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Toxicol Lett 2021 Apr 16. Epub 2021 Apr 16.

State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou medical university, No. 151 Yanjiang Road, Yuexiu District, Guangzhou 510120, China; The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, China. Electronic address:

Tobacco exposure is well known to induce genetic and epigenetic changes that contribute to the pathogenesis of lung cancer. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a significant tobacco-specific carcinogen, but the oncogenic mechanisms of NNK have not been thoroughly elucidated. In this study we found that DNA methyltransferase 1(DNMT1) was overexpressed in malignantly transformed human bronchial epithelial Beas-2B cells induced by NNK (2B-NNK cells), by treatment with NNK (400 μg/ml) for 7 days. Read More

Front Oncol 2021 31;11:659049. Epub 2021 Mar 31.

Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA, United States.

Cellular homeostasis is governed by the precise expression of genes that control the translation, localization, and termination of proteins. Oftentimes, environmental and biological factors can introduce mutations into the genetic framework of cells during their growth and division, and these genetic abnormalities can result in malignant transformations caused by protein malfunction. For example, p53 is a prominent tumor suppressor protein that is capable of undergoing more than 300 posttranslational modifications (PTMs) and is involved with controlling apoptotic signaling, transcription, and the DNA damage response (DDR). Read More

Drug Resist Updat 2021 Mar 19;56:100762. Epub 2021 Mar 19.

The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel. Electronic address:

Prostate cancer (PC) is the second most common cause of death amongst men in the USA. Therapy of PC has been transformed in the past decade by introducing novel therapeutics, advanced functional imaging and diagnostic approaches, next generation sequencing, as well as improved application of existing therapies in localized PC. Treatment of PC at the different stages of the disease may include surgery, androgen deprivation therapy (ADT), chemotherapy and radiation therapy. Read More

Cancer Cell 2021 Mar 30. Epub 2021 Mar 30.

The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. Electronic address:

Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. Read More

J Oncol 2021 25;2021:5512524. Epub 2021 Mar 25.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Read More

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Institute for Hematopathology, Fangdieckstr. 75, 22547 Hamburg, Germany.

Extracellular vesicles (EVs) serve as trafficking vehicles and intercellular communication tools. Their cargo molecules directly reflect characteristics of their parental cell. This includes information on cell identity and specific cellular conditions, ranging from normal to pathological states. Read More

Cancers (Basel) 2021 Mar 17;13(6). Epub 2021 Mar 17.

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.

Cancer genomes evolve in a punctuated manner during tumor evolution. Abrupt genome restructuring at key steps in this evolution has been called "genome chaos." To answer whether widespread genome change is truly chaotic, this review (i) summarizes the limited number of cell and molecular systems that execute genome restructuring, (ii) describes the characteristic signatures of DNA changes that result from activity of those systems, and (iii) examines two cases where genome restructuring is determined to a significant degree by cell type or viral infection. Read More

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.

The brain is a common site of metastasis from advanced breast cancer but few effective treatments are available. We examined a therapeutic option with a conditioned medium (CM), focusing on the role of Lrp5 and β-catenin in Wnt signaling, and IL1ra in osteocytes. Osteocytes presented the innate anti-tumor effect and the overexpression of the above genes strengthened their action. Read More

Asian Pac J Cancer Prev 2021 Mar 1;22(3):719-724. Epub 2021 Mar 1.

Department of Histopathology, PNS Shifa Hospital, Karachi, Pakistan.

Background: Pathogenic germline mutations in BRCA1/2 constitute the majority of hereditary breast and/or ovarian cancers worldwide. Incidence and mortality rate of breast and ovarian cancers in Pakistani women is high. Thus, to establish the diagnosis for targeted therapy in Pakistan, we conducted Next-generation sequencing-based germline testing for the detection of BRCA1/2 oncogenic variants associated with breast and ovarian cancer subtype. Read More

Ginekol Pol 2021 Mar 23. Epub 2021 Mar 23.

