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Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.

Antimicrobial resistance is an important issue for global health; in immunocompromised patients, such as solid organ and hematological transplant recipients, it poses an even bigger threat. Colonization by multidrug-resistant (MDR) bacteria was acknowledged as a strong risk factor to subsequent infections, especially in individuals with a compromised immune system. A growing pile of studies has linked the imbalance caused by the dominance of certain taxa populating the gut, also known as intestinal microbiota dysbiosis, to an increased risk of MDR bacteria colonization. Several attempts were p

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… Her immunosuppressant regime consisted of cyclosporine, sirolimus, and prednisone. FMT was delivered via a nasogastric tube, without prior preparation. Loss of VRE fecal dominance was documented at weeks 1 and 3 and at seven months after the procedure. …

Nanomedicine: Principles, Properties, and Regulatory Issues.

Several scientific areas have benefited significantly from the introduction of nanotechnology and the respective evolution. This is especially noteworthy in the development of new drug substances and products. This review focuses on the introduction of nanomedicines in the pharmaceutical market, and all the controversy associated to basic concepts related to these nanosystems, and the numerous methodologies applied for enhanced knowledge. Due to the properties conferred by the nanoscale, the challenges for nanotechnology implementation, specifically in the pharmaceutical development of new dru

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… Prolonged release suspension for injection | Schizophrenia | Olanzapine pamoate Zypadhera® | Powder and solvent for prolonged release suspension for injection | Schizophrenia | Aprepitant Emend® | Capsule | Nausea and vomiting | Fenofibrate Tricor® Lipanthyl® Lipidil® | Tablet | Hiperlipidemia | Sirolimus …

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention.

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstre

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob

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… [ 275 ] Drugs targeting GSH/TRX system PX-12 | Inhibitor of thioredoxin-1 (TRX-1) | Advanced or metastatic solid tumors (single agent) | Phase I, completed | NCT00736372 [ 276 ] Auranofin | Approved as antirheum- atic drug, with activity tar- geting TrxR | Recurrent ovarian cancer (combination with sirolimus … )/advanced or recurrent SCLC or NSCLC (combination with sirolimus) | Phase I/II, active | NCT03456700 NCT01737502 Relapsed or refractory CLL (single agent)/recurrent glioblastoma (9 repurposed drugs combined with temozolomide) | Phase I/II, completed | NCT01419691 NCT02770378 [ 277 ] Ethaselen | Selective …

Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.

Companion diagnostics (CDx) plays a pivotal role in precision medicine by enabling personalized treatment plans based on individual biomarker profiles. This approach can enhance therapeutic efficacy in selected indications and may reduce healthcare expenditures. Particularly in oncology, precision targeted therapies targeting pathways such as EGFR, HER2, and programmed death-1/programmed death-ligand 1 have established robust models for biomarker-driven treatment. However, rapid advancements in diagnostic technologies, expanding application scopes, and increasingly complex mechanisms of biomar

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… . | [ 226 ] P‐tau217 | Alzheimer's disease | — | Electrochemiluminescence | Accurately predicts amyloid PET positivity in cognitively unimpaired individuals | [ 227 ] GDF‐15 | Epithelioid hemangioendothelioma | Sirolimus | CT | GDF‐15 predicts epithelioid hemangioendothelioma aggressiveness. | [ 228 …

Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.

The thioredoxin (Trx) system, an integral component of cellular redox regulation, preserves protein dithiol-disulfide equilibrium through its conserved Cys-Gly-Pro-Cys active site and is involved in key cellular functions, including cell proliferation, apoptosis, and signal transduction. In cancer biology, the thioredoxin system plays dual roles: overexpression can suppress oxidative stress and promote tumor growth, whereas dysfunction can trigger programmed cell death (PCD). However, a critical area for future research is to delineate how Trx modulates the intricate networks of PCD, and to id

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… NCT02063698 Pain COMPLETED 2014.02-2016.11 • Auranofin in Treating Patients With Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer NCT01747798 Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer COMPLETED 2012.11-2015.04 • Sirolimus … COMPLETED | 2014.02-2016.11 • Auranofin in Treating Patients With Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | NCT01747798 | Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer | COMPLETED | 2012.11-2015.04 • Sirolimus …

Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes sha

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… At doses and blood levels achievable in humans, mTORC1 inhibiting rapalogs (sirolimus and everolimus) ameliorated PKD in cy/+ Han:SPRD rats, a model affecting proximal tubules, but not in PCK rats, a model affecting the distal nephron and collecting duct ( Shillingford et al., 2006 ). …

Total Body Irradiation in Haematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia: Review of the Literature and Future Directions.

Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy

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… . | ( 175 , 176 , 178 ) Higher SOS incidences may be seen with the addition of other drugs such as sirolimus. | ( 179 ) In preclinical studies and clinical studies in patients with a haematologic malignancy, busulfan and cyclophosphamide conditioning showed more frequent SOS occurrence than TBI conditioning …

Kidney Disease and Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with hematologic malignancies and certain solid tumors and nonmalignant hematologic conditions. Both AKI and CKD occur commonly after HSCT and are associated with significant morbidity and mortality. AKI and CKD in this setting may result from direct effects of the transplant or be caused by pretransplant bone marrow conditioning regimens and/or nephrotoxic agents administered in the post-transplant period. In this article, we review the epidemiology, risk factors, etiologies, pathophysiology, diagnos

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… regimen and donor source should be tailored to individual disease status/comorbidities. 17 , 36 RIC may be considered in high-risk patients. 17 A recent study by Abramson et al. demonstrated lower AKI incidence after T-cell–depleted HSCT as compared with unmodified transplant (tacrolimus-, tacrolimus-/sirolimus …

[Retracted] miR‑23a suppresses pancreatic cancer cell progression by inhibiting PLK‑1 expression.

BACKGROUND: One presentation of Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by picky eating, i.e., selective eating based on the sensory properties of food. The present study has two aims. The first is to describe distress and impairment in individuals with ARFID secondary to picky eating. The second is to determine whether eating behaviors hypothesized to be specific to picky eating can differentiate picky eaters with and without ARFID from typical eaters (e.g., individuals not reporting picky or disordered eating) and individuals who strongly endorse attitudes associat

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… Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J. Neuro. Oncol. 2010;96:219–230. doi: 10.1007/s11060-009-9950-0. 77. Galanis E, et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J. …

Understanding Rare Anemias: Emerging Frontiers for Diagnosis and Treatment.

Background-This review provides a comprehensive overview of rare anemias, emphasizing their hereditary and acquired causes, diagnostic advancements, and evolving treatment strategies. It outlines the significance of rare anemias within public health, historical challenges in recognition and treatment, and the role of European initiatives like ENERCA and EuroBloodNet in advancing care. Content-This document discusses diagnostic technologies like next-generation sequencing and the impact of artificial intelligence, alongside the promising avenues of gene therapy, targeted drug treatments, and st

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… Recent studies have emphasized the potential benefits of incorporating eltrombopag and sirolimus, particularly in refractory cases or those intolerant to cyclosporine A. Eltrombopag, either as monotherapy or in combination with other therapies, has shown promising improvements in patient outcomes. …

Chemotherapy-Associated Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia and thrombocytopenia with end-organ dysfunction. Although the advent of plasma exchange, immunosuppression, and complement inhibition has improved morbidity and mortality for primary TMAs, the management of secondary TMAs, particularly drug-induced TMA, remains less clear. TMA related to cancer drugs disrupts the antineoplastic treatment course, increasing the risk of cancer progression. Chemotherapeutic agents such as mitomycin-C, gemcitabine, and platinum-based drugs as well as targeted therapies such as anti

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… 62 Late-onset TMA associated with MMACHC mutation-induced cobalamin-C deficiency has also been reported. 63 Hematopoietic stem cell transplant–associated TMA (TA-TMA): In patients with recent HSCT, TA-TMA may occur secondary to high-intensity conditioning regimen, radiation, calcineurin inhibitors, sirolimus …

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

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… Myelodysplastic syndrome (MDS) •Non-Hodgkin lymphoma (NHL) | •Drug: Anti-thymocyte globulin (rabbit) •Drug: Blinatumomab •Drug: Cyclophosphamide •Drug: Fludarabine •Drug: G-CSF •Drug: Melphalan •Drug: Mesna •Drug: Rituximab•Drug: Tacrolimus •Drug: Thiotepa •Biological: HPC, A Infusion •Device: CliniMACS •Drug: Sirolimus …

Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review.

