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Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review.

Aging (Albany NY) 2021 Jun 11;13. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Changhai Hospital, Naval Military Medical University, Yangpu, Shanghai 200433, China.

Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but also fulfill various physiopathological functions in extraocular tissues. βB2-crystallin, for example, is a multifunctional protein expressed in the human retina, brain, testis, ovary, and multiple tumors. Mutations in the βB2 crystallin gene or denaturation of βB2-crystallin protein are associated with cataracts, ocular pathologies, and psychiatric disorders. Read More

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Design, synthesis, and biological evaluation of novel bifunctional thyrointegrin antagonists for neuroblastoma.

Bioorg Med Chem 2021 Jun 6;42:116250. Epub 2021 Jun 6.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, United States. Electronic address:

Receptor-mediated cancer therapy has received much attention in the last few decades. Neuroblastoma and other cancers of the sympathetic nervous system highly express norepinephrine transporter (NET) and cell plasma membrane integrin αvβ3. Dual targeting of the NET and integrin αvβ3 receptors using a Drug-Drug Conjugate (DDC) might provide effective treatment strategy in the fight against neuroblastoma and other neuroendocrine tumors. Read More

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Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery.

ESMO Open 2021 Jun 9;6(4):100178. Epub 2021 Jun 9.

Department of Drug Development and Innovation (D3i), Institut Curie, Paris and Saint-Cloud, France. Electronic address:

Background: Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters. Read More

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MUC1 regulates AKT signaling pathway by upregulating EGFR expression in ovarian cancer cells.

Pathol Res Pract 2021 Jun 4;224:153509. Epub 2021 Jun 4.

School of Basic Medical Sciences, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China. Electronic address:

MUC1, a type I transmembrane glycoprotein, mediates tumor growth and cellular differentiation in various types of cancers. However, the mechanism of MUCI in ovarian cancer has not been fully clarified. In our study, we have observed that MUC1 can play a crucial role in the development and progression of ovarian cancer and act as a predictive marker. Read More

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HOXB5 promotes the progression of breast cancer through wnt/beta-catenin pathway.

Pathol Res Pract 2020 Jul 13;224:153117. Epub 2020 Jul 13.

National Clinical Research Center for Normal Aging and Geriatric & The Key Lab of Normal Aging and Geriatric, Institute of Geriatric, PLA General Hospital, Beijing, China. Electronic address:

Objective: The present study was designed to explore the function of HOXB5 in breast cancer and related signaling pathway.

Methods: Breast cancer tissues and non-cancerous tissues were collected from 82 cases who were pathologically diagnosed with breast cancer. The mRNA level of HOXB5 was detected via quantitative real-time polymerase chain reaction (qRT-PCR). Read More

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High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.

Transl Oncol 2021 Jun 9;14(8):101146. Epub 2021 Jun 9.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai 200011, China; Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Read More

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Anti-tumor effects of rigosertib in high-risk neuroblastoma.

Transl Oncol 2021 Jun 9;14(8):101149. Epub 2021 Jun 9.

Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden. Electronic address:

High-risk neuroblastoma has a poor prognosis despite intense treatment, demonstrating the need for new therapeutic strategies. Here we evaluated the effects of rigosertib (ON-01910.Na) in preclinical models of high-risk neuroblastoma. Read More

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HIF-1α-activated TM4SF1-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by enhancing TM4SF1 expression.

Biochem Biophys Res Commun 2021 Jun 9;566:80-86. Epub 2021 Jun 9.

The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China. Electronic address:

Long non-coding RNAs (lncRNAs) are essential drivers or suppressors in human hepatocellular carcinoma (HCC) by participating in controlling transcription, translation, mRNA stability, and protein degradation protein-protein interaction. TM4SF1-AS1 is recently identified as a tumor-promoting factor in lung cancer. Nevertheless, its function in HCC and related molecular mechanisms remain unknown. Read More

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β3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis.

