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Targeting PI3K/Akt/mTOR Signaling in Cancer.

The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are two pathways crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions (e.g., cancer). Indeed, they are so interconnected that, in a certain sense, they could be regarded as a single, unique pathway. In this paper, after a general overview of the biological significance and the main components of these pathways, we address the present status of the development of specific PI3K, Akt, and mTOR inhibitors, from already registered medici

Schwann Cell Activity in the Multiple Sclerosis Microenvironment.

Schwann cell (SC)-based therapy is currently being debated as an approach to promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). The main limitation of SC transplantation in MS patients is the short-term functional activity of SCs in the CNS environment. The goal of this study was to determine phenotypic, functional, and signaling changes in human SCs treated with CSF samples from MS patients in vitro, and to characterize the molecular mechanisms underlying SC injury response in the model MS mic

A novel hollow iron nanoparticle system loading PEG-Fe3O4 with C5a receptor antagonist for breast cancer treatment.

Breast cancer is the most diagnosed malignancy and major cause of cancer death among women population in the worldwide. Ferroptosis is a recently discovered iron-dependent regulated cell death involved in tumor progression and therapeutic response. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells like developing iron nanoparticles as a therapeutic agent. However, resistance to ferroptosis is a vital distinctive hallmark of cancer. Therefore, further investigation of the mechanism of ferroptosis resistance to enhance its tumor sensit

BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medica

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… Prothrombin time and international normalized ratio should be monitored in imatinib- and nilotinib-treated patients taking warfarin, while dasatinib-treated patients taking warfarin, heparin, enoxaparin, nadroparin, and dalteparin may have an elevated risk of bleeding. 46 Also, because there is an increased … Drug–drug interactions between frontline BCR-ABL1 TKIs and anticoagulants. 46 NR: no reported or expected interaction. a With increased anticoagulation monitor prothrombin time with international normalized ratio. b Increased risk of bleeding is due to thrombocytopenic effect that is generally caused …

Механизм поглощения и токсичности антителного препарата BCMA в сочетании с полезной нагрузкой MMAF неантигенными функционирующими элементами.

Belantamab mafodotin, антитело-наркомания (ADC), продемонстрировал высокую эффективность в множестве миеломы. Он состоит из гуманизированного антиклектового антигена (BCMA) IgG1 моноклонального антитела, смешанного с монометил-ауристатином F (MMAF) с помощью манимидокапроилового связующего устройства. С помощью неизвестных механизмов поступили сообщения о связанных с окультизмом неблагоприятных явлениях, в частности о роговицах, в которых содержится АКЦ, в том числе белантамб мафодотин. В ходе этого исследования изучался механизм поглощения и цитотоксичности белантамбом мафодотином, содержащим

Presentation of multiple myeloma mimicking bone metastasis from colon adenocarcinoma: A case report and literature review.

We herein present the case report of a 83-year-old female patient who had undergone right colon resection for adenocarcinoma 2 years earlier, and developed osteolytic lesions of the right femur 6 months ago. A roentgenogram of the right thigh, technetium-99m phosphate bone scintigraphy and combined 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging were performed, and the results revealed multiple osteolytic lesions in the humerus bilaterally, the right scapula and the right femur. The lesions were suspected to be colon cancer metastases. To improve the quali

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidiscip

Long-Term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography a

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the d

Глубокие вены: многообещающий нейроимационный маркер для нейродегенерации в множестве склерозов.

Множественный склероз (MS) — хроническое аутоиммунное заболевание центральной нервной системы (КНС). Недавние исследования показали, что различные формы сосудистых аномалий могут быть связаны с патогенезом MS. Снимки, взвешенные на сушке, могут непосредственно изображать внутричерепные яйцеклетки. Цель этого исследования заключалась в изучении связи между глубокими медуллярными венами (ДМВ) и степенью нейродегенерации у пациентов с MS. МЕТОДЫ: В рамках этого перспективного перекрестного исследования были приняты на работу 34 пациента с синдромом MS и 30 сравниваемых по возрасту здоровых (HC).

MicroRNA-21-5p profile in the alveolar bone following tooth extraction in medication-related osteonecrosis of the jaw rat model.

OBJECTIVE: This study aimed to compare microRNA-21-5p expressions at the extraction wound in the maxillary bones of rats with medication-related osteonecrosis of the jaw (MRONJ) and normal rats at different time points. MATERIALS AND METHODS: In total, 18 female, 8-week-old Sprague-Dawley rats were randomly assigned to the experimental group (n = 9) and the control group (n = 9). To establish MRONJ in the right maxillary first molar area in the experimental group, zoledronate (66 µg/kg) and dexamethasone (5 mg/kg) were administered intraperitoneally every other day for 2 weeks before tooth ex

Cardiometabolic health in people with HIV: expert consensus review.

ObjectivesTo develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts.MethodsA targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in

Advances in Diet and Physical Activity in Breast Cancer Prevention and Treatment.

There is currently a growing interest in diets and physical activity patterns that may be beneficial in preventing and treating breast cancer (BC). Mounting evidence indicates that indeed, the so-called Mediterranean diet (MedDiet) and regular physical activity likely both help reduce the risk of developing BC. For those who have already received a BC diagnosis, these interventions may decrease the risk of tumor recurrence after treatment and improve quality of life. Studies also show the potential of other dietary interventions, including fasting or modified fasting, calorie restriction, keto

Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.

Alternative splicing (AS) is the central mechanism of transcriptional regulation and generates diverse splice variants that influence protein structure, function, and intracellular activity. AS plays critical roles in tissue differentiation, organ development, and disease progression. This review focuses on the pivotal roles of AS in bone biology, highlighting its regulatory effects on osteoblasts, osteoclasts, chondrocytes, bone matrix remodeling, and bone remodeling, as well as the involvement of AS-related RNA-binding proteins in these processes. We also emphasize bone-specific AS events an

Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature.

Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyl

Management of relapsed/refractory AL amyloidosis.

AbstractFrontline therapy for systemic amyloid light chain (AL) amyloidosis has evolved significantly with the approval of daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone, which has significantly improved rates of both hematologic and organ responses. Despite these advances, many patients eventually relapse, and there remains no established standard salvage regimen or optimal timing. In this review, we examine optimal timing of salvage regimens and currently available therapeutic options after daratumumab failure, including next-generation proteosome inhibitors

Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy: A multicenter Intergroupe Francophone du Myélome study.

Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familia

Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 12

Pertussis in Individuals with Co-morbidities: A Systematic Review.

Pertussis is a highly contagious disease of the respiratory tract caused by Bordetella pertussis. Although the burden of pertussis is highest in children, available data suggests that pertussis in the elderly and those with underlying chronic conditions or illnesses can result in significant morbidity, mortality and costs. We undertook a comprehensive review to assess the association between pertussis and chronic conditions/illnesses. A search was undertaken on 17 June 2019