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Patient-Derived Organoids Can Guide Personalized-Therapies for Patients with Advanced Breast Cancer.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstr

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… Tissue samples from the other hospitals were placed on ice in DMEM (GIBCO) supplemented with 10% FBS (GIBCO), 100 units mL −1 penicillin (GIBCO), and 100 µg mL −1 streptomycin (GIBCO) and transported to the laboratory within 6 h. …

m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis.

BackgroundMETTL3 is an RNA methyltransferase that mediates m6A modification and is implicated in mRNA biogenesis, decay, and translation. However, the biomechanism through which METTL3 regulates MALAT1-miR-1914-3p-YAP axis activity to induce NSCLC drug resistance and metastasis is not very clear.MethodsThe expression of mRNA was analyzed by qPCR assays. Protein levels were analyzed by western blotting and immunofluorescent staining. Cellular proliferation was detected by CCK8 assays. Cell migration and invasion were analyzed by wound healing and transwell assays, respectively. Promoter activit

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… Cell lines were cultivated in RPMI-1640 medium supplemented with 10% FBS (Hyclone, USA), penicillin/streptomycin (100 mg/mL). Culture flasks were kept at 37 °C in a humid incubator with 5% CO 2 . …

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming.

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiatio

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… Cells were cultured in RPMI 1640 with GlutaMAX (Thermo Fisher Scientific) supplemented with 10% fetal bovine serum (Cambrex BioScience), 100 U/ml penicillin and 100 μg/ml streptomycin. Cultures were maintained at 37°C in a humidified atmosphere containing 5% CO 2 . …

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, trigg

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… Cell lines and treatments Cell lines derived from HNCs of the tongue (SCC-15, CAL-27), pharynx (FaDu) or salivary gland (A-253) were from ATCC (Manassas, VA, USA) and maintained in RPMI containing 10% fetal bovine serum, 100 U/ml penicillin, and 100 μg/ml streptomycin. …

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes.

Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with parado

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… TIB-152 ™ USA, S2 Fig ) were cultured in T75 flasks (Falcon Labware Becton Dickinson (BD) Biosciences, Oxnard, CA) in complete RPMI 1640 medium (GIBCO/BRL, Invitrogen, Gaithersburg, CA) supplemented with 10% FBS (Hyclone, South Logan, UT), L-glutamine (2 mM, EuroClone Milan, Italy) and 1% penicillin/streptomycin …

Development of a machine learning-based predictive risk model combining fatty acid metabolism and ferroptosis for immunotherapy response and prognosis in prostate cancer.

Prostate cancer (PCa) remains a leading cause of cancer-related mortality, necessitating robust prognostic models and personalized therapeutic strategies. This study integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to construct a prognostic model based on genes shared between ferroptosis and fatty acid metabolism (FAM). Using the TCGA-PRAD dataset, we identified 73 differentially expressed genes (DEGs) at the intersection of ferroptosis and FAM, of which 19 were significantly associated with progression-free survival (PFS). A machine learning-

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… Detection the levels of C11-BODIPY, Fe 2+ , and ROS in cells overexpressing CD38 via flow cytometry PCa cell line of PC-3 cells (Procell, Wuhan, China) are cultured in RPMI-1640 medium (Thermofisher, Massachusetts, USA) with 10% FBS (Thermofisher, Massachusetts, USA) and 1% Penicillin–Streptomycin ( …

USP14 inhibition by degrasyn induces YAP1 degradation and suppresses the progression of radioresistant esophageal cancer.

BACKGROUND: Radiotherapy is a major modality for esophageal cancer (ESCA) treatment, yet radioresistance severely hampers its therapeutic efficacy. Ubiquitin-specific peptidase 14 (USP14) is a novel deubiquitinase and can mediate cancer cells' response to irradiation, although the underlying mechanism remains unclear, including in ESCA. METHODS: To evaluate the expression of USP14 in ESCA tissues or cells, we used RNA-Seq, immunoblotting, co-immunoprecipitation (Co-IP), ubiquitination, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence assays in this investigat

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… All cell lines were grown in RPMI-1640 or DMEM culture medium (Gibco, Carlsbad, CA, USA) supplemented with 10 % fetal bovine serum (FBS, Gibco, USA), 100 U/mL penicillin, and 100 mg/mL streptomycin (Procell, Wuhan, China) in a humidified incubator at 37°C with 5 % CO 2 . …

Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response.

Alpha-ketoglutarate (αKG) emerged as a key regulator of energetic and redox metabolism in cells, affecting the immune response in various conditions. However, it remained unclear how the exogenous αKG modulates the functions of dendritic cells (DCs), key cells regulating T-cell response. Here we found that non-toxic doses of αKG display anti-inflammatory properties in human APC-T cell interaction models. In a model of monocyte-derived (mo)DCs, αKG impaired the differentiation, and the maturation of moDCs induced with lipopolysaccharide (LPS)/interferon (IFN)-γ, and decreased their capacity to

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… Louis, Missouri, USA), and antibiotics (Penicillin and Streptomycin, 100U/ml, Merk Sigma). α-Ketoglutaric acid disodium salt dihydrate (α-KG, Millipore Sigma, Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany) stock solution (1M) was prepared fresh in Dulbecco Modified Eagle Medium without L-glutamine …

Неверный перевод из эндогенного варианта ТРНА в пангеномных линиях клеток человека.