Biochem Biophys Res Commun 2021 Jun 9;566:75-79. Epub 2021 Jun 9.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China; School of Life Sciences, Shanghai University, Shanghai, China; Versiti Blood Research Institute, Milwaukee, WI, USA; Department of Biochemistry, Medical College of Milwaukee, Wisconsin, USA. Electronic address:

Anti-angiogenesis serves as an effective tumor therapy approach. In a previous study, we found that β3-endonexin expressed in vascular endothelial cells was involved in promoting proliferation and angiogenesis partially by facilitating VEGF expression. However, it still remains unclear if β3-endonexin in vascular endothelial cells also employs other mechanisms in regulating angiogenesis. Read More

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Loss of ATRX confers DNA repair defects and PARP inhibitor sensitivity.

Transl Oncol 2021 Jun 9;14(9):101147. Epub 2021 Jun 9.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06511, USA. Electronic address:

Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) is mutated frequently in gliomas and represents a potential target for cancer therapies. ATRX is known to function as a histone chaperone that helps incorporate histone variant, H3.3, into the genome. Read More

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Transfer of small interfering RNA by electropermeabilization in tumor spheroids.

Bioelectrochemistry 2021 May 25;141:107848. Epub 2021 May 25.

Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France. Electronic address:

The ability to modulate deregulated genes by RNAi provides treatment perspectives in certain diseases including cancers. Electrotransfer of oligonucleotides was studied in vitro, showing a direct transfer of negatively charged siRNA across the plasma membrane into the cytoplasm. In vivo, the feasibility of siRNA electrotransfer was demonstrated in different studies and tissues. Read More

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Glycoproteogenomics: Setting the Course for Next Generation Cancer Neoantigens Discovery for Cancer Vaccines.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto 4200-072, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto 4050-313, Portugal; Porto Comprehensive Cancer Center (P.ccc), Porto 4200-072, Portugal.

Molecular-assisted precision oncology gained tremendous ground with high throughput next-generation sequencing (NGS), supported by robust bioinformatics. The quest for genomics-based cancer medicine set the foundations for improved patient stratification, while unveiling a wide array of neoantigens for immunotherapy. Upfront pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target effects. Read More

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Reply to "Commentary on: Risk factors for postoperative morbidity after thyroid surgery in a PROSPECTIVE cohort of 1500 patients (Int. J. Surg. 2021, Epub ahead of print)".

Int J Surg 2021 Jun 9:105994. Epub 2021 Jun 9.

Centre for Translational Microbiome Research Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Global Health Institute, University of Antwerp, Wilrijk, Belgium.

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Androgen receptor (AR) heterogeneity in prostate cancer and therapy resistance.

Cancer Lett 2021 Jun 9. Epub 2021 Jun 9.

Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA; Experimental Therapeutics (ET) Graduate Program, University at Buffalo & Roswell Park Comprehensive Cancer Center, NY, 14263, USA. Electronic address:

Androgen receptor (AR), a ligand-dependent nuclear transcription factor and a member of steroid hormone receptor family, plays an important role in prostate organogenesis by regulating epithelial differentiation and restricting cell proliferation. Although rarely mutated or amplified in treatment-naïve prostate cancer (PCa), AR signaling drives tumor growth and as a result, therapies that aim to inhibit AR signaling, called ARSIs (AR signaling inhibitors), have been in clinical use for >70 years. Unfortunately, the clinical efficacy of ARSIs is short-lived and the majority of treated patients develop castration-resistant PCa (CRPC). Read More

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Unfolding the Apoptotic Mechanism of Antioxidant Enriched-Leaves of Tabebuia pallida (Lindl.) Miers in EAC Cells and Mouse Model.

J Ethnopharmacol 2021 Jun 9:114297. Epub 2021 Jun 9.

Department of Pharmacy, University of Rajshahi, Rajshahi-6205, Bangladesh. Electronic address:

Ethnopharmacological Relevance: Tabebuia pallida (Lindl.) Miers (T. pallida) is a well-known native Caribbean medicinal plant. Read More

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Revealing the Mechanism of "Huai Hua San" in the Treatment of Ulcerative Colitis based on Network Pharmacology and Experimental Study.

J Ethnopharmacol 2021 Jun 9:114321. Epub 2021 Jun 9.

Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, 430065, China; Collaborative Innovation Center of Traditional Chinese Medicine of New Products for Geriatrics Hubei Province, Wuhan, 430065, China. Electronic address:

Ethnopharmacological Relevance: "Huai Hua San" (HHS) is one of the first hundred ancient classic prescriptions drugs, which is commonly used to treat hemorrhoids, colitis, and other symptoms of wind heat in stool. However, the potential molecular mechanism of action of this substance remains unclear.

