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Curcumol inhibits the malignant progression of prostate cancer and regulates the PDK1/AKT/mTOR pathway by targeting miR‑9.

Curcumol has been reported to exert anti‑tumor activity, but its intrinsic molecular mechanism in prostate cancer remains to be elucidated. The present study aimed to analyze the effect of curcumol on prostate cancer and identify its possible internal regulatory pathway using in vitro cell culture and in vivo tumor model experiments. The cytotoxicity of curcumol was detected using a Cell Counting Kit‑8 assay and it was found that curcumol had no obvious toxicity or side effects on RWPE‑1 cells. Wound healing, Transwell and flow cytometry assays demonstrated that curcumol could affect the activ

MSC Senescence-Related Genes Are Associated with Myeloma Prognosis and Lipid Metabolism-Mediated Resistance to Proteasome Inhibitors.

BackgroundComplex carcinogenic mechanisms and the existence of tumour heterogeneity in multiple myeloma (MM) prevent the most commonly used staging system from effectively interpreting the prognosis of patients. Since the microenvironment plays an important role in driving tumour development and MM occurs most often in middle-aged and elderly patients, we hypothesize that ageing of bone marrow mesenchymal stem cells (BM-MSCs) may be associated with the progression of MM.MethodsIn this study, we collected the transcriptome data on MM from The Cancer Genome Atlas (TCGA) and the Gene Expression O

Hemostatic and platelet proteins are associated with bleeding grade and time to major bleed in hemato-oncological patients.

Bleeding crises are common complications in hemato-oncological patients undergoing chemotherapy and stem cell transplantation. Platelet transfusions are frequently administered to treat and prevent bleeding events at low platelet counts. However, the association between thrombocytopenia and bleeding events remains unclear, arguing for an improved understanding of pathophysiological changes underpinning bleeding events. Therefore, this study aims to identify plasma protein levels associated with bleeding events in a hemato-oncological patient population using unbiased mass spectrometry-based pl

Свет в диагностике, терапии и хирургии.

Легкие и оптические методы оказывают глубокое воздействие на современную медицину, и в настоящее время в клинической практике используются многочисленные лазеры и оптические устройства для оценки состояния здоровья и лечения заболеваний. Последние достижения в области биомедицинской оптики позволили использовать все более сложные технологии, в частности технологии, которые объединяют фотонику с нанотехнологией, биоматериалами и генной инженерией. В настоящем Обзоре мы вновь обращаемся к основам взаимодействия легкой материи, описываем применение света в визуализации, диагностике, терапии и хир

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… For example, when a laser beam with a short penetration depth of 100 μm is illuminated over an area of 1 cm 2 , a fluence of 1 J/cm 2 will raise the temperature of the tissue surface by 25 °C above body temperature (62 °C), at which protein denaturation occurs. … The peak temperature at which irreversible tissue damage occurs depends on exposure time: according to the Arrhenius model 236 , protein denaturation is induced at 60 °C for τ=1 s but requires 90 °C for τ=10 ns. …

Tubulin binding potentially clears up Bortezomib and Carfilzomib differential neurotoxic effect.

Proteasome inhibitors (PIs) represent the gold standard in the treatment of multiple myeloma. Among PIs, Bortezomib (BTZ) is frequently used as first line therapy, but peripheral neuropathy (PN), occurring approximately in 50% of patients, impairs their life, representing a dose-limiting toxicity. Carfilzomib (CFZ), a second-generation PI, induces a significantly less severe PN. We investigated possible BTZ and CFZ off-targets able to explain their different neurotoxicity profiles. In order to identify the possible PIs off-targets we used the SPILLO-PBSS software that performs a structure-base

Porphyromonas gingivalis усугубляет экспериментальный аутоиммунный энцефаломиэлит, проводя дифференциацию TH1 с помощью сигнала ZAP70/NF-IB.

