31,472 results match your criteria p53 mutations

Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis.

Nat Commun 2021 Apr 16;12(1):2280. Epub 2021 Apr 16.

Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

The tumor suppressor p53 is mutated in approximately half of all human cancers. p53 can induce apoptosis through mitochondrial membrane permeabilization by interacting with and antagonizing the anti-apoptotic proteins BCL-xL and BCL-2. However, the mechanisms by which p53 induces mitochondrial apoptosis remain elusive. Read More

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High prevalence of developmental venous anomaly in adult patients with midline thalamic diffuse gliomas.

J Clin Neurosci 2021 May 11;87:59-65. Epub 2021 Mar 11.

Department of Neurosurgery, West China Hospital, Chengdu, Sichuan Province, PR China. Electronic address:

Objective: This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation.

Patients And Methods: Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Read More

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Mutant p53 in cell-cell interactions.

Genes Dev 2021 Apr;35(7-8):433-448

The Francis Crick Institute, London NW1 1AT, United Kingdom.

p53 is an important tumor suppressor, and the complexities of p53 function in regulating cancer cell behaviour are well established. Many cancers lose or express mutant forms of p53, with evidence that the type of alteration affecting p53 may differentially impact cancer development and progression. It is also clear that in addition to cell-autonomous functions, p53 status also affects the way cancer cells interact with each other. Read More

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Activated p53 in the anti-apoptotic milieu of tuberous sclerosis gene mutation induced diseases leads to cell death if thioredoxin reductase is inhibited.

Apoptosis 2021 Apr 16. Epub 2021 Apr 16.

Department of Pharmaceutical Biotechnology, University of Pecs, Pecs, Hungary.

Tuberous sclerosis, angiomyolipoma and lymphangioleiomyomatosis are a group of diseases characterized by mutation in tuberous sclerosis genes (TSC 1-2). TSC mutation leads to continuous activation of the mTOR pathway that requires adaptation to increased ATP requirement. With limited treatment options, there is an increasing demand to identify novel therapeutic targets and to understand the correlations between mTOR pathway activation and the lack of cell death in the presence of TSC mutation. Read More

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Polymorphous low-grade neuroepithelial tumor of the young: A detailed patho-molecular analysis and discussion of a case.

Clin Neuropathol 2021 Apr 16. Epub 2021 Apr 16.

Aim: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a rare entity with a diffuse, infiltrative pattern, awaiting to be included in the WHO CNS tumor classification; it occurs in pediatric and young patients with seizures and harbors mutually exclusive BRAFV600E or FGFR mutations. Nonetheless, the presence of these mutations may not be obligatory for diagnosis. The conventional histology of these tumors resembles that of oligodendrogliomas. Read More

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The role of the aqueous extract Polypodium leucotomos in photoprotection.

Photochem Photobiol Sci 2020 Jun 27;19(6):831-843. Epub 2020 Oct 27.

Medicine and Medical Specialties Department, Alcala University, Madrid, Spain.

Solar radiation in the ultraviolet (UV), visible (VIS), and infrared (IR) ranges produces different biological effects in humans. Most of these, particularly those derived from ultraviolet radiation (UVR) are harmful to the skin, and include cutaneous aging and increased risk of cutaneous diseases, particularly skin cancer. Pharmacological photoprotection is mostly topical, but it can also be systemic. Read More

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The Prediction of Recurrence in Low-Risk Endometrial Cancer: Is It Time for a Paradigm Shift in Adjuvant Therapy?

Reprod Sci 2021 Apr 15. Epub 2021 Apr 15.

The Department of Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt.

Five to 10% of patients with stage IA, grade 1 or 2, endometrioid adenocarcinoma subsequently develop locoregional or distant recurrence. These patients have significantly reduced 5-year survival rates and salvage therapy success rates as low as 40%. The aim of this review is to highlight knowledge gaps that could further refine the risk categories of endometrial carcinoma (EC) and guide future randomized trials of adjuvant therapy for low-risk EC. Read More

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Human papillomavirus, gene mutation and estrogen and progesterone receptors in breast cancer: a cross-sectional study.

Pan Afr Med J 2021 15;38:43. Epub 2021 Jan 15.

Department of Histology and Cytology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Introduction: recent studies show a good relationship between breast cancer (BC) and human papillomaviruses (HPV) wich is responsible for about 18% of BC cases. This study aimed to assess the relationship between different genotypes of HPV and the expression of P53 and retinoblastoma (RB) genes and estrogen and progesterone receptors in BC among Sudanese women.

