ScienceDirect Publication: Pathology - Research and Practice
- Hobnail cells in encapsulated papillary thyroid carcinoma: Report of 2 cases with immunohistochemical and molecular findings and literature analysisPublication date: Available online 30 September 2019Source: Pathology - Research and PracticeAuthor(s): Shweta Agarwal, Qandeel Sadiq, Ibrahim OrtancaAbstractPapillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland with most tumors behaving in an indolent fashion. However, morphologic variants have been described, such as tall cell, diffuse sclerosing, columnar cell etc. which are biologically more aggressive. One
- Acoustic Voice Quality Index as a Potential Tool for Voice ScreeningPublication date: Available online 30 September 2019Source: Journal of VoiceAuthor(s): Maryam Faham, Anne-Maria Laukkanen, Tero Ikävalko, Leena Rantala, Ahmed Geneid, Sofia Holmqvist-Jämsén, Kaarina Ruusuvirta, Sirpa PiriläAbstractIntroductionTo diminish the risk of voice disorders in people who are highly dependent on their voices, such as teachers, vocal screening is important already at the beginning of such individuals’ professional studies.
Oral Diseases
- Cover ImageCover image © Qian Liu and Meiqing Wang Images The cover image is based on the Original Article Bilateral anterior elevation prosthesis boosts chondrocytes proliferation in mice mandibular condyle by Qian Liu et al., https://doi.org/10.1111/odi.13128.
- Might smoking assuage the pro‐inflammatory effect of diabetes in periodontal sites?Abstract Objectives This study evaluated the effects of type 2 diabetes mellitus (DM), smoking and these two factors combined on gingival crevicular fluid levels and ratios of pro‐/anti‐inflammatory cytokines. Associations between cytokines with each other and with key periodontal pathogens in periodontal sites under the challenge of one or both of these risk factors were also assessed. Methods 102 subjects with periodontitis were inclu
Molecular Cancer Therapeutics Online First Articles
- Molecular Inhibitor of QSOX1 Suppresses Tumor Growth in vivoQuiescin Sulfhydryl Oxidase 1 (QSOX1) is an enzyme overexpressed by many different tumor types. QSOX1 catalyzes the formation of disulfide bonds in proteins. Since short hairpin knockdowns of QSOX1 have been shown to suppress tumor growth and invasion in vitro and in vivo, we hypothesized that chemical compounds inhibiting QSOX1 enzymatic activity would also suppress tumor growth, invasion, and metastasis. High throughput screening using a QSOX1-
- Targeting Histone Chaperone FACT Complex Overcomes 5-Fluorouracil Resistance in Colon CancerFluorouracil (5-FU) remains a first-line chemotherapeutic agent for colorectal cancer (CRC). However, a subset of CRC patients who have defective mismatch repair (dMMR) pathway show resistance to 5-FU. Here, we demonstrate that the efficacy of 5-FU in dMMR CRC cells is largely dependent on the DNA base excision repair (BER) pathway. Downregulation of APE1, a key enzyme in BER pathway, decreases IC50 of 5-FU in dMMR CRC cells by 10-fold. Furthermo
- Pralatrexate in combination with oxaliplatin in advanced esophago-gastric cancer: a phase II trial with predictive molecular correlatesThe purpose of our study was to evaluate the efficacy of a combination of pralatrexate plus oxaliplatin in advanced Esophago-Gastric cancer (EGC), analyze the impact of polymorphisms in folate metabolism pathway genes on toxicity and efficacy of pralatrexate and to evaluate microRNA profile of tumor epithelium as a predictive biomarker. This was a two-stage trial with a safety lead in cohort and a primary endpoint of overall response rate (ORR).