Множественный склероз (MS) характеризуется хроническим воспалением и обезвоживанием в центральной нервной системе (CNS), главным образом в результате ненормальной активации периферической иммунной системы, в частности клеток TH1. Как основной патоген в периодонтрите, Porphyromonas gingivalis (P. gingivalis) связан с повышенным риском множественных склерозных прогрессий; однако его роль в центральной нервной системе воспаления остается неясной. В этом исследовании мы стремились определить, поощряет ли P. gingivalis периферическую дифференциацию клеток TH1 по сигнальному маршруту ZAP70/NF-InB, т

Drug prioritization identifies panobinostat as a tailored treatment element for patients with metastatic hepatoblastoma.

BACKGROUND: Patients with metastatic hepatoblastoma are treated with severely toxic first-line chemotherapies in combination with surgery. Yet, inadequate response of lung metastases to neo-adjuvant chemotherapy still compromises patient outcomes making new treatment strategies, tailored to more efficient lung clearance, mandatory. METHODS: We harnessed a comprehensive patient-derived xenograft platform and a variety of in vitro and in vivo assays to establish the preclinical and biological rationale for a new drug for patients with metastatic hepatoblastoma. RESULTS: The testing of a librar

Nanomedicine Meets Immunotherapy: Advancing Adoptive Cell Therapy with Nanoparticles in the Treatment of Cancer with Sustainability Perspectives.

Immunotherapy has achieved remarkable clinical success in certain cancers, particularly through adoptive cell therapy (ACT), where T cell engineering with chimeric antigen receptor (CAR) has driven major clinical breakthroughs in the treatment of hematologic malignancies. However, efficacy against solid tumors remains limited due to multiple barriers, including the scarcity of tumor-specific antigens, antigen heterogeneity, immunosuppressive tumor microenvironment, and physical obstruction of T cell infiltration by dense extracellular matrix. Nanoparticle (NP)-based approaches can overcome the

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… These elevated temperatures are typically maintained for only a few minutes, which is sufficient to induce protein denaturation, membrane disruption, and vascular occlusion [ 183 , 189 , 191 ]. … Increasing the temperature further, up to 60°C, leads to nearly instantaneous cell death due to protein denaturation and melting of the plasma membrane [ 189 ]. FIGURE 6 Intracellular effects of mild hyperthermia in cancer cells. …

Aqueous Extract of Cimicifuga dahurica Reprogramming Macrophage Polarization by Activating TLR4-NF-κB Signaling Pathway.

PurposeCimicifuga dahurica (C. dahurica), which has been used in traditional oriental medicine for a long period, was reported to exert extensive antitumor activity, but the effect and molecular biological mechanism of C. dahurica on multiple myeloma (MM) has not been elaborated. Tumor-associated macrophages (TAMs) exhibit a sustained polarization between tumor killing M1 subtype and tumor supporting M2 subtype. And a lower ratio of M1/M2 is associated with tumor angiogenesis, proliferation and invasion. We explored the inhibitory effect of the aqueous extract of the root of C. dahurica (CRAE)

The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease.

Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone di

The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear fac

Recent advances in renal transplantation: antibody-mediated rejection takes center stage.

Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. Th

CeRNA Expression Profiling Identifies KIT-Related circRNA-miRNA-mRNA Networks in Gastrointestinal Stromal Tumour.

Gastrointestinal stromal tumours (GISTs) are the most common human sarcomas and are typically located in the stomach or small intestine. Although circular RNAs (circRNAs) reportedly play vital roles in tumour oncogenesis and progression, the molecular basis of the aggressive tumour biology of these circRNAs in GISTs remains unclear. In this study, we applied SBC ceRNA microarrays to screen for tumour-specific circRNA profiles in GISTs and identified that a total of 5,770 circRNAs and 1,815 mRNAs were differentially expressed in GISTs. Three significantly differential circRNAs (circ_0069765, ci

The Role of Minimal Access Surgery in the Treatment of Spinal Metastatic Tumors.