Methods: one hundred and fifty tissue blocks were obtained from females diagnosed with BC. Read More

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January 2021

Bevacizumab Plays a double-edged role in Neoadjuvant Therapy for Non-metastatic Breast Cancer: A Systemic Review and Meta-Analysis.

J Cancer 2021 5;12(9):2643-2653. Epub 2021 Mar 5.

Oncology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Back Road of Art Gallery, Dongcheng District, Beijing, 100010, China.

The anti-angiogenic drug Bevacizumab (Bev) is engaged in neoadjuvant therapy for non-metastatic breast cancer (NMBC). However, whether neoadjuvant Bev providing a greater benefit to patients is debatable. Our study aimed to review Bev's role in Neoadjuvant therapy (NAT) in NMBC and identify predictive markers associated with its efficacy by systemic review and meta-analysis. Read More

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Diagnostic roles of proliferative markers in pathological Grade of T1 Urothelial Bladder Cancer.

J Cancer 2021 5;12(9):2498-2506. Epub 2021 Mar 5.

Department of Pathology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

The stage T1 urothelial bladder cancer (T1 UBC) tumor grade classification is important for prognosis and clinical management. However, the reproducibility of this two-grade classification system is limited in regards to pathological diagnosis, and there is lack of ideal, objective and easily detected markers for pathological diagnosis. In our study, bladder urothelial lesions from a total of 124 patients diagnosed pathologically after transurethral resection of the bladder tumor (TURBT) were collected, including non-cancerous lesions from 33 patients and lesions from 91 T1 UBC patients. Read More

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Genomic alterations impact cell cycle-related genes during prostate cancer progression.

Endocr Relat Cancer 2021 Apr 1. Epub 2021 Apr 1.

H Heemers, Cancer Biology, Cleveland Clinic, Cleveland, 44195, United States.

The recent genomic characterization of patient specimens has started to reveal the landscape of somatic alterations in clinical prostate cancer (CaP) and its association with disease progression and treatment resistance. The extent to which such alterations impact hallmarks of cancer is still unclear. Here, we interrogate genomic data from thousands of clinical CaP specimens that reflect progression from treatment-naïve, to castration-recurrent, and in some cases, neuroendocrine CaP for alterations in cell cycle-associated and -regulated genes, which are central to cancer initiation and progression. Read More

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Insight into del17p low-frequency subclones in chronic lymphocytic leukaemia (CLL): data from the Australasian Leukaemia and Lymphoma Group (ALLG)/CLL Australian Research Consortium (CLLARC) CLL5 trial.

Br J Haematol 2021 Apr 13. Epub 2021 Apr 13.

Department of Molecular Medicine and Genetics, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA.

The clinical significance of low-frequency deletions of 17p13 [tumour protein p53 (TP53)] in patients with chronic lymphocytic leukaemia (CLL) is currently unclear. Low-frequency del17p clones (<25%) were identified in 15/95 patients in the Australasian Leukaemia and Lymphoma Group (ALLG)/CLL Australian Research Consortium (CLLARC) CLL5 trial. Patients with low del17p, without tumour protein p53 (TP53) mutation, had significantly longer progression-free survival and overall survival durations than patients with high del17p clones. Read More

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A metabolism-related gene signature for predicting the prognosis and therapeutic responses in patients with hepatocellular carcinoma.

Ann Transl Med 2021 Mar;9(6):500

Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China.

Background: Hepatocellular carcinoma (HCC) often has an insidious onset and rapid progression. Often, when the disease is first diagnosed, the opportune time for surgical intervention has already lapsed. In addition, the effects of systemic treatment is relatively unsatisfactory. Read More

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Bcl-xL Dynamics under the Lens of Protein Structure Networks.

J Phys Chem B 2021 Apr 13. Epub 2021 Apr 13.

Computational Biology Laboratory, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Understanding the finely orchestrated interactions leading to or preventing programmed cell death (apoptosis) is of utmost importance in cancer research because the failure of these systems could eventually lead to the onset of the disease. In this regard, the maintenance of a delicate balance between the promoters and inhibitors of mitochondrial apoptosis is crucial, as demonstrated by the interplay among the Bcl-2 family members. In particular, B-cell lymphoma extra-large (Bcl-x) is a target of interest due to the forefront role of its dysfunctions in cancer development. Read More

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Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis.