- Amplification of the mutation-carrying BRCA2 allele promotes RAD51 loading and PARP inhibitor resistance in the absence of reversion mutations.Patients harboring germline Breast Cancer susceptibility genes 1 and 2 (BRCA1/2) mutations are predisposed to developing breast, pancreatic, and ovarian cancers. BRCA2 plays a critical role in homologous recombination DNA repair and deleterious mutations in BRCA2 confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition. Recently, the PARP inhibitors olaparib and rucaparib were FDA approved for the treatment of metastatic breast cancer
Applied and Environmental Microbiology Evolutionary and Genomic Microbiology
- Independent Evolution with the Gene Flux Originating from Multiple Xanthomonas Species Explains Genomic Heterogeneity in Xanthomonas perforans [Evolutionary and Genomic Microbiology]Xanthomonas perforans is the predominant pathogen responsible for bacterial leaf spot of tomato and X. euvesicatoria for that of pepper in the southeast United States. Previous studies have indicated significant changes in the X. perforans population collected from Florida tomato fields over the span of 2 decades, including a shift in race and diversification into three phylogenetic groups driven by genome-wide homologous-recombination events der
Evolutionary Biology News -- ScienceDaily
- 250-million-year-old evolutionary remnants seen in muscles of human embryosA team of evolutionary biologists have demonstrated that some limb muscles known to be present in many mammals but absent in the adult human are actually formed during early human development and then lost prior to birth. These findings offer insight into how our arms and legs evolved from our mammalian ancestors, and also help explain rare limb anomalies found in humans born with congenital malformations.
- Climate change could pit species against one another as they shift rangesSpecies have few good options when it comes to surviving climate change -- they can genetically adapt to new conditions, shift their ranges, or both. But new research indicates that conflicts between species as they adapt and shift ranges could lead experts to underestimate extinctions, and underscores the importance of landscape connectivity.
- Pineapple genome sequences hint at plant domestication in a single stepAn international team published their analysis of the genome of the red pineapple, a plant grown for fiber production and as an ornamental.
Clinical Cancer Research Online First Articles
- Identification of FES as a novel radiosensitizing target in human cancersPurpose: The identification of novel targets for developing synergistic drug-radiation combinations would pave the way to overcome tumor radioresistance. We conducted cell-based screening of a human kinome siRNA library to identify a radiation-specific kinase that has a synergistic toxic effect with radiation upon inhibition and is not essential for cell survival in the absence of radiation. Experimental Design: Unbiased RNAi screening was perfo
- ARID5B influences anti-metabolite drug sensitivity and prognosis of acute lymphoblastic leukemiaPurpose: Treatment outcomes for childhood acute lymphoblastic leukemia (ALL) have improved steadily, but a significant proportion of patients still experience relapse due to drug resistance, which is partly explained by inherited and/or somatic genetic alternations. Recently, we and others have identified genetic variants in the ARID5B gene associated with susceptibility to ALL and also with relapse. In this study, we sought to characterize the m
- An Integrative Approach to Inform Optimal Administration of OX40 Agonist Antibodies in Patients with Advanced Solid TumorsPurpose:The success of checkpoint blockade has led to a significant increase in the development of a broad range of immunomodulatory molecules for the treatment of cancer, including agonists against T-cell costimulatory receptors, such as OX40. Unlike checkpoint blockade, where complete and sustained receptor saturation may be required for maximal activity, the optimal dosing regimen and receptor occupancy for agonist agents is less well understo
