucleolar caps
• UBTF1/2
• rDNA

• bias
• data reliability
• meta-research
• publication bias
• replication crisis
• reproducibility crisis

• Humans
• Reproducibility of Results
• Research Personnel/standards

The use of misidentified and contaminated cell lines continues to be a problem in biomedical research. Research Resource Identifiers (RRIDs) should reduce the prevalence of misidentified and contaminated cell lines in the literature by alerting researchers to cell lines that are on the list of problematic cell lines, which is maintained by the International Cell Line Authentication Committee (ICLAC) and the Cellosaurus database. To test this assertion, we text-mined the methods sections of about two million papers in PubMed Central, identifying 305,161 unique cell-line names in 150,459 articles. We estimate that 8.6% of these cell lines were on the list of problematic cell lines, whereas only 3.3% of the cell lines in the 634 papers that included RRIDs were on the problematic list. This suggests that the use of RRIDs is associated with a lower reported use of problematic cell lines.

• authentication
• cell line
• computational biology
• none
• reproducibility
• rigor
• software
• systems biology
• text mining

While problems with cell line misidentification have been known for decades, an unknown number of published papers remains in circulation reporting on the wrong cells without warning or correction. Here we attempt to make a conservative estimate of this ‘contaminated’ literature. We found 32,755 articles reporting on research with misidentified cells, in turn cited by an estimated half a million other papers. The contamination of the literature is not decreasing over time and is anything but restricted to countries in the periphery of global science. The decades-old and often contentious attempts to stop misidentification of cell lines have proven to be insufficient. The contamination of the literature calls for a fair and reasonable notification system, warning users and readers to interpret these papers with appropriate care.

• Biomedical Research/methods
• Biomedical Research/standards
• Cell Line/classification
• HeLa Cells
• Humans
• Periodicals as Topic
• Research/standards

• Horizon 2020 Framework Programme