90,346 results match your criteria development targeted

TAK1 is a novel target in Hepatocellular Carcinoma and contributes to sorafenib resistance.

Cell Mol Gastroenterol Hepatol 2021 May 4. Epub 2021 May 4.

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China; Zhejiang University Cancer Center, 310058, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China. Electronic address:

Background & Aims: Identifying novel and actional targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a TGF-β-activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. However, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood. Read More

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Baby-led weaning in Italy and potential implications for infant development.

Appetite 2021 May 4:105286. Epub 2021 May 4.

Deparment of Psychology, College of Health and Life Sciences, Aston University, Aston Triangle, B4 7ET Birmingham, UK. Electronic address:

Baby-led weaning is an approach to complementary feeding that emphasizes an infant's ability to self-feed rather than being spoon fed, and to eat minimally-processed foods rather than puréed foods. This study aimed to investigate the variability in infant feeding practices and the possible association with developmental milestones in an Italian population. A sample of 1245 mothers of 6-12 month-old infants completed an online survey about complementary feeding and their infant's attainment of developmental milestones. Read More

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Adamantyl Isothiocyanates as Mutant p53 Rescuing Agents and Their Structure-Activity Relationships.

J Med Chem 2021 May 7. Epub 2021 May 7.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20007, United States.

Mutant p53 rescue by small molecules is a promising therapeutic strategy. In this structure-activity relationship study, we examined a series of adamantyl isothiocyanates (Ad-ITCs) to discover novel agents as therapeutics by targeting mutant p53. We demonstrated that the alkyl chain connecting adamantane and ITC is a crucial determinant for Ad-ITC inhibitory potency. Read More

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RGD-Peptide Functionalization Affects the Diffusion of a Responsive Trimeric MRI Contrast Agent through Interactions with Integrins.

J Med Chem 2021 May 7. Epub 2021 May 7.

Max Planck Institute for Biological Cybernetics, Department for Physiology of Cognitive Processes, Max-Planck-Ring 11, 72072 Tübingen, Germany.

The relevance of MRI as a diagnostic methodology has been expanding significantly with the development of molecular imaging. Partially, the credit for this advancement is due to the increasing potential and performance of targeted MRI contrast agents, which are able to specifically bind distinct receptors or biomarkers. Consequently, these allow for the identification of tissues undergoing a disease, resulting in the over- or underexpression of the particular molecular targets. Read More

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Current management of melanoma patients with nodal metastases.

Clin Exp Metastasis 2021 May 7. Epub 2021 May 7.

Department of Surgery, Morsani School of Medicine, University of South Florida, Tampa, FL, USA.

The management of melanoma patients with nodal metastases has undergone dramatic changes over the last decade. In the past, the standard of care for patients with a positive sentinel lymph node biopsy (SLNB) was a completion lymph node dissection (CLND), while patients with palpable macroscopic nodal disease underwent a therapeutic lymphadenectomy in cases with no evidence of systemic spread. However, studies have shown that SLN metastases present as a spectrum of disease, with certain SLN-based factors being prognostic of and correlated with outcomes. Read More

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Drug Repurposing: Claiming the Full Benefit from Drug Development.

Curr Cardiol Rep 2021 May 7;23(6):62. Epub 2021 May 7.

DeVos Cardiovascular Research Program, Van Andel Institute/Spectrum Health, Grand Rapids, MI, USA.

Purpose Of Review: Drug development has evolved over the years from being one-at-a-time to be massive screens in an industrial manner. Bringing a new therapeutic agent from concept to bedside can take a decade and cost billions of dollars-with most concepts failing along the way. Of the few compounds that make it to clinical testing, less than one out of eight make it to approval. Read More

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Integrated microenvironment-associated genomic profiles identify LRRC15 mediating recurrent glioblastoma-associated macrophages infiltration.

J Cell Mol Med 2021 May 7. Epub 2021 May 7.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Glioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. Read More

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Multilevel analysis of geographic variation among correlates of child undernutrition in India.

Matern Child Nutr 2021 May 7:e13197. Epub 2021 May 7.

Harvard Center for Population and Development Studies, Cambridge, Massachusetts, USA.