- Quality assessment of cryopreserved biospecimens reveals presence of intact biomoleculesAbstract Recapitulation of tumor features in isolated biomolecules is preeminently dependent on obtaining reliable quality biospecimen. Moreover, quality assessment of bio banked specimens at regular intervals is an essential intervention for carrying out effective translational and clinical research. In the current study, genomic DNA was extracted from 140 fresh frozen tissues of oral, breast and colorectal specimens cryopreserved over a period
- Two‐ and three‐photon absorption cross‐section characterization for high‐brightness, cell‐specific multiphoton fluorescence brain imagingWe demonstrate an accurate quantitative characterization of absolute two‐ and three‐photon absorption (2PA and 3PA) action cross sections of a genetically encodable fluorescent marker Sypher3s. Both 2PA and 3PA action cross sections of this marker are found to be remarkably high, enabling high‐brightness, cell‐specific two‐ and three‐photon fluorescence brain imaging. Brain imaging experiments on sliced samples of rat's cortical areas are present
- Photobiomodulation Therapy in Knee Osteoarthritis Reduces Oxidative Stress and Inflammatory Cytokines in RatsAbstract Knee osteoarthritis (OA) is a chronic disease that causes pain and gradual degeneration of the articular cartilage. In this study, MIA‐induced OA knee model was used in rats to test the effects of the photobiomodulation therapy (PBM). We analyzed the inflammatory process (pain and cytokine levels), and its influence on the oxidative stress and antioxidant capacity. Knee OA was induced by monosodium iodoacetate (MIA) intra‐articular inje
- Interplay of temperature, thermal‐stresses and strains in laser‐assisted modification of collagenous tissues: speckle‐contrast and OCT‐based studiesModerate heating of collagenous tissues such as cartilage and cornea by infrared laser irradiation can produce biologically non‐destructive structural rearrangements and relaxation of internal stresses resulting in the tissue reshaping. The reshaping results and eventual changes in optical and biological properties of the tissue strongly depend on the laser‐irradiation regime. Here, a speckle‐contrast technique based on monochromatic illumination
- Spectral characteristics of caries autofluorescence obtained from different locations and caries severitiesAbstract Dental caries usually occurs at interproximal and occlusal surfaces. The purpose of the present study was to determine if characteristic spectral factors extracted from autofluorescence (AF) spectra are informative regarding caries detection and the determination of caries stage as compared with DIAGNOdent results. AF spectra were obtained from caries lesions of different severities at two locations using a 405 nm laser. Three spectral
- Pathogenic role of exosomes and microRNAs in HPV‐mediated inflammation and cervical cancer: A reviewCervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well‐controlled, however, if the inflammati
- Specific RITA Modification Produces Hyperselective Cytotoxicity While Maintaining In Vivo Antitumor EfficacyThe preclinical antitumor agent RITA (2,5-bis[5-hydroxymethyl-2-thienyl] furan, NSC 652287), an analog of the natural product α-terthiophene, failed during the development phase due to acute pulmonary toxicity in animal models. A series of synthetic modifications to RITA's heterocyclic scaffold resulted in activity ranging from broadly cytotoxic to highly selective. In the NCI 60-cell line screen, these "hyperselective" agents (e.g., imatinib) ar
- Tyrosine Threonine Kinase Inhibition Eliminates Lung Cancers by Augmenting Apoptosis and PolyploidyThe spindle assembly checkpoint maintains genomic integrity. A key component is tyrosine threonine kinase (TTK, also known as Mps1). TTK antagonism is hypothesized to cause genomic instability and cell death. Interrogating The Cancer Genome Atlas revealed high TTK expression in lung adenocarcinomas and squamous cell cancers versus the normal lung (P < 0.001). This correlated with an unfavorable prognosis in examined lung adenocarcinoma cases (P =