Oncol Lett 2021 May 16;21(5):381. Epub 2021 Mar 16.

Department of Pathology, Erasmus MC, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands.

Vulvar squamous cell carcinoma (VSCC) comprises two distinct etiopathological subtypes: i) Human papilloma virus (HPV)-related VSCC, which arises via the precursor high grade squamous intraepithelial lesion (HSIL); and ii) HPV-independent VSCC, which arises via precursor, differentiated vulvar intraepithelial neoplasia (dVIN), driven by mutations. However, the mechanism of carcinogenesis of VSCC is poorly understood. The current study aimed to gain insight into VSCC carcinogenesis by identifying differentially expressed genes (DEGs) for each VSCC subtype. Read More

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Oncogenic KRAS recruits an expansive transcriptional network through mutant p53 to drive pancreatic cancer metastasis.

Cancer Discov 2021 Apr 10. Epub 2021 Apr 10.

Genetics, The University of Texas MD Anderson Cancer Center.

Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic KRAS mutations prevail in 95% of PDAC tumors and co-occur with genetic alterations in the TP53 tumor suppressor in nearly 70% of patients. Most TP53 alterations are missense mutations that exhibit gain-of-function phenotypes that include increased invasiveness and metastasis yet the extent of direct cooperation between KRAS effectors and mutant p53 remains largely undefined. Read More

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Undifferentiated colonic neoplasm with SMARCA4 germline gene mutation and loss of SMARCA4 protein expression: a case report and literature review.

Diagn Pathol 2021 Apr 9;16(1):30. Epub 2021 Apr 9.

Department of Pathology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, China.

Background: Nonsense mutation or inactivation of SMARCA4 (BRG1) is associated with a monomorphic undifferentiated histological appearance in tumors at different sites. The association between SMARCA4 alteration and undifferentiated colonic carcinoma needs to be further elucidated.

Methods: A 61-year-old male patient presented to the hospital with intermittent epigastric pain in the right upper abdomen and abdominal distension. Read More

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Development of p53 knockout U87MG cell line for unbiased drug delivery testing system using CRISPR-Cas9 and transcriptomic analysis.

J Biotechnol 2021 Apr 6;332:72-82. Epub 2021 Apr 6.

RIKEN Center for Integrative Medical Sciences, Japan. Electronic address:

Antibody-drug conjugates offers many advantages as a drug delivery platform that allows for highly specific targeting of cell types and genes. Ideally, testing the efficacy of these systems requires two cell types to be different only in the gene targeted by the drug, with the rest of the cellular machinery unchanged, in order to minimize other potential differences from obscuring the effects of the drug. In this study, we created multiple variants of U87MG cells with targeted mutation in the TP53 gene using the CRISPR-Cas9 system, and determined that their major transcriptional differences stem from the loss of p53 function. Read More

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Comprehensive mutagenesis identifies the peptide repertoire of a p53 T-cell receptor mimic antibody that displays no toxicity in mice transgenic for human HLA-A*0201.

PLoS One 2021 9;16(4):e0249967. Epub 2021 Apr 9.

Nuffield Division of Clinical Laboratory Science, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.

T-cell receptor mimic (TCRm) antibodies have expanded the repertoire of antigens targetable by monoclonal antibodies, to include peptides derived from intracellular proteins that are presented by major histocompatibility complex class I (MHC-I) molecules on the cell surface. We have previously used this approach to target p53, which represents a valuable target for cancer immunotherapy because of the high frequency of its deregulation by mutation or other mechanisms. The T1-116C TCRm antibody targets the wild type p5365-73 peptide (RMPEAAPPV) presented by HLA-A*0201 (HLA-A2) and exhibited in vivo efficacy against triple receptor negative breast cancer xenografts. Read More

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High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs.

PLoS One 2021 9;16(4):e0248984. Epub 2021 Apr 9.

Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.

The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Read More

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Lead Borate Nanoparticles Induce Apoptotic Gene Activity in P53 Mutant Cancer Cells.

Biol Trace Elem Res 2021 Apr 8. Epub 2021 Apr 8.

Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 26 Ağustos Campus, Kayisdagi cad., Kayisdagi, TR-34755, Istanbul, Turkey.

Cancer is a complex and multistage disease that causes suffering worldwide. Several mutations in tumor suppressor proteins are mostly responsible for tumorigenic development. Thus, determination of the mutations and developing a mutation targeted therapy are crucial in order to cure cancer. Read More

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Genomic characterization of small cell carcinomas of the uterine cervix.

