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Гибридные нанопчасти на основе гиалюронной кислоты в качестве перспективных перевозчиков Интранасальной администрации диметилФумарата.

ПППОСА: Диметилфумарат (ДМФ) - пероральная терапия с релапсирующим множественным склерозом, быстро метаболизируется в монометилфумарат. Оральное управление DMF вызывает желудочно-кишечный дискомфорт, вызывая вынос лечения. Цель настоящего исследования заключается в разработке новаторской формулировки для управления носовым слоем ДМФ. Гибридные наночастицы (LPN) липидового полимера были разработаны для повышения устойчивости DMF, ограничения побочных эффектов желудочно-кишечного кишечника и увеличения биодоступности головного мозга за счет нацеливания нос на мозг.МЕТОДЫ: С помощью методов магни

Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple myeloma.

Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification of chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in 30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine RNA editing has recently emerged as a driver of cancer progression, genomic amplification combined with inflammatory cytokine activation of ADAR1 could stimulate MM progression and therapeutic resistance. Here, we report that high ADAR1 RNA expression correlates with reduced patient survival

Logic programming reveals alteration of key transcription factors in multiple myeloma.

Innovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected r

Mapping oncogenic protein interactions for precision medicine.

Normal protein-protein interactions (normPPIs) occur with high fidelity to regulate almost every physiological process. In cancer, this highly organised and precisely regulated network is disrupted, hijacked or reprogrammed resulting in oncogenic protein-protein interactions (oncoPPIs). OncoPPIs, which can result from genomic alterations, are a hallmark of many types of cancers. Recent technological advances in the field of mass spectrometry (MS)-based interactomics, structural biology and drug discovery have prompted scientists to identify and characterise oncoPPIs. Disruption of oncoPPI inte

Increased Indoleamine 2, 3-Dioxygenase expression modulates Th1/Th17/Th22 and Treg pathway in humans with Helicobacter Pylori-Infected gastric mucosa.

Introduction and purposeIndoleamine 2, 3- dioxygenase (IDO) plays an importantrole in immunosuppressive pathway, as inhibits responsesof T cells and promotes immune tolerance. Host responsetoHelicobacter pylori (H. pylori) is involved in the infection persistenceand it is also associatedwith different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulato

RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes to achieve posttranscriptional gene regulation. RNAi has proven to be an adaptable and powerful therapeutic strategy where advancements in chemistry and pharmaceutics continue to bring RNAi-based drugs into the clinic. With four siRNA medications already approved by the US Food and Drug Administration (FDA), several RNAi-based thera

Определение биологических границ монотерапии Daratumumumab: долгосрочные исследования из исследования CENTAURUS по множественной миеломе, вызывающей повышенный риск.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Preventive Healthcare and Management for Acute Lymphoblastic Leukaemia in Adults: Case Report and Literature Review.

Acute lymphoblastic leukaemia (ALL) is diagnosed by the presence of at least 20% lymphoblasts in the bone marrow. ALL may be aggressive and include the lymph nodes, liver, spleen, central nervous system (CNS), and other organs. Without early recognition and timely treatment, ALL will progress quickly and may have poor prognosis in clinical scenarios. ALL is a rare type of leukaemia in adults but is the most common type in children. Precipitating factors such as environmental radiation or chemical exposure, viral infection, and genetic factors can be associated with ALL. We report a rare case o

Совпадение в полном тексте источника
… For patients with ALL with unsuccessful cytogenetic analysis or normal karyotypes under conventional cytogenetic analysis, it is possible to determine aberrations with comparative genomic hybridization [ 28 ]. Several methods have been developed to understand the leukaemogenesis of ALL. …

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major challenge to targeted therapy for non-small cell lung cancer (NSCLC). We investigated whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse EGFR-TKI resistance in human lung cancer cells and explored the underlying mechanisms. We found that PD 0332991 potentiated gefitinib-induced growth inhibition in both EGFR-TKI-sensitive (PC-9) and EGFR-TKI-resistant (PC-9/AB2) cells by down-regulating proliferation and inducing apoptosis and G0/G1 cell cycle arrest. Tumor xenogra

Эпигенетические достижения в педиатрическом многоразовом склерозе: ДНК-метилирование примечательно участие Эпштейна-Барра заражённых вирусом и принимающих иммунных сетей.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛИ: Педиатрический множественный склероз (PedMS) предоставляет уникальную возможность для изучения патогенеза MS с учетом короткого интервала между воздействием на окружающую среду и возникновением заболеваний. Цель этого исследования состояла в том, чтобы выявить различные метилированные регионы (ДМР), которые способствуют взаимодействию между экологическими факторами и геномными факторами на ранних этапах заболевания. В этом многоцентровом исследовании мы проанализировали периферическую ДНК крови. 175 Итальянские предметы122 Пациенты педиатрии, 53 - здоровый контрол

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

Текущая стратификация и установка множественных миелом и связанные с этим нарушения клональной плазменной клетки.