- AKR1C3 Promotes AR-V7 Protein Stabilization and Confers Resistance to AR-Targeted Therapies in Advanced Prostate CancerThe mechanisms resulting in resistance to next-generation antiandrogens in castration-resistant prostate cancer are incompletely understood. Numerous studies have determined that constitutively active androgen receptor (AR) signaling or full-length AR bypass mechanisms may contribute to the resistance. Previous studies established that AKR1C3 and AR-V7 play important roles in enzalutamide and abiraterone resistance. In the present study, we found
- Receptor Tyrosine Kinase Signaling Networks Define Sensitivity to ERBB Inhibition and Stratify Kras-Mutant Lung CancersMost non–small cell lung cancers (NSCLC) contain nontargetable mutations, including KRAS, TP53, or STK11/LKB1 alterations. By coupling ex vivo drug sensitivity profiling with in vivo drug response studies, we aimed to identify drug vulnerabilities for these NSCLC subtypes. Primary adenosquamous carcinoma (ASC) or adenocarcinoma (AC) cultures were established from KrasG12D/+;Lkb1fl/fl (KL) tumors or AC cultures from KrasG12D/+;p53fl/fl (KP) tumors
- Mechanisms of NT5C2-Mediated Thiopurine Resistance in Acute Lymphoblastic LeukemiaRelapse remains a formidable challenge for acute lymphoblastic leukemia (ALL). Recently, recurrent mutations in NT5C2 were identified as a common genomic lesion unique in relapsed ALL and were linked to acquired thiopurine resistance. However, molecular mechanisms by which NT5C2 regulates thiopurine cytotoxicity were incompletely understood. To this end, we sought to comprehensively characterize the biochemical and cellular effects of NT5C2 mutat
- Serum PD-1 Is Elevated after Pembrolizumab Treatment but Has No Predictive ValueImmune-checkpoint blockade (ICB) uses antibody targeting of specific inhibitory receptors and ligands. The major limitations of ICB, such as high cost, limited success rate, and immune-related adverse events (irAE), highlight the need for predictive biomarkers. We analyzed pre-immunotherapy and post-immunotherapy serum samples of 24 patients treated with pembrolizumab for changes in PD-1 and over 1,000 additional protein markers using a multiplex
- Preclinical Development of U3-1784, a Novel FGFR4 Antibody Against Cancer, and Avoidance of Its On-target ToxicityThe FGFR4/FGF19 signaling axis is overactivated in 20% of liver tumors and currently represents a promising targetable signaling mechanism in this cancer type. However, blocking FGFR4 or FGF19 has proven challenging due to its physiological role in suppressing bile acid synthesis which leads to increased toxic bile acid plasma levels upon FGFR4 inhibition. An FGFR4-targeting antibody, U3-1784, was generated in order to investigate its suitability
- Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Colorectal Cancer: Implications for Response and Resistance to Targeted TherapeuticsMolecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool. Here, next-generation sequencing (NGS) of blood-derived ctDNA was performed in patients with advanced colorectal cancer. We investigated ctDNA-derived genomic alterations, including potential actionability, concordance with tissue NGS, and serial dynamics in 78 patients with colorectal cancer using a clinical-grade NGS assay that detects single nucleotide varian
- A Novel Therapeutic Induces DEPTOR Degradation in Multiple Myeloma Cells with Resulting Tumor CytotoxicityPrior work indicates DEPTOR expression in multiple myeloma cells could be a therapeutic target. DEPTOR binds to mTOR via its PDZ domain and inhibits mTOR kinase activity. We previously identified a drug, which prevented mTOR–DEPTOR binding (NSC126405) and induced multiple myeloma cytotoxicity. We now report on a related therapeutic, drug 3g, which induces proteasomal degradation of DEPTOR. DEPTOR degradation followed drug 3g binding to its PDZ do
- Co-targeting Bulk Tumor and CSCs in Clinically Translatable TNBC Patient-Derived Xenografts via Combination NanotherapyTriple-negative breast cancer (TNBC) accounts disproportionally for the majority of breast cancer–related deaths throughout the world. This is largely attributed to lack of a specific therapy capable of targeting both bulk tumor mass and cancer stem cells (CSC), as well as appropriate animal models to accurately evaluate treatment efficacy for clinical translation. Thus, development of effective and clinically translatable targeted therapies for