Prior research has identified a number of risk factors ranging from inadequate household sanitation to maternal characteristics as important determinants of child malnutrition and health in India. What is less known is the extent to which these individual-level risk factors are geographically distributed. Assessing the geographic distribution, especially at multiple levels, matters as it can inform where, and at what level, interventions should be targeted. Read More

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Observation policy for sentinel node metastasis of melanoma: Comparative study with completion lymph node dissection in Japanese patients.

J Dermatol 2021 May 7. Epub 2021 May 7.

Division of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.

Based on the results of international multicenter randomized trials, completion lymph node dissection for patients with sentinel lymph node-positive melanoma is no longer routinely recommended. However, clinicians should take into consideration racial and medical resource differences when applying this evidence to clinical practice in Japan. To evaluate the clinical validity of the observation policy of omitting completion lymph node dissection, we retrospectively surveyed patients with sentinel lymph node-positive melanoma between 2002 and 2020 at Niigata Cancer Center Hospital. Read More

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Scabies Itch: An Update on Neuroimmune Interactions and Novel targets.

J Eur Acad Dermatol Venereol 2021 May 6. Epub 2021 May 6.

Dr Philip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, Miller School of Medicine, University of Miami, Miami.

Frequently described as "the worst itch" one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. Read More

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Extracellular signal-regulated kinase 5 regulates the malignant phenotype of cholangiocarcinoma cells.

Hepatology 2021 May 6. Epub 2021 May 6.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Italy.

Background & Aims: Cholangiocarcinoma (CCA) is characterized by high resistance to chemotherapy and poor prognosis. Several oncogenic pathways converge on activation of extracellular signal-regulated kinase 5 (ERK5), whose role in CCA has not been explored. The aim of this study was to investigate the role of ERK5 in the biology of CCA. Read More

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Impact of Ribosome Activity on SARS-CoV-2 LNP - Based mRNA Vaccines.

Front Mol Biosci 2021 20;8:654866. Epub 2021 Apr 20.

1st ENT Department, Hippocration Hospital, National and Kapodistrian University, Athens, Greece.

Coronavirus-related Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) initially was detected in Wuhan, Hubei, China. Since early 2021, World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19) a pandemic due to rapidly transformed to a globally massive catastrophic viral infection. In order to confront this emergency situation, many pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. Read More

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From Conception to Development: Investigating PROTACs Features for Improved Cell Permeability and Successful Protein Degradation.

Front Chem 2021 20;9:672267. Epub 2021 Apr 20.

School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.

Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional degraders that specifically eliminate targeted proteins by hijacking the ubiquitin-proteasome system (UPS). This modality has emerged as an orthogonal approach to the use of small-molecule inhibitors for knocking down classic targets and disease-related proteins classified, until now, as "undruggable." In early 2019, the first targeted protein degraders reached the clinic, drawing attention to PROTACs as one of the most appealing technology in the drug discovery landscape. Read More

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Oncogenic driver mutations in non-small cell lung cancer: Past, present and future.

World J Clin Oncol 2021 Apr;12(4):217-237

Department of Oncology, University Hospital Geneva, Geneva 1205, Switzerland.

Lung cancer, of which non-small lung cancer is the most common subtype, represents the leading cause of cancer related-death worldwide. It is now recognized that a significant proportion of these patients present alterations in certain genes that drive oncogenesis. In recent years, more of these so-called oncogenic drivers have been identified, and a better understanding of their biology has allowed the development new targeted agents. Read More

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Development of a single-chain fragment variable fused-mutant HALT-1 recombinant immunotoxin against G12V mutated olorectal cancer cells.

PeerJ 2021 15;9:e11063. Epub 2021 Apr 15.

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia.

Background: oncogenes harboring codon G12 and G13 substitutions are considered gatekeeper mutations which drive oncogenesis in many cancers. To date, there are still no target-specific vaccines or drugs available against this genotype, thus reinforcing the need towards the development of targeted therapies such as immunotoxins.

Methods: This study aims to develop a recombinant anti-m scFv-fused mutant actinoporin-like-toxin-1 (mHALT-1) immunotoxin that is capable of recognizing and eradicating codon-12 mutated k-ras antigen abnormal cells. Read More

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Targeting Cancer Stem Cells-A Renewed Therapeutic Paradigm.

Oncol Hematol Rev 2017 23;13(1):45-55. Epub 2017 May 23.

