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Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome.

Ren Fail 2022 Dec;44(1):923-932

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin.

Accumulating evidence has implicated that berberine (BBR) has a beneficial effect on diabetic kidney disease (DKD), but its mechanism is not clear. The aim of this study was to assess whether berberine could alleviate tubulointerstitial fibrosis and attenuate epithelial-to-mesenchymal transition (EMT) and its possible molecular mechanism. High-fat diet (HFD) followed by injection of STZ was used to induce diabetic rats . Read More

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December 2022

Mechanism of effective combination radio-immunotherapy against 9464D-GD2, an immunologically cold murine neuroblastoma.

J Immunother Cancer 2022 May;10(5)

Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA

Background: Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( ombination daptive- nnate immunotherapy egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. Read More

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Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial.

J Immunother Cancer 2022 May;10(5)

Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Cancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP. Read More

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Transcriptome analysis of CRISPR/Cas9-mediated GPAM in bovine mammary epithelial cell-line unravelled the effects of GPAM gene on lipid metabolism.

Gene 2022 May 23:146574. Epub 2022 May 23.

College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, Guangdong, 524088, P.R.China. Electronic address:

Glycerol-3-phosphate acyltransferase mitochondrial (GPAM) is an enzyme in animal lipid metabolism pathways that catalyzes the initial and most committed step of glycerolipid biosynthesis. The present study mainly focused on exploring the relationship between the GPAM gene and the lipid metabolism of mammary epithelial cells and the effect of GPAM on the related pathways of lipid metabolism. The GPAM gene was knocked out entirely in bovine mammary epithelial cells(BMECs) using CRISPR/Cas9 technology, and the mechanism by which the GPAM gene regulates lipid metabolism in BMECs was confirmed. Read More

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Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer.

Clin Immunol 2022 May 23:109045. Epub 2022 May 23.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China. Electronic address:

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Read More

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Synthesis, biological evaluation and mechanism studies of C-3 substituted nitrogenous heterocyclic 23-Hydroxybetulinic acid derivatives as anticancer agents.

Fitoterapia 2022 May 23:105222. Epub 2022 May 23.

College of Materials & Chemical Engineering, Chuzhou University, 1 West Huifeng Road, Chuzhou 239000, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address:

A series of novel nitrogenous heterocycle substituted 23-Hydroxybetulinic acid (23-HBA) derivatives with amide linkages at the C-3 position were designed, synthesized and evaluated for their antitumor activities. The biological screening results showed that most of the derivatives exhibited more potent antiproliferative activities than 23-HBA. In particular compound II-9 exhibited the most potent activities with IC values ranging from 1. Read More

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PROPHYLACTIC EFFECT OF NITRIC OXIDE DONORS ON RAT MODELS OF EGFR INHIBITORS-INDUCED CUTANEOUS TOXICITIES.

J Invest Dermatol 2022 May 23. Epub 2022 May 23.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China. Electronic address:

Epidermal growth factor receptor inhibitors (EGFRIs) have been established as first-line standard-of-care therapies for non-small cell lung cancer (NSCLC) but are frequently accompanied by adverse dermatological effects, in particular, acneiform rash. There is no effective clinical intervention, partially because of its poorly understood etiology. Here, we show that inhibition of EGFR initiated keratinocyte HaCaT cell cycle arrest and apoptosis, which fueled a robust secondary inflammatory response. Read More

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Engineered colorectal cancer tissue recapitulates key attributes of a patient-derived xenograft tumor line.

Biofabrication 2022 May 26. Epub 2022 May 26.

Department of Chemical Engineering Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL 36849-5127 , USA, Auburn, Alabama, 36849-5412, UNITED STATES.

The development of physiologically relevant in vitro colorectal cancer (CRC) models is vital for advancing understanding of tumor biology. Although CRC patient-derived xenografts (PDX) recapitulate key patient tumor characteristics and demonstrate high concordance with clinical outcomes, the use of this in vivo model is costly and low-throughput. Here we report the establishment and in-depth characterization of an in vitro tissue-engineered CRC model using PDX cells. Read More

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Generation of a human extended pluripotent stem cell line (SKLRMe002-A) carrying a doxycycline-inducible Cas9 expression cassette.