Клональные расстройства плазменных клеток охватывают целый спектр таких заболеваний, как множественная миелома (ММ), моноклонная гаммопатия неопределённого значения (МГУС), хмельная миелома (МММ), макроглобулиномия Уолденстрёма (ВМ) и амилоидоз иммуноглобулиновой цепи. В MGS, SMM и MM риск развития сильно варьируется и зависит от сложного взаимодействия нагрузки опухоли, цитогенетических аномалий, микроокружающей среды костного мозга и факторов хостинга. Уолденстрёмская макроглобулинемия, хотя она обычно и является бестактной, представляет собой свой собственный спектр молекулярных аномалий и

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

Множественные модели миэломы и витро человека для моделирования заболеваний и скрининга на лечение.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся неконтролируемым расширением злокачественных плазменных клеток в микроокружающей среде костного мозга. В то время как культуры подвески клеточных линий MM и мусриновых моделей были краеугольным камнем исследований MM патогенез, эти традиционные системы не могут воспроизвести критические аспекты микроопухоли человека. В частности, нынешние модели неадекватно учитывают ключевые биологические вопросы, включая механизмы приобретения лекарственного сопротивления, стратегии уклонения от иммунитета и роль клеточного перекрестка в

E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.

Therapy resistance in gastrointestinal tumors remains a critical challenge in clinical oncology, severely compromising therapeutic efficacy and long-term patient survival. E3 ubiquitin ligases, as core enzymes involved in the protein ubiquitination process, have been demonstrated to play indispensable roles in regulating key biological processes in tumor cells, including DNA damage repair, cell cycle progression, apoptosis, cancer stem cell maintenance, and immune evasion. Additionally, E3 ligases are key regulators of resistance to multiple anticancer strategies, such as chemotherapy, radioth

Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein-Barr Virus Infection.

Epstein-Barr virus (EBV), a type 4 γ herpes virus, is recognized as a causative agent in nasopharyngeal carcinoma (NPC). Incidence of EBV-positive NPC have grown in recent decades along with worse outcomes compared with their EBV-negative counterparts. Latent membrane protein 1 (LMP1), encoded by EBV, induces NPC progression. The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases (RTK), is a driver of tumorigenesis, including for NPC. Little data exist on the relationship between EGFR and EBV-induced NPC. In our initial review, we found that LMP1

Expert Perspective: Hematologic Malignancies and Vasculitis.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Functional Investigation of IGF1R Mutations in Multiple Myeloma.

High expression of the receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) and RTK mutations are associated with high-risk/worse prognosis in multiple myeloma (MM). Combining the pIGF1R/pINSR inhibitor linsitinib with the proteasome inhibitor (PI) bortezomib seemed promising in a clinical trial, but IGF1R expression was not associated with therapy response. Because the oncogenic impact of IGF1R mutations is so far unknown, we investigated the functional impact of IGF1R mutations on survival signaling, viability/proliferation and survival response to therapy. We transfe

The novel cancer-testis antigen A-kinase anchor protein 4 (AKAP4) is a potential target for immunotherapy of ovarian serous carcinoma.

Ovarian cancer is one of the neoplasms affecting the reproductive tract associated with high mortality rate because of limited therapeutic options and an elevated incidence of chemoresistance and recurrence. In this context, immunotherapy may constitute a promising approach to improve survival rates and clinical outcome, raising the need for specific target antigens. Cancer-testis antigens (CTAs) are considered promising candidates in this sense because they are aberrant expressed by various malignancies but not by non-transformed tissue, with the exception of testes. Here, we examined the exp

Plasmablastic Lymphoma: Case Report of Prolonged Survival of an Advanced Human Immunodeficiency Patient and Literature Review.

Clinical Practice Points. Plasmablastic lymphoma (PBL) is a rare and highly aggressive variant of diffuse large B cell lymphoma with median survival of advanced stage patients varying between 6 and 15 months in previous reports. We report here a human immunodeficiency virus-infected patient surviving over 12 years following treatment for advanced PBL with EPOCH chemotherapy and intrathecal therapy. This case highlights the potential for improved survival in PBL with intensive chemotherapy. Further, literature review suggests promising prospects utilizing novel targeted therapies to increase th

Совпадение в полном тексте источника
… Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma. Journal of Hematology and Oncology. 2009;2, article 47 doi: 10.1186/1756-8722-2-47. 3. …