Aims Of The Study: In this study, we explored the active compounds of HHS for the treatment of ulcerative colitis (UC), predicted the potential targets of the drug, and studied its mechanism of action through network pharmacology via in vitro and in vivo experiments. Read More

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Alpha lipoic acid priming enhances the hepatoprotective effect of adipose derived stem cells in CCl4 induced hepatic injury in-vitro.

Eur J Pharmacol 2021 Jun 9:174201. Epub 2021 Jun 9.

National Centre of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Lahore, Pakistan; Jinnah Burn & Reconstructive Surgery Centre, Lahore, Pakistan. Electronic address:

Mesenchymal stem cells are known to support hepatic defense against liver fibrosis. However, the fibrosis induced oxidative microenvironment affects the proliferative, regenerative, and angiogenic properties of mesenchymal stem cells. Alpha lipoic acid (ALA) is a strong anti-oxidant which has been shown to ameliorate the adverse effects of fibrosis that otherwise can lead to severe liver problems like cirrhosis and liver failure. Read More

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Characterization of the immune cell infiltration landscape in bladder cancer to aid immunotherapy.

Arch Biochem Biophys 2021 Jun 9:108950. Epub 2021 Jun 9.

Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China. Electronic address:

The tumor microenvironment (TME) is composed mainly of tumor cells, tumorinfiltrating immune cells, and matrix components. Recent clinical studies have indicated that tumor immune cell infiltration (ICI) is related to the sensitivity of immunotherapy and the prognosis of patients with bladder cancer (BC). Nevertheless, up to now, the landscape of immune infiltration in BC has not been clearly defined. Read More

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Oncogene-regulated release of extracellular vesicles.

Dev Cell 2021 Jun 8. Epub 2021 Jun 8.

Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Oncogenes can alter metabolism by changing the balance between anabolic and catabolic processes. However, how oncogenes regulate tumor cell biomass remains poorly understood. Using isogenic MCF10A cells transformed with nine different oncogenes, we show that specific oncogenes reduce the biomass of cancer cells by promoting extracellular vesicle (EV) release. Read More

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Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study.

Lancet Oncol 2021 Jun 9. Epub 2021 Jun 9.

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Oncogenic alterations in RET have been identified in multiple tumour types, including 1-2% of non-small-cell lung cancers (NSCLCs). We aimed to assess the safety, tolerability, and antitumour activity of pralsetinib, a highly potent, oral, selective RET inhibitor, in patients with RET fusion-positive NSCLC.

Methods: ARROW is a multi-cohort, open-label, phase 1/2 study done at 71 sites (community and academic cancer centres) in 13 countries (Belgium, China, France, Germany, Hong Kong, Italy, Netherlands, Singapore, South Korea, Spain, Taiwan, the UK, and the USA). Read More

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Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects.

Cell Metab 2021 Jun 8. Epub 2021 Jun 8.

Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, 57 Avenue Hippocrate B1.5704, 1200 Brussels, Belgium. Electronic address:

Tumor acidosis promotes disease progression through a stimulation of fatty acid (FA) metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells, we examined whether excess uptake of specific FAs could lead to antitumor effects. We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively induced ferroptosis in cancer cells under ambient acidosis. Read More

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In Situ Tumor Vaccination with Nanoparticle Co-Delivering CpG and STAT3 siRNA to Effectively Induce Whole-Body Antitumor Immune Response.

Adv Mater 2021 Jun 12:e2100628. Epub 2021 Jun 12.

PDX Pharmaceuticals, Inc., Portland, OR, 97239, USA.

The success of immunotherapy with immune checkpoint inhibitors (ICIs) in a subset of individuals has been very exciting. However, in many cancers, responses to current ICIs are modest and are seen only in a small subsets of patients. Herein, a widely applicable approach that increases the benefit of ICIs is reported. Read More

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Upregulation of centromere protein K is crucial for lung adenocarcinoma cell viability and invasion.

Adv Clin Exp Med 2021 Jun 11. Epub 2021 Jun 11.

Medical Laboratory, Second Affiliated Hospital of Mudanjiang Medical University, China.