Department of Pathology, Beth Israel Deaconess Cancer Center and Harvard Medical School, Boston, Massachusetts, US; Harvard Stem Cell Institute, Cambridge, Massachusetts, US; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, US.

Metastasis is often accompanied by radio- and chemotherapeutic resistance to anticancer treatments and is the major cause of death in cancer patients. Better understanding of how cancer cells circumvent therapeutic insults and how disseminated cancer clones generate life-threatening metastases would therefore be paramount to the development of effective therapeutic approaches for clinical management of malignant disease. Mounting reports over the past two decades have provided evidence for the existence of a minor population of highly malignant cells within liquid and solid tumors, which are capable of self-renewing and of regenerating secondary growths with the heterogeneity of the primary tumors from which they derive. Read More

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Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer.

Front Pharmacol 2021 20;12:643492. Epub 2021 Apr 20.

Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland.

An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or long-term relief and are often associated with fatal complications. Allowing localized chemotherapy, by direct and confined drug delivery only at the tumor site, could be a promising option for preoperative down staging or palliative therapy. Read More

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Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition.

Nat Med 2021 May 6. Epub 2021 May 6.

UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality. Read More

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Integrase-derived peptides together with CD24-targeted lentiviral particles inhibit the growth of CD24 expressing cancer cells.

Oncogene 2021 May 6. Epub 2021 May 6.

Health Promotion Center and Integrated Cancer Prevention Center, Sourasky Medical Center, Tel-Aviv, Israel.

The integration of viral DNA into the host genome is mediated by viral integrase, resulting in the accumulation of double-strand breaks. Integrase-derived peptides (INS and INR) increase the number of integration events, leading to escalated genomic instability that induces apoptosis. CD24 is a surface protein expressed mostly in cancer cells and is very rarely found in normal cells. Read More

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Targeting non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex improves the efficacy of HEDGEHOG pathway inhibition in melanoma.

Oncogene 2021 May 6. Epub 2021 May 6.

Core Research Laboratory - Institute for Cancer Research and Prevention (ISPRO), Florence, Italy.

Despite the development of new targeted and immune therapies, the prognosis of metastatic melanoma remains bleak. Therefore, it is critical to better understand the mechanisms controlling advanced melanoma to develop more effective treatment regimens. Hedgehog/GLI (HH/GLI) signaling inhibitors targeting the central pathway transducer Smoothened (SMO) have shown to be clinical efficacious in skin cancer; however, several mechanisms of non-canonical HH/GLI pathway activation limit their efficacy. Read More

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Neuron replating - a powerful and versatile approach to study early aspects of neuron differentiation.

eNeuro 2021 May 6. Epub 2021 May 6.

Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, Germany

Neuron differentiation includes formation and outgrowth of neurites that differentiate into axons or dendrites. Directed neurite outgrowth is controlled by growth cones that protrude and retract actin-rich structures to sense environmental cues. These cues control local actin filament dynamics, steer growth cones towards attractants and away from repellents and navigate neurites through the developing brain. Read More

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ACR Appropriateness Criteria® Asymptomatic Patient at Risk for Coronary Artery Disease: 2021 Update.

J Am Coll Radiol 2021 May;18(5S):S2-S12

Specialty Chair, UT Southwestern Medical Center, Dallas, Texas.

Coronary atherosclerotic disease is a leading cause of mortality and morbidity due to major cardiovascular events in the United States and abroad. Risk stratification and early preventive measures can reduce major cardiovascular events given the long latent asymptomatic period. Imaging tests can detect subclinical coronary atherosclerosis and aid initiation of targeted preventative efforts based on patient risk. Read More

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ACR Appropriateness Criteria® Radiologic Management of Lower Gastrointestinal Tract Bleeding: 2021 Update.

J Am Coll Radiol 2021 May;18(5S):S139-S152

Specialty Chair, University of Chicago Hospital, Chicago, Illinois.

Diverticulosis remains the commonest cause for acute lower gastrointestinal tract bleeding (GIB). Conservative management is initially sufficient for most patients, followed by elective diagnostic tests. However, if acute lower GIB persists, it can be investigated with colonoscopy, CT angiography (CTA), or red blood cell (RBC) scan. Read More

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Sex differences in the association between maternal depression and child and adolescent cognitive development: a systematic review and meta-analysis.

Psychol Med 2021 May 7:1-10. Epub 2021 May 7.