The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Although the advancement of modern immunotherapeutic approaches can increase the survival rate of cancer patients, new modalities are essential for improved therapeutic outcomes. Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration. It has been thought that EVs can reduce the risks and side eff

Esid 2014 oral presentations.

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Small molecule inhibitors targeting the cancers.

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatme

Полнотрансформатная ретиноидальная кислота в гематологическое расстройство: не только острая промиелоцитическая лейкемия.

Всетранс-ретиноиновая кислота (ATRA) играет определенную роль в развитии тканей, нейронной функции, воспроизводстве, зрение, росте и дифференциации клеток, иммунитете от опухоли и апоптозе. АТРА может действовать, вызывая автофагическую сигнализацию, ангиогенез, клеточную дифференциацию, апоптоз и иммунную функцию. В крови ATRA впервые с большим успехом использовалась в острой промиелоцитической лейкемии (APL), где ATRA дифференцировала клетки лейкемии на зрелые гранулоциты. АТРА может играть определенную роль не только в ППН, но и в других гематоологических заболеваниях, таких, как иммунная т

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… Anderson Cancer Center | Phase 2 | APL | 151 | NCT01409161 Sirolimus, ATRA | Peking Union Medical College Hospital | Phase 2 | Auto-Immune Anemia | 50 | NCT04324411 Phase 3 TAS1440, ATRA | Astex Pharmaceuticals, Inc | Phase 1 | R/R AML | 80 | NCT04282668 Chidamide, venetoclax | Shanghai Jiao Tong University …

" Нанотехнология " : новые стратегии для многократной терапии миеломы.

Достижения в области нанотехнологии открыли новые возможности для диагностики и лечения множественной миеломы (ММ), гематологической злокачественности, характеризующейся клональным распространением плазменных клеток в костном мозге. В этом обзоре раскрывается потенциал нанотехнологии для революции миэломы с уделением особого внимания системам доставки наркотиков наночастиц, методам наномасштабной съемки и наноиммунотерапии. Системы доставки наркотиков, основанные на нанопартии, обеспечивают повышенную целенаправленность наркотиков, снижение системной токсичности и повышение терапевтической эфф

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… For example, Rapamune, an oral nanoparticle formulation of sirolimus, has greatly improved the ease of administration compared to intravenous forms [ 63 ]. …

Нацеливание moTOR сигнализирующих путей в нескольких миеломах: биология и последствия для терапии.

Множественная миелома (ММ), рак неизлечимо дифференцированных плазменных клеток, является вторым по распространенности гематологической злокачественности и неизлечимо из-за неизбежного развития лекарственной устойчивости. Интенсивный синтез белка является отличительной чертой клеток MM, поддерживающей массовое производство клональных иммуноглобулинов или свободных световых цепей. Млекопитающая цель рэпамицин (mTR) киназы ценится как главный регулятор жизненно важных клеточных процессов, включая регулирование метаболизма и синтеза белка, и может быть найдена в two Мультипротеиновые комплексы, M

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… NVP-BEZ235 induces synergistic cell death when combine with BZ, dexamethasone and doxorubicin | [ 152 ] The mTORC1 inhibitor rapamycin (sirolimus) and the rapamycin analogue (rapalog) CCI-779 were the first to be examined in MM, and were shown to have anti-tumor effects in cells containing PTEN mutations …

Cardiac Interventions in Patients With Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit con

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… In the recent MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation with an Abbreviated versus Standard DAPT Regimen) trial, patients with acute or chronic coronary syndrome who had had successful PCI using a biodegradable sirolimus-eluting stent …