Background: Identification of functional genes or biomarkers may be helpful for developing new treatment strategies in lung adenocarcinoma (LUAD). The centromere protein K (CENPK) gene has been discovered to be overexpressed and could influence tumor progression in several tumor types. However, its role in LUAD has never been revealed. Read More

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FGF21 promotes wound healing of rat brain microvascular endothelial cells through facilitating TNF-α-mediated VEGFA and ERK1/2 signaling pathway.

Adv Clin Exp Med 2021 Jun 11. Epub 2021 Jun 11.

No. 1 Department of Orthopedics, The Third People's Hospital, Cixi, China.

Background: Wound healing is an essential physiological process in recovery after microsurgery.

Objectives: To further understand the functions of fibroblast growth factor 21 (FGF21), the roles of this factor were examined and its correlations with inflammation, vascular endothelial growth factor A (VEGFA) and ERK1/2 signaling pathway activation were analyzed.

Material And Methods: Rat brain microvascular endothelial cells (RBMECs) were treated with interleukin (IL)-1β and used for the experiments. Read More

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MiR-124 protects against cognitive dysfunction induced by sevoflurane anesthesia in vivo and in vitro through targeting calpain small subunit 1 via NF-κB signaling pathway.

Adv Clin Exp Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Postoperative cognitive dysfunction (POCD) is an impairment of cognition that affects post-surgery patients. Sevoflurane anesthesia is linked to cognitive dysfunction correlated to the expression of miRNA levels.

Objectives: In the current study, we investigated if miR-124 can offer protection against cognitive deficits induced by sevoflurane in a spatial learning paradigm, and examined the molecular mechanisms through cell cultures. Read More

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Co-existence of multiple myeloma and perivascular endothelial cell tumor.

Int J Lab Hematol 2021 Jun 12. Epub 2021 Jun 12.

Laboratory Medicine Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.

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Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β-catenin/ZEB1 axis.

Cancer Sci 2021 Jun 12. Epub 2021 Jun 12.

Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Seoul, Korea.

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular-based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Read More

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The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells.

FASEB J 2021 Jul;35(7):e21692

Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

For metastasis formation, individual cells from a primary tumor must migrate toward other tissues. The aim of this study was to determine if mesenchymal stromal cells (MSCs) from human bone marrow are able to emit signals that induce this migratory activity in cancer cells. We separated the supernatant of MSCs derived from human bone marrow by size-exclusion and ion-exchange chromatography and have subsequently studied the migratory behavior of the prostate cancer cell line PC3 and the breast cancer cell line MDA-MB-231 toward the respective fractions in a transwell migration assay. Read More

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Development of Mitochondria-Targeted Imaging Nanoplatforms by Incorporation of Fluorescent Carbon Quantum Dots.

Authors:
Ye Zhang Hong Bi

Methods Mol Biol 2021 ;2275:265-277

School of Chemistry and Chemical Engineering, Anhui University, Hefei, China.

Multifunctional nanoplatforms are promising scaffolds for biomedical applications such as bioimaging, chemical/biological sensors, drug delivery, and cancer diagnosis and/or treatments. Mitochondria play crucial roles in metabolism of eukaryotic cells; therefore, mitochondria-targeting molecule such as triphenylphosphonium (TPP) is attached onto the magnetic mesoporous silica nanoparticle ([email protected]). In order to track the nanoparticles, fluorescent carbon quantum dots (CDs) were conjugated to the [email protected] Read More

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January 2021

Liposomal Delivery of Cyclocreatine Impairs Cancer Cell Bioenergetics Mediating Apoptosis.

Methods Mol Biol 2021 ;2275:173-186

Department of Pharmaceutical Sciences, College of Pharmacy-Glendale Campus, Midwestern University, Glendale, AZ, USA.

Creatine kinase (CK) enzyme overexpression has been suggested to play a role in the process of tumorigenesis and metastasis. Cyclocreatine (CCR) is a substrate analog of creatine kinase (CK), where its phosphorylated form is a poor phosphate donor in comparison with native bioenergetic molecule, creatine phosphate (Cr-P). The compound CCR has been shown to markedly inhibit the growth of a broad spectrum of cancers, both in vitro and in vivo. Read More

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January 2021