- Leelamine Is a Novel Lipogenesis Inhibitor in Prostate Cancer Cells In Vitro and In VivoIncreased de novo synthesis of fatty acids is implicated in the pathogenesis of human prostate cancer, but a safe and effective clinical inhibitor of this metabolic pathway is still lacking. We have shown previously that leelamine (LLM) suppresses transcriptional activity of androgen receptor, which is known to regulate fatty acid synthesis. Therefore, the current study was designed to investigate the effect of LLM on fatty acid synthesis. Exposu
- GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ExpressionHormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. Degarelix (Firmagon), a gonadotropin-releasing hormone (GnRH) receptor antagonist differs from luteinizing hormone-releasing hormone (LHRH) agonists by avoiding "testosterone flare" and lower follicle-stimulating hormone (FSH) levels. The direct effect of degarelix and leuprolide on human prostate cancer cells was evaluated. In LNCaP, C
- Novel Pyrrolo[3,2-d]pyrimidine Compounds Target Mitochondrial and Cytosolic One-carbon Metabolism with Broad-spectrum Antitumor EfficacyFolate-dependent one-carbon (C1) metabolism is compartmentalized into the mitochondria and cytosol and supports cell growth through nucleotide and amino acid biosynthesis. Mitochondrial C1 metabolism, including serine hydroxymethyltransferase (SHMT) 2, provides glycine, NAD(P)H, ATP, and C1 units for cytosolic biosynthetic reactions, and is implicated in the oncogenic phenotype across a wide range of cancers. Whereas multitargeted inhibitors of c
- A Novel Anti-HER2 Antibody-Drug Conjugate XMT-1522 for HER2-Positive Breast and Gastric Cancers Resistant to Trastuzumab EmtansineMost patients with HER2-positive breast or gastric cancer exhibit primary or acquired resistance to trastuzumab emtansine (T-DM1), and such patients may have limited therapeutic options. XMT-1522 is a novel anti-HER2 antibody–drug conjugate. We compared XMT-1522 to T-DM1 in preclinical models. The effects of XMT-1522 and T-DM1 on cell survival and apoptosis were compared in six HER2-positive breast cancer or gastric cancer cell lines, of which th
- Targeting MUC1-C Inhibits TWIST1 Signaling in Triple-Negative Breast CancerThe oncogenic MUC1-C protein and the TWIST1 epithelial–mesenchymal transition transcription factor (EMT-TF) are aberrantly expressed in triple-negative breast cancer (TNBC) cells. However, there is no known association between MUC1-C and TWIST1 in TNBC or other cancer cells. Here, we show that MUC1-C activates STAT3, and that MUC1-C and pSTAT3 drive induction of the TWIST1 gene. In turn, MUC1-C binds directly to TWIST1, and MUC1-C/TWIST1 complexe
- Altered Steroid Milieu in AI-Resistant Breast Cancer Facilitates AR Mediated Gene-Expression Associated with Poor Response to TherapyDivergent roles for androgen receptor (AR) in breast cancer have been reported. Following aromatase inhibitor (AI) treatment, the conversion of circulating androgens into estrogens can be diminished by >99%. We wished to establish whether the steroid environment can dictate the role of AR and the implications of this for subsequent therapy. This study utilizes models of AI resistance to explore responsiveness to PI3K/mTOR and anti-AR therapy when
- Suppression of Nuclear Factor-{kappa}B by Glucocorticoid Receptor Blocks Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer CellsOur clinically relevant finding is that glucocorticoids block estrogen (E2)-induced apoptosis in long-term E2-deprived (LTED) breast cancer cells. However, the mechanism remains unclear. Here, we demonstrated that E2 widely activated adipose inflammatory factors such as fatty acid desaturase 1 (FADS1), IL6, and TNFα in LTED breast cancer cells. Activation of glucocorticoid receptor (GR) by the synthetic glucocorticoid dexamethasone upregulated FA
- Atovaquone: An Antiprotozoal Drug Suppresses Primary and Resistant Breast Tumor Growth by Inhibiting HER2/{beta}-Catenin SignalingBreast cancer is the second leading cause of cancer-related mortality in women. In the current study, we evaluated the anticancer effects of an antiprotozoal drug, atovaquone, against several breast cancer cell lines. Our results showed that atovaquone treatment induced apoptosis and inhibited the growth of all the breast cancer cell lines tested, including several patient-derived cells. In addition, atovaquone treatment significantly reduced the