Mol Oncol 2021 Apr 8. Epub 2021 Apr 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)-positive head and neck squamous cell carcinomas, HPV-positive cervical carcinomas and SCLCs using publicly available data. Using a combination of whole-exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18-positive (n=8) or HPV16-positive (n=1), harbored a low mutation burden, few copy number alterations and other than TP53 in two cases no recurrently mutated genes. Read More

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What do we need to know and understand about p53 to improve its clinical value?

J Pathol 2021 Apr 7. Epub 2021 Apr 7.

Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, F-75010, Paris, France.

Few proteins are more studied than the p53 tumour suppressor, but what have we learned from these studies and what do we really know about p53 that can benefit clinical practice? The DNA sequence encoding p53 is frequently mutated in cancers but the functional outcomes of single mutations, in respect to loss or gain of different activities, especially in relation to immune evasion, is not clear. This illustrates p53's complexity which even after 40 years keeps providing surprises, but also explains why it has not yet lived up to its potential to benefit cancer treatment. We have reassessed a few key experiments that shaped the p53 field and we take a closer look at the interpretations of these experiments; what they have taught us, the resulting dogmas, and their potential clinical importance. Read More

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AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth.

Cell Death Dis 2021 Apr 6;12(4):365. Epub 2021 Apr 6.

Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Activation of adenosine monophosphate-activated protein kinase (AMPK) is able to produce significant anti-non-small cell lung cancer (NSCLC) cell activity. ASP4132 is an orally active and highly effective AMPK activator. The current study tested its activity against NSCLC cells. Read More

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Uncovering the dosage-dependent roles of Arid1a in gastric tumorigenesis for combinatorial drug therapy.

J Exp Med 2021 06;218(6)

Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Gastric cancer (GC) is one of the most common deadly cancers in the world. Although patient genomic data have identified AT-rich interaction domain 1A (ARID1A), a key chromatin remodeling complex subunit, as the second most frequently mutated gene after TP53, its in vivo role and relationship to TP53 in gastric tumorigenesis remains unclear. Establishing a novel mouse model that reflects the ARID1A heterozygous mutations found in the majority of human GC cases, we demonstrated that Arid1a heterozygosity facilitates tumor progression through a global loss of enhancers and subsequent suppression of the p53 and apoptosis pathways. Read More

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Integrative bioinformatics analysis of KPNA2 in six major human cancers.

Chaobo Xu Ming Liu

Open Med (Wars) 2021 30;16(1):498-511. Epub 2021 Mar 30.

Department of Gastrointestinal Surgery, Lishui People's Hospital, No. 15 Dazhong Road, Liandu District, Lishui 323000, Zhejiang, China.

Background: Malignant tumors were considered as the leading causes of cancer-related mortality globally. More and more studies found that dysregulated genes played an important role in carcinogenesis. The aim of this study was to explore the significance of KPNA2 in human six major cancers including non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer, breast cancer, hepatocellular carcinoma, and bladder cancer based on bioinformatics analysis. Read More

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Machine learning-based investigation of the cancer protein secretory pathway.

PLoS Comput Biol 2021 Apr 5;17(4):e1008898. Epub 2021 Apr 5.

Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.

Deregulation of the protein secretory pathway (PSP) is linked to many hallmarks of cancer, such as promoting tissue invasion and modulating cell-cell signaling. The collection of secreted proteins processed by the PSP, known as the secretome, is often studied due to its potential as a reservoir of tumor biomarkers. However, there has been less focus on the protein components of the secretory machinery itself. Read More

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Clinical Features of Breast Cancer in South Korean Patients with Germline Gene Mutations.

J Breast Cancer 2021 Mar 12. Epub 2021 Mar 12.

Division of Breast Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline mutations. Read More

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Expression of TMEM16A in Colorectal Cancer and Its Correlation With Clinical and Pathological Parameters.

Front Oncol 2021 19;11:652262. Epub 2021 Mar 19.

Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Second Hospital of Jilin University, Changchun, China.

TMEM16A is a recently identified calcium-activated chloride channel (CaCC) and its overexpression contributes to tumorigenesis and progression in several human malignancies. However, little is known about expression of TMEM16A and its clinical significance in colorectal cancer (CRC). TMEM16A mRNA expression was determined by quantitative real time-PCR (qRT-PCR) in 67 CRC tissues and 24 para-carcinoma tissues. Read More

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