Department of Molecular Virology, Institute of Experimental Biology, Adam Mickiewicz University in Poznan, Poland.

One of the most intriguing problems in biomedical sciences is the theory explaining cancer formation. It is known that cancer is the result of many molecular processes, the presence of oncogenic factors and the loss of apoptosis of affected cells. We currently have hypotheses based on carcinogenesis because of a single cell gene mutation, i. Read More

Vaccine 2021 Apr 18;39(16):2255-2263. Epub 2021 Mar 18.

Agency for Care Effectiveness, Ministry of Health, Singapore. Electronic address:

Background: The nonavalent human papillomavirus (HPV) vaccine has been shown to extend protection against oncogenic HPV types 31/33/45/52/58 (HPV-OV) not covered by the bivalent and quadrivalent HPV vaccines. Besides its clinical benefit, evidence on the economic value of the nonavalent vaccine is required to inform local vaccination strategies and funding decisions. This study evaluated the cost-effectiveness of replacing the bivalent vaccine with the nonavalent vaccine in the national school-based HPV vaccination programme in Singapore. Read More

BMC Womens Health 2021 Mar 21;21(1):118. Epub 2021 Mar 21.

Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.

Background: Extragonadal endometriosis is a rare condition, and its disease manifestation and long-term prognosis have not been elucidated. We report an extragonadal endometriosis case controlled by drug therapy for 14 years with analysis of the sex hormone receptor expression and PIK3CA mutation.

Case Presentation: The patient was diagnosed with bladder endometriosis at age of 30 years, and underwent bilateral nephrostomy and GnRHa therapy with add-back therapy. Read More

Cancer Treat Rev 2021 Apr 1;95:102173. Epub 2021 Mar 1.

Sarah Cannon Research Institute / Tennessee Oncology, PLLC., 250 25th Avenue, Nashville, TN 37203, USA.

The mesenchymal-epithelial transition (MET) receptor tyrosine kinase binds the hepatocyte growth factor to activate downstream cell signaling pathways involved in cell proliferation, survival, and migration. Several genetic mechanisms can result in an aberrant activation of this receptor in cancer cells. One such activating mechanism involves the acquisition of gene mutations that cause MET exon 14 skipping (METex14) during mRNA splicing. Read More

Ophthalmic Epidemiol 2021 Mar 18:1-6. Epub 2021 Mar 18.

Department of Ophthalmology, Chaophaya Abhaibhubejhr Hospital, Prachinburi, Thailand.

: Pterygium, a common ocular growth, has an unknown pathogenesis and aetiology. Environmental factors such as ultraviolet light, genetic factors and viral infections may be implicated in the development of pterygia. Human papillomavirus (HPV), an oncogenic virus, has previous been detected in individuals with pterygia. Read More

Cancer Sci 2021 Mar 17. Epub 2021 Mar 17.

Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Cell identity is known to be controlled by regulatory elements within the genome, such as promoters, enhancers, and insulators. These regulatory elements interact with each other in the nucleus and form tissue-specific chromatin structures. Dysregulation of these elements and their interactions can lead to loss of cell identity and promote the development of diseases such as cancer. Read More

Endocr J 2021 Mar 13. Epub 2021 Mar 13.

Department of General Surgery, The Affiliated Hospital Of Guizhou Medical University, Guiyang City, Guizhou Province, China.

The circular RNA PRKCI (circ-PRKCI; ID: hsa_circ_0122683) is highly expressed in human papillary thyroid cancer (PTC) tumors according to GSE93522 dataset. However, its role in PTC tumorigenesis remains to be documented. Here, quantitative real-time PCR showed that expression of circ-PRKCI was abnormally upregulated in human PTC patients' tumors and cells, and higher circ-PRKCI might predict lymph node metastasis and recurrence. Read More

Int J Mol Sci 2021 Feb 27;22(5). Epub 2021 Feb 27.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.