Stem Cell Res 2022 May 17;62:102816. Epub 2022 May 17.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. Electronic address:

Human extended pluripotent stem cell (hEPS) is a novel type of pluripotent stem cell, which possesses bi-potency towards both embryonic and extraembryonic lineages. Here, we generated a hEPS cell line (hEPS1-iCas9-B) from the cell line named hEPS1, carrying a doxycycline-inducible Cas9 expression cassette along with a constitutive reverse tetracycline transactivator (M2rtTA) expression cassette at the AAVS1 locus, thus we could efficiently generate genetically modified hEPS for studies. This cell lined remained self-renewal, differentiation potential and normal karyotype. Read More

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Generation of isogenic control DJ-1-delP GC13 for the genetic Parkinson's disease-patient derived iPSC line DJ-1-delP (LCSBi008-A-1).

Stem Cell Res 2022 May 17;62:102815. Epub 2022 May 17.

Translational Neuroscience, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg; Parkinson Research Clinic, Centre Hospitalier de Luxembourg (CHL), Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Luxembourg. Electronic address:

We describe the generation of an isogenic control cell line DJ-1-delP GC13 from an induced pluripotent stem cell (iPSC) line DJ-1-delP LCSBi008-A that was derived from fibroblasts obtained from a Parkinson's disease (PD) patient. Using CRISPR/Cas9 technology, we corrected the disease causing c.471_473delGCC homozygous mutation in the PARK7 gene leading to p. Read More

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Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models.

Biomed Pharmacother 2022 May 23;151:113163. Epub 2022 May 23.

Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo, FG, Italy. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The characteristic excessive stromatogenesis accompanying the growth of this tumor is believed to contribute to chemoresistance which, together with drug toxicity, results in poor clinical outcome. An increasing number of studies are showing that gut microbiota and their metabolites are implicated in cancer pathogenesis, progression and response to therapies. Read More

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A pH-sensor scaffold for mapping spatiotemporal gradients in three-dimensional in vitro tumour models.

Biosens Bioelectron 2022 May 18;212:114401. Epub 2022 May 18.

Institute of Nanotechnology, National Research Council (CNR-NANOTEC), c/o Campus Ecotekne, via Monteroni, 73100, Lecce, Italy. Electronic address:

The detection of extracellular pH at single cell resolution is challenging and requires advanced sensibility. Sensing pH at high spatial and temporal resolution might provide crucial information in understanding the role of pH and its fluctuations in a wide range of physio-pathological cellular processes, including cancer. Here, a method to embed silica-based fluorescent pH sensors into alginate-based three-dimensional (3D) microgels tumour models, coupled with a computational method for fine data analysis, is presented. Read More

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LRP4-IgG service line testing in seronegative myasthenia gravis and controls.

J Neuroimmunol 2022 May 18;368:577895. Epub 2022 May 18.

Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, MN, USA. Electronic address:

Background: LRP4 is a post-synaptic membrane protein that promotes acetylcholine (AChR) clustering on the crest of post-synaptic neuromuscular folds. Autoantibodies against LRP4 are suggested to account for myasthenia gravis (MG) patients negative for antibodies to AChR.

Objectives: To report a clinical experience with service-line LRP4-IgG cell-based testing in electrodiagnostically confirmed MG patients and controls. Read More

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A New Transgenic Line for Rapid and Complete Neutrophil Ablation.

Zebrafish 2022 May 26. Epub 2022 May 26.

School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.

Zebrafish lines expressing nitroreductase (NTR) in specific cell compartments, which sensitizes those cells to metronidazole (MTZ)-mediated ablation, have proven extremely useful for studying tissue regeneration and investigating cell function. In contrast to many cells, neutrophils are comparatively resistant to the NTR/MTZ targeted ablation strategy. Recently, a rationally engineered variant of NTR (NTR 2. Read More

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Formulation and Characterization of Raloxifene Nanostructured Lipid Carriers for Permeability and Uptake Enhancement Applications.

Assay Drug Dev Technol 2022 May 26. Epub 2022 May 26.

Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA.

Raloxifene (RLX), a biopharmaceutical classification system (BCS) class II drug, is a selective estrogen receptor modulator (SERM) having an estrogenic effect on the bone and an antiestrogenic effect on the endometrium and breast. Low solubility, high permeability, high metabolism, and low bioavailability are the characteristics of raloxifene. Although 60% is absorbed orally, raloxifene shows extremely poor bioavailability (2%) owing to its low solubility and extensive (>90%) intestinal/hepatic first-pass metabolism. Read More

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Phytochemical characterisation, antioxidant capacity, and toxicity of gomes crude extracts.

Nat Prod Res 2022 May 26:1-5. Epub 2022 May 26.

Postgraduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.

is a species used in folk medicine and rich in active compounds. In this study, the extracts were submitted to UHPLC-ESI-MS/MS analysis and total polyphenols, tannins, and flavonoids assays. Besides, it was determined its antioxidant capacity, oxidative stress markers and toxicological profile. Read More

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Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets.

Science 2022 May 27;376(6596):eabe1505. Epub 2022 May 27.

Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.

In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing to investigate 22 organoids, six patient-derived xenografts, and 12 cell lines. We identified the well-characterized AR-dependent and neuroendocrine subtypes, as well as two AR-negative/low groups: a Wnt-dependent subtype, and a stem cell-like (SCL) subtype driven by activator protein-1 (AP-1) transcription factors. Read More

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Increased expression of SPRR1A is associated with a poor prognosis in pancreatic ductal adenocarcinoma.

PLoS One 2022 26;17(5):e0266620. Epub 2022 May 26.

Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Hyogo, Japan.

Objectives: Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC. Read More

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Use of CRISPR/Cas9 with homology-directed repair to silence the human topoisomerase IIα intron-19 5' splice site: Generation of etoposide resistance in human leukemia K562 cells.

PLoS One 2022 26;17(5):e0265794. Epub 2022 May 26.

Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States of America.

DNA Topoisomerase IIα (TOP2α/170) is an enzyme essential for proliferating cells. For rapidly multiplying malignancies, this has made TOP2α/170 an important target for etoposide and other clinically active anticancer drugs. Efficacy of these agents is often limited by chemoresistance related to alterations in TOP2α/170 expression levels. Read More

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Potential of phenothiazines to synergistically block calmodulin and reactivate PP2A in cancer cells.

PLoS One 2022 26;17(5):e0268635. Epub 2022 May 26.

Cancer Cell Biology and Drug Discovery Group, Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Phenothiazines (PTZ) were developed as inhibitors of monoamine neurotransmitter receptors, notably dopamine receptors. Because of this activity they have been used for decades as antipsychotic drugs. In addition, they possess significant anti-cancer properties and several attempts for their repurposing were made. Read More

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Involvement of a putative ATP-Binding Cassette (ABC) Involved in manganese transport in virulence of Listeria monocytogenes.

PLoS One 2022 26;17(5):e0268924. Epub 2022 May 26.

Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Wyndmoor, PA, United States of America.

Listeria monocytogenes is a foodborne pathogen and the causative agent of listeriosis, a disease associated with high fatality (20-30%) and hospitalization rates (>95%). ATP-Binding Cassette (ABC) transporters have been demonstrated to be involved in the general stress response. In previous studies, in-frame deletion mutants of the ABC transporter genes, LMOf2365_1875 and LMOf2365_1877, were constructed and analyzed; however, additional work is needed to investigate the virulence potential of these deletion mutants. Read More

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Acquired chemoresistance drives spatial heterogeneity, chemoprotection and collective migration in pancreatic tumor spheroids.

PLoS One 2022 26;17(5):e0267882. Epub 2022 May 26.

Cornell University, Ithaca, New York, United States of America.

Tumors display rich cellular heterogeneity and typically consist of multiple co-existing clones with distinct genotypic and phenotypic characteristics. The acquisition of resistance to chemotherapy has been shown to contribute to the development of aggressive cancer traits, such as increased migration, invasion and stemness. It has been hypothesized that collective cellular behavior and cooperation of cancer cell populations may directly contribute to disease progression and lack of response to treatment. Read More

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A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models.

PLoS Biol 2022 May 26;20(5):e3001624. Epub 2022 May 26.

Oncology Safety, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Boston, Massachusetts, United States of America.

Test compounds used on in vitro model systems are conventionally delivered to cell culture wells as fixed concentration bolus doses; however, this poorly replicates the pharmacokinetic (PK) concentration changes seen in vivo and reduces the predictive value of the data. Herein, proof-of-concept experiments were performed using a novel microfluidic device, the Microformulator, which allows in vivo like PK profiles to be applied to cells cultured in microtiter plates and facilitates the investigation of the impact of PK on biological responses. We demonstrate the utility of the device in its ability to reproduce in vivo PK profiles of different oncology compounds over multiweek experiments, both as monotherapy and drug combinations, comparing the effects on tumour cell efficacy in vitro with efficacy seen in in vivo xenograft models. Read More

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Progesterone receptor expression contributes to gemcitabine resistance at higher ECM stiffness in breast cancer cell lines.

PLoS One 2022 26;17(5):e0268300. Epub 2022 May 26.

Department of Oncology and Metabolism, Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield, United Kingdom.

Chemoresistance poses a great barrier to breast cancer treatment and is thought to correlate with increased matrix stiffness. We developed two-dimensional (2D) polyacrylamide (PAA) and three-dimensional (3D) alginate in vitro models of tissue stiffness that mimic the stiffness of normal breast and breast cancer. We then used these to compare cell viability in response to chemotherapeutic treatment. Read More

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MicroRNA-7a-5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c-JUN pathway.

Diabet Med 2022 May 26:e14890. Epub 2022 May 26.

Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China.

Aims: The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA-7a-5p (miR-7a-5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR-7a-5p in DPN. Read More

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Sawhorse-type ruthenium complexes with triazolopyrimidine ligands - what do they represent in terms of cytotoxic and CORM compounds?

Dalton Trans 2022 May 26. Epub 2022 May 26.

Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, Lwowska 1, 87-100 Toruń, Poland.

Three sawhorse-type ruthenium(I) complexes containing purine analogs such as triazolopyrimidines of the general formula [Ru(CO)(μ-OOCCH)(L)], where L is 1,2,4-triazolo[1,5-]pyrimidine (tp for 1), 5,7-ditertbutyl-1,2,4-triazolo[1,5-]pyrimidine (dbtp for 2) and 5,7-diphenyl-1,2,4-triazolo[1,5-]pyrimidine (dptp for 3), have been synthesized and characterized by elemental analysis, infrared analysis, multinuclear magnetic resonance spectroscopic techniques (H, C, N), and single-crystal X-ray diffraction (for 1 and 2). By assay with myoglobin, the photo-activated CO-releasing molecule (PhotoCORM) character of (1-3) has been confirmed, thus indicating the possibility of use in CO-based therapies. The importance of UV-induced modification has been investigated in the context of anticancer properties. Read More

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AP-1 Subunit JUNB Promotes Invasive Phenotypes in Endometriosis.

Reprod Sci 2022 May 26. Epub 2022 May 26.

Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA.

Endometriosis is a disease defined by the presence of abnormal endometrium at ectopic sites, causing pain and infertility in 10% of women. Mutations in the chromatin remodeling protein ARID1A (AT-rich interactive domain-containing protein 1A) have been identified in endometriosis, particularly in the more severe deep infiltrating endometriosis and ovarian endometrioma subtypes. ARID1A has been shown to regulate chromatin at binding sites of the Activator Protein 1 (AP-1) transcription factor, and AP-1 expression has been shown in multiple endometriosis models. Read More

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Hsa_circ_0006732 regulates colorectal cancer cell proliferation, invasion and EMT by miR-127-5p/RAB3D axis.

Mol Cell Biochem 2022 May 26. Epub 2022 May 26.

The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, China.

Colorectal cancer (CRC) remains a malignancy tumor with high metastasis and poor prognosis. We aimed to explore the effect of circular RNA (circRNA) hsa_circ_0006732 in the progression of CRC. Hsa_circ_0006732 expression in CRC tissues and cell lines were detected using qRT-PCR. Read More

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The relationship between pan-immune-inflammation value and survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab in the second line and beyond: a Turkish oncology group kidney cancer consortium (TKCC) study.

J Cancer Res Clin Oncol 2022 May 26. Epub 2022 May 26.

Faculty of Medicine Department of Medical Oncology, Ankara University, Cebeci, 06590, Ankara, Turkey.

Background: Pan-immune-inflammation value (PIV) is an easily accessible immune marker based on peripheral blood to estimate prognosis in patients with cancer. This study evaluates the prognostic value of PIV in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.

Methods: In this retrospective cohort study, patients with mRCC treated with nivolumab in the second line and beyond were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Read More

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Apoptosis inducing metabolite from marine mangrove actinobacteria VITGAP173.

Anticancer Agents Med Chem 2022 May 23. Epub 2022 May 23.

Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore - 14, Tamil Nadu, India.

Background: Marine actinobacteria have proven to be a remarkable source of bioactive metabolites.

Methods: The present study focused on the isolation of anticancer metabolites from marine actinobacteria. Streptomyces sp. Read More

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