Варианты антикодона для передачи человека RNA (tRNA) являются источником ошибки перевода. :: tRNASerAGA-2-3 Вариант (G35A) 2% популяции человека и приводит к неправильной инкорпорации серин в фениланинских кодонах. Здесь мы разработали двойной флуоресцентный репортер для количественной оценки уровней неправильной инкорпорации в живых человеческих и муринных клетках и подтвердили неправильную трансляцию с помощью масс-спектрометрии. В β-лимфоцитах от отдельных лиц 1000 Проект по геномам, мы подтвердили предполагаемый генотип клеток с маленькими аллеями A35, и последовательность tRNA продемонстр

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… Plasmid transfection HEK 293T, K562, and N2a mammalian cells were cultured in Dulbecco’s modified Eagle medium (DMEM 4.5 g/l; Gibco) with 10% fetal bovine serum (FBS; Gibco, Thermo Fisher Scientific, Waltham, MA, United States) and 1% streptomycin–penicillin (S/P) (Wisent Bioproducts, St. …

Metabolism-related ALDH1B1 acts as potential predictor and therapeutic target for primary gastrointestinal diffuse large B-cell lymphoma.

Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is the most common extra-nodal DLBCL. Metabolism-related factors have been associated with tumor progression, but the relationship between abnormal metabolism and prognosis of PGI-DLBCL remains unelucidated. In our study, consensus clustering based on metabolism-related genes classified PGI-DLBCL patients into two metabolic subtypes, and poor prognosis was associated with immunosuppressive microenvironment. A prognostic signature based on five metabolism-related genes (APOE, ALDH6 A1, PLOD2, IKBKB and ALDH1B1) was developed. Pa

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… OCI-LY1 (RRID: CVCL_1879) and OCI-LY3 (RRID: CVCL_8800) cells were purchased from ATCC, cultured in IMDM (Gibco, CA, USA) supplemented with 10% fetal bovine serum (HyClone, UT, USA), 1% penicillin/streptomycin mixture, and 2 mM glutamine, and incubated at 37 °C in humidified air containing 5% CO2. …

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.

The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin-proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and c

Frentizole, a Nontoxic Immunosuppressive Drug, and Its Analogs Display Antitumor Activity via Tubulin Inhibition.

Antimitotic agents are one of the more successful types of anticancer drugs, but they suffer from toxicity and resistance. The application of approved drugs to new indications (i.e., drug repurposing) is a promising strategy for the development of new drugs. It relies on finding pattern similarities: drug effects to other drugs or conditions, similar toxicities, or structural similarity. Here, we recursively searched a database of approved drugs for structural similarity to several antimitotic agents binding to a specific site of tubulin, with the expectation of finding structures that could f

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… Louis, MO, USA), 2 mM L-glutamine, 100 μg/mL streptomycin, and 100 units/mL penicillin (Gibco, Waltham, MA, USA) at 37 °C in humidified 95% air and 5% CO 2 . …

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchy

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… Cell suspensions (1.0–2.5 ×10 3 cells/cm 2 ) were incubated at 37°C and 5% CO 2 in Advanced MEM with 5% platelet lysate, PLTMax (MillCreek LifeSciences), 2 U/ml heparin (Novaplus), 2 mM L-glutamine (Invitrogen) and antibiotics (100 U/ml penicillin, 100 g/ml streptomycin, Sigma). …

Мукоадгезивные наноэмульсии для доставки нозы в мозг диметилфумарат: разработка, характеристика и доказательство согласия

Фон. Диметилфумарат (ДМП) является утвержденным терапевтическим агентом для лечения множественного склероза, известным своими противовоспалительными и нейрозащитными свойствами. Однако его пероральное управление часто сопровождается побочными эффектами желудочно-кишечного кишечника, что ограничивает его терапевтический потенциал. В настоящем исследовании была разработана новая формула наноэмульсии (NE), которая была охарактеризована с целью усиления воздействия ДМП в цереброспинарной жидкости (CSF) после внутринационального администрирования. Методы: Состав был подготовлен методом самоэмульсиф

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… Cell maintenance was performed in αMEM medium (PAN Biotech, Aidenbach, Germany), supplemented with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 1% glutamine, and 1% penicillin-streptomycin-amphotericin [ 53 ]. …

In Vivo and In Vitro Pharmacokinetic Studies of a Dual Topoisomerase I/II Inhibitor.