Department of Social and Preventive Medicine, Université de Montréal, 7101 Avenue Parc, Montréal, Canada.

Background: Maternal depression is negatively associated with cognitive development across childhood and adolescence, with mixed evidence on whether this association differs in boys and girls. Herein, we performed a systematic review and meta-analysis of sex-specific estimates of the association between maternal depression and offspring cognitive outcomes.

Method: Seven databases (PubMed, EMBASE, PsycINFO, ERIC, CINAHL, Scopus, ProQuest) were searched for studies examining the longitudinal association between maternal depression and offspring (up to 18 years) cognitive outcomes. Read More

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Pathophysiological roles of myristoylated alanine-rich C-kinase substrate (MARCKS) in hematological malignancies.

Biomark Res 2021 May 6;9(1):34. Epub 2021 May 6.

Laboratory medicine program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada.

The myristoylated alanine-rich C-kinase substrate (MARCKS) protein has been at the crossroads of multiple signaling pathways that govern several critical operations in normal and malignant cellular physiology. Functioning as a target of protein kinase C, MARCKS shuttles between the phosphorylated cytosolic form and the unphosphorylated plasma membrane-bound states whilst regulating several molecular partners including, but not limited to calmodulin, actin, phosphatidylinositol-4,5-bisphosphate, and phosphoinositide-3-kinase. As a result of these interactions, MARCKS directly or indirectly modulates a host of cellular functions, primarily including cytoskeletal reorganization, membrane trafficking, cell secretion, inflammatory response, cell migration, and mitosis. Read More

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Current and emerging therapies for primary central nervous system lymphoma.

Biomark Res 2021 May 6;9(1):32. Epub 2021 May 6.

Department of Hematology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Read More

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Formulation Development and Improved Stability of a Combination Measles and Rubella Live-Viral Vaccine Dried for Use in the Nanopatch Microneedle Delivery System.

Hum Vaccin Immunother 2021 May 6:1-16. Epub 2021 May 6.

Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.

Measles (Me) and rubella (Ru) viral diseases are targeted for elimination by ensuring a high level of vaccination coverage worldwide. Less costly, more convenient MeRu vaccine delivery systems should improve global vaccine coverage, especially in low - and middle - income countries (LMICs). In this work, we examine formulating a live, attenuated Me and Ru combination viral vaccine with Nanopatch™, a solid polymer micro-projection array for intradermal delivery. Read More

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Classes of drugs that target the cellular components of inflammation under clinical development for COPD.

Expert Rev Clin Pharmacol 2021 May 6. Epub 2021 May 6.

Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.

Introduction: : The persistent inflammation that characterizes COPD and affects its natural course also impacting on symptoms has prompted research to find molecules that can regulate the inflammatory process but still available anti-inflammatory therapies provide little or no benefit in COPD patients. Consequently, numerous anti-inflammatory molecules that are effective in animal models of COPD have been or are being evaluated in humans.

Areas Covered: : In this article we describe several classes of drugs that target the cellular components of inflammation under clinical development for COPD. Read More

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Detection of exon 14 skipping mutations in non-small cell lung cancer: overview and community perspective.

Expert Rev Anticancer Ther 2021 May 7. Epub 2021 May 7.

Department of Pathology, Saint Luke's Health System of Kansas City, MAWD Pathology Group, Lenexa, Kansas, USA.

: Non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer diagnoses in the United States, has many known driver mutations, including exon 14 skipping mutation (ex14). The detection of oncogenic driver mutations in NSCLC and the development of drugs to target these alterations, including ex14, has created the need for accurate and reliable testing, of which next-generation sequencing (NGS) is the gold standard. However, detection of ex14 in patients with NSCLC can be challenging due to the complex biology of ex14 and the abilities of different NGS platforms to detect ex14. Read More

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A sample selection method specific to unknown test samples for calibration and validation sets based on spectra similarity.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Apr 24;258:119870. Epub 2021 Apr 24.

School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:

As is known to all, the construction of calibration and validation sets is of great importance for how to select representative samples into subsets so that the calibration model can be built, evaluated and predicted effectively for model development. In this study, a method was proposed for the calibration and validation sets constructed by selecting samples maximally similar to the test samples based on the spectra data. Both the Euclidean distance and Mahalanobis distance were attempted to estimate the spectra similarity. Read More

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