- High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast CancersBOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly checkpoint activity. BOS172722 synergizes with paclitaxel to induce gross chromosomal segregation defects caused by MPS1 inhibitor
- Metabolic Flexibility in Cancer: Targeting the Pyruvate Dehydrogenase Kinase:Pyruvate Dehydrogenase AxisCancer cells use alterations of normal metabolic processes to sustain proliferation indefinitely. Transcriptional and posttranscriptional control of the pyruvate dehydrogenase kinase (PDK) family is one way in which cancer cells alter normal pyruvate metabolism to fuel proliferation. PDKs can phosphorylate and inactivate the pyruvate dehydrogenase complex (PDHC), which blocks oxidative metabolism of pyruvate by the mitochondria. This process is t
- Zınc Fınger Proteın 703 ıs an ımportant player ın head and neck cancerAbstract Objectives Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) remains difficult to treat and the overall survival rate has only modestly improved over the past years. Therefore, there is a need to understand the molecular mechanism of HNSCC. Zinc Finger Protein 703 (ZNF703) is an oncogenic transcription factor and ZNF703 gene expression is altered in many cancers as a result of Chromosome 8p12 amplification.
- “M” line: new anatomical landmark for the maxillary sinus natural ostiumAbstract Objective Describe a reliable anatomical landmark that can be used to locate the maxillary sinus natural ostium (MSNO) during endoscopic surgery, even if the uncinate process is preserved. Design Descriptive anatomical. Setting An anatomical and radiological study was performed to evaluate the consistency of the landmark, denominated "M" line. Subjects and Methods Dissections were performed in 57 cadaver heads (114
- The microbiology of ear cultures in a high‐burden setting in tropical Australia; implications for cliniciansAbstract 1.In tropical Australia, the burden of ear infections is disproportionately borne by Indigenous Australians and those living in rural and remote locations. 2. Despite this study’s tropical setting, the pathogens identified were similar to those seen in temperate climates, with Pseudomonas aeruginosa and Staphylococcus aureus, the most common isolates. 3. Antimicrobial resistance in Far North Queensland is increasing and ongoing survei
- Nerve‐tumor interaction enhances the aggressiveness of oral squamous cell carcinomaAbstract Objectives Perineural invasion (PNI) is a poor prognostic pathologic feature of oral squamous cell carcinoma (OSCC). The mechanisms of PNI remain poorly understood, and nerve‐tumor interactions have been implicated for its pathogenesis. Design and setting Systematic investigation of nerve‐tumor interactions was performed using fresh human peripheral nerve. In vitro and in vivo models were used to determine the ability of human
- Prognostic role of pretreatment serum albumin in patients with nasopharyngeal carcinoma: a meta‐analysis and systematic reviewAbstract Background Pretreatment serum albumin (ALB) is a novel index that was identified in recent years and is considered to be closely related to the prognosis of nasopharyngeal carcinoma (NPC). However, the association between ALB and NPC remains controversial. Objective of Review To assess the prognostic significance of pretreatment serum ALB in patients with NPC. Type of Review A systematic review and meta‐analysis. Sea
- Continuous versus intermittent intraoperative neuromonitoring in complex benign thyroid surgery: A retrospective analysis and prospective follow‐upAbstract Objectives To compare continuous (C‐IONM) versus intermittent intraoperative neuromonitoring (I‐IONM) in complex benign thyroid surgery, and to follow‐up patients with loss of signal (LOS) or unilateral vocal fold paralysis (UVFP). Design Retrospective clinical study, prospective case series. Setting University hospital and academic teaching hospital of Charité ‐ University Medicine Berlin, Germany. Participants C‐I
Τρίτη 1 Οκτωβρίου 2019
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