Study designLiterature review.ObjectiveTo provide an overview of the recent advances in minimal access surgery (MAS) for spinal metastases.MethodsLiterature review.ResultsExperience gained from MAS in the trauma, degenerative and deformity settings has paved the road for MAS techniques for spinal cancer. Current MAS techniques for the treatment of spinal metastases include percutaneous instrumentation, mini-open approaches for decompression and tumor resection with or without tubular/expandable retractors and thoracoscopy/endoscopy. Cancer care requires a multidisciplinary effort and adherence

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro.

LncRNA LGALS8-AS1 Promotes Breast Cancer Metastasis Through miR-125b-5p/SOX12 Feedback Regulatory Network.

BackgroundMetastasis is a major factor weakening the long-term survival of breast cancer patients. Increasing evidence revealed that long non-coding RNAs (lncRNAs) were involved in the occurrence and development of breast cancer. In this study, we aimed to investigate the role of LGALS8-AS1 in the metastatic progression of breast cancer cells and its potential mechanisms.ResultsThe lncRNA LGALS8-AS1 was highly expressed in breast cancer and associated with poor survival. LGALS8-AS1 functioned as an oncogenic lncRNA that promoted the metastasis of breast cancer both in vitro and in vivo. It upr

Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.

Fasting mimicking diets (FMDs) are effective in the treatment of many solid tumors in mouse models, but their effect on hematologic malignancies is poorly understood, particularly in combination with standard therapies. Here we show that cycles of a 3-day FMD given to high-fat-diet-fed mice once a week increased the efficacy of vincristine to improve survival from BCR-ABL B acute lymphoblastic leukemia (ALL). In mice fed a standard diet, FMD cycles in combination with vincristine promoted cancer-free survival. RNA seq and protein assays revealed a vincristine-dependent decrease in the expressi

Протеомический анализ показывает, что потенциальные молекулы могут выступать посредником в кортикальной патологии и выявлять возможные биомаркеры в животной модели множественного склероза.

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой сложное нейродегенеративное заболевание, характеризующееся повторяющимися вспышками, обезвоживанием, повреждением аксона и последующей потерей функции. MS представляет широкий спектр клинических курсов, прогрессивные формы которых приводят к необратимой неврологической инвалидности. Кортикальные демиелионирующие повреждения имеют ключевое значение для патологии этих прогрессивных форм, и в последние десятилетия они приобретают решающее значение в силу их тесной связи с физической инвалидностью и когнитивным упадком. Несмотря на это, механ

Осколки периферальной крови, полученные в результате ТРНК, являются новыми неинвазивными биомаркерами для диагностики и прогнозируемой стратификации в множестве миеломы.

В последнее время в качестве критически важных регуляторов в области онкологической биологии появились небольшие РНК, полученные в результате передачи РНК; однако их профили экспрессии и клиническая значимость в нескольких миеломах (ММ) по-прежнему плохо определены. МЕТОДЫ: Секвенирование высокой производительности было проведено для всеобъемлющей характеристики профилей выражения ТСНК в периферийных моноядерных клетках крови (ПБМК) из 22 новые пациенты с диагнозом MM и 19 здоровый контроль. Общие целевые гены были предсказаны путем интеграции MiRanda и TookScan, и была создана сеть взаимодейс

CD200 является мощным новым фактором роста в Мультимиломе, зависящим от сигнала рецептора IGF1.

CD200 — это иммунный контрольно-пропускной пункт, безошибочно выраженный в 70% недавно диагностированных пациентов с множественной миеломой (ММ) и связанный с плохим исходом. Выражение CD200 клетками опухоли препятствует иммунной реакции через взаимодействие с CD200R и участвует в устойчивости к иммунной терапии. Однако его роль в опухоли остается слабой. В этом исследовании мы показываем, что клетки MM, перевыражающие CD200, представляют собой значительное пролиферативное преимущество в свободных культурных сыворотках, средних и клоногенных анализах. Преимущество роста клеток, опосредованное