Multiple myeloma (MM) is a common hematological malignancy arising from terminally differentiated plasma cells. In the majority of cases, symptomatic disease is characterized by the presence of bone disease. Multiple myeloma bone disease (MMBD) is a result of an imbalance in the bone-remodeling process that leads to increased osteoclast activity and decreased osteoblast activity. Read More

Front Mol Biosci 2020 16;7:599332. Epub 2021 Feb 16.

Department of Oncology, Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.

In mammalian cells, cell cycle entry occurs in response to the correct stimuli and is promoted by the transcriptional activity of E2F family members. E2F proteins regulate the transcription of S phase cyclins and genes required for DNA replication, DNA repair, and apoptosis. The activity of E2F1, the archetypal and most heavily studied E2F family member, is tightly controlled by the DNA damage checkpoints to modulate cell cycle progression and initiate programmed cell death, when required. Read More

Bio Protoc 2020 May 20;10(10):e3620. Epub 2020 May 20.

Institute for Cancer Genetics, Columbia University, New York, USA.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that arises from transformation of T-cell primed hematopoietic progenitors. Although T-ALL is a heterogenous and molecularly complex disease, more than 65% of T-ALL patients carry activating mutations in the gene. The majority of T-ALL-associated mutations either disrupt the negative regulatory region, allowing signal activation in the absence of ligand binding, or result in truncation of the C-terminal PEST domain involved in the termination of NOTCH1 signaling by proteasomal degradation. Read More

Cell Death Discov 2021 Mar 1;7(1):41. Epub 2021 Mar 1.

Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou road, Nanjing, Jiangsu Province, 210029, China.

Breast cancer is the leading cause of cancer-related death in women around the world. It is urgently needed to identify genes associated with tumorigenesis and prognosis, as well as to elucidate the molecular mechanisms underlying the oncogenic process. Long noncoding RNAs (lncRNAs) are widely involved in the pathological and physiological processes of organisms and play an important role as oncogenes or tumor suppressor genes, affecting the development and progression of tumors. Read More

Eur J Pharmacol 2021 May 26;898:173983. Epub 2021 Feb 26.

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Genetic and epigenetic alterations have been under concentrated investigations for many years in order to unearth the molecules regulating human cancer pathogenesis. However, the identification of a wide range of dysregulated genes and their protein products has raised a question regarding how the results of this large collection of alterations could converge into a formation of one malignancy. The answer may be found in the signaling cascades that regulate the survival and metabolism of the cells. Read More

Adv Sci (Weinh) 2021 Feb 6;8(4):2003205. Epub 2021 Jan 6.

Cancer Institute Department of Biochemistry Jiangsu Key Laboratory for Molecular and Medical Biotechnology College of Life Science Nanjing Normal University Nanjing 210023 P. R. China.

Triple negative breast cancer (TNBC), with its lack of targeted therapies, shows the worst mortality rate among all breast cancer subtypes. Clusterin (CLU) is implicated to play important oncogenic roles in cancer via promoting various downstream oncogenic pathways. Here, protein kinase D3 (PRKD3) is defined to be a key regulator of CLU in promoting TNBC tumor growth. Read More

Environ Toxicol Pharmacol 2021 Feb 20;85:103627. Epub 2021 Feb 20.

Department of Hematology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, China. Electronic address:

The aberrant micro-RNA (miR) expression has been reported to play a vital role in proliferation and tumorigenesis and of several human cancers. MicroRNA-365 (miR-365) has been shown to exhibit tumor-suppressive or oncogenic role in several human cancers. Nonetheless, little is known about its growth regulatory role in human multiple myeloma. Read More

J Biol Chem 2021 Feb 19:100445. Epub 2021 Feb 19.

Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address:

Within the AGC kinase superfamily, gene fusions resulting from chromosomal rearrangements have been most frequently described for protein kinase C (PKC), with gene fragments encoding either the C-terminal catalytic domain or the N-terminal regulatory moiety fused to other genes. Kinase fusions that eliminate regulatory domains are typically gain-of-function and often oncogenic. However, several quality control pathways prevent accumulation of aberrant PKC, suggesting that PKC fusions may paradoxically be loss-of-function. Read More

Nat Commun 2021 02 19;12(1):1176. Epub 2021 Feb 19.

NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.

The first step of RAF activation involves binding to active RAS, resulting in the recruitment of RAF to the plasma membrane. To understand the molecular details of RAS-RAF interaction, we present crystal structures of wild-type and oncogenic mutants of KRAS complexed with the RAS-binding domain (RBD) and the membrane-interacting cysteine-rich domain (CRD) from the N-terminal regulatory region of RAF1. Our structures reveal that RBD and CRD interact with each other to form one structural entity in which both RBD and CRD interact extensively with KRAS. Read More

Radiographics 2021 Mar-Apr;41(2):576-594. Epub 2021 Feb 19.

From the Department of Radiology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259.

Histiocytosis is a rare inflammatory process characterized by pathologic infiltration and accumulation of cells derived from the monocytic lineage in normal tissue. It encompasses more than 100 different subtypes of disorders that were recently classified into five main groups: Langerhans-related histiocytosis, Rosai-Dorfman histiocytosis, cutaneous and mucocutaneous histiocytosis, malignant histiocytosis, and hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Langerhans cell histiocytosis is the most common histiocytic disorder. Read More

Cell Death Dis 2021 Feb 18;12(2):194. Epub 2021 Feb 18.

Center of Toxins, Immune-response and Cell Signaling, Instituto Butantan, São Paulo, SP, 05503-900, Brazil.

Malignant transformation involves an orchestrated rearrangement of cell cycle regulation mechanisms that must balance autonomic mitogenic impulses and deleterious oncogenic stress. Human papillomavirus (HPV) infection is highly prevalent in populations around the globe, whereas the incidence of cervical cancer is 0.15%. Read More

Cell Death Dis 2021 Feb 18;12(2):192. Epub 2021 Feb 18.

Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00, Brno, Czech Republic.

Many cancer therapies aim to trigger apoptosis in cancer cells. Nevertheless, the presence of oncogenic alterations in these cells and distorted composition of tumour microenvironment largely limit the clinical efficacy of this type of therapy. Luckily, scientific consensus describes about 10 different cell death subroutines with different regulatory pathways and cancer cells are probably not able to avoid all of cell death types at once. Read More

Exp Hematol 2021 Feb 16. Epub 2021 Feb 16.

Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. Electronic address:

RUNX3, a transcription factor, has been implicated as a tumor suppressor in various cancers, including hematological malignancies; however, recent studies revealed an oncogenic function of RUNX3 in the pathogenesis of myeloid malignancies, such as myelodysplastic syndrome and acute myeloid leukemia. In contrast to the high frequency of mutations in the RUNX1 gene, deletion of and loss-of-function mutations in RUNX3 are rarely detected in patients with hematopoietic malignancies. Although RUNX3 is expressed in normal hematopoietic stem and progenitor cells, its expression decreases with aging in humans. Read More

Int Immunopharmacol 2021 Feb 10;94:107443. Epub 2021 Feb 10.

School of Pharmacy, Anhui Medical University, Hefei, China; The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address:

Background: Programmed cell death receptor 1 (PD-1) is an immunosuppressive molecule expressed on T cells, and its ligand (PD-L1) which expressed on tumor cells play pivotal roles in regulating host immune responses. However, little is known whether PD-1/PD-L1 axis could directly activates intracellular oncogenic signaling pathways in tumor cells, leading to tumor resistance.

Methods: In the present study, the expression of PD-1 and PD-L1 in the tissues of gastric cancer was detected by western blot and immunofluorescence. Read More