Due to high mortality rates, new and more effective drugs are urgently needed in cancer therapy. The novel dual topoisomerase inhibitor P8-D6, a dimethylaminoethyl-substituted pyridophenanthroline, showed in vitro impressive induction of apoptosis in tumors such as ovarian cancer or multiple myeloma compared to the current standard therapy. The purpose of this study was to investigate its in vitro and in vivo pharmacokinetics and to discover further potential drug candidates. Samples of plasma, various tissues, urine, feces, and cell culture supernatants were examined by HPLC. In addition, the

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… Cell Culture The human ovarian cancer cell lines OvCar8, Igrov-1, and A2780, purchased from ATCC, were maintained in RPMI1640 medium, including l -glutamine supplemented with 10% fetal bovine serum and 60 IU/mL penicillin–streptomycin. …

Parasites' immunomodulators: a breakthrough in immunotherapeutics displaying antineoplastic activity against human colorectal and hepatocellular carcinoma cells.

The complex interplay between parasites and cancer is yielding promising advances in the field of cancer therapeutics. This study explored the in vitro anti-cancer potential of parasite immunomodulators (antigens and antibodies) of Schistosoma mansoni, Trichinella spiralis, and Toxoplasma gondii on human HT-29 colorectal and HepG2 hepatocellular carcinoma cells using the MTT assay. Results revealed that those parasites' immunomodulators exhibited antineoplastic activity and demonstrated a statistically significant inhibition of both cancer cell lines' proliferation (P ˂0.05). Notably, Trichine

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… Mycoplasma -free cancer cells were cultured in high glucose Dulbecco’s Modified Eagle Medium (DMEM) (Sigma-Aldrich) supplemented with 10% fetal bovine serum (Sigma-Aldrich), 2 mM L-glutamine (Thermo Fisher Scientific), 1 mM sodium pyruvate (Fisher Scientific), Streptomycin (100 mg/ml) (Thermo Fisher …

Клетки T-бет+CXCR3+B вызывают гиперреактивное взаимодействие клеток B-T в множестве склерозов.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS). Одним из ключевых механизмов в НР является автораспространение (АП) ячеек В и Т, основанное на самопропитании. Здесь мы показываем, что про-воспаление B-T-обогащенные клетки клеток (BTEC) формируются во время AP и зеркальные особенности реакции микроцентра. T-bet+CXCR3+B — основной подмножество клеток, усиливающих и поддерживающих свои параллельные клетки TH1 с помощью интерферона (IFN)-__, и присутствуют в сильно воспламенённой менингетной ткани. Фундаментальная сигнатура активации клеток В находит свое о

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… Thermo Fisher Scientific Cat# L10119 LIVE/DEAD™ Fixable Violet Dead Cell Stain Kit Thermo Fisher Scientific Cat# L34955 Maleimide Sigma-Aldrich Cat# 129585 Methanol Sigma Aldrich Cat# 322415 Paraformaldehyde, EM Grade, Purified (Polyoxymethylene) Electron Microscopy Sciences Cat# 15710 Penicillin/Streptomycin …

Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.

The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR action in myeloma. Here, we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that plays a role in improved myeloma cell killing. We show that the GR agonist dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the

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… Materials and methods Cell lines and reagents MM1.S, OPM-2, L-363, U-266 and MM1.R cells were cultured in RPMI1640 GlutaMAX and HEK293T and EA.hy926 cells in DMEM, both supplemented with 10% fetal bovine serum (FBS), 100U/mL penicillin and 0.1 mg/mL streptomycin and grown at 5% CO 2 and 37 °C. …

Epigenetic profiling reveals key super-enhancer networks driving oncogenesis in HPV-positive HNSCC.

Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is a growing subset of cancer cases distinct from HPV-negative by fewer genetic mutations and prevalent epigenetic dysregulation. We mapped H3K27ac-marked super-enhancers (SEs) via ChIP-seq in HPV+ patient-derived xenografts (PDXs) and normal oropharyngeal mucosa, identifying tumor-specific SE domains (T-SEDs) enriched for transcription factors (TFs) including TP63, FOSL1, and JUND. These SE-associated TFs regulate key oncogenic pathways and are downregulated by BRD4 inhibition with JQ1, highlighting sensitivity

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… culture and drug treatment Human HPV+ HNSCC cell lines UM-SCC-047 (RRID:CVCL_7759) and UPCI-SCC-090 (RRID:CVCL_1899) were grown on high-glucose DMEM media (Clontech, Mountain View, CA, Cat# 11965092), supplemented by 10% fetal bovine serum (FBS; Atlanta Biologicals, Cat# S11550H) and 1% Penicillin-Streptomycin …

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) ba

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… HEK293T Cell Culture, Infection, RNA Extraction, and qRT-PCR HEK293T cells ( CRL11268 ; ATCC/LGC standards) were cultured in DMEM supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C in a 5% CO2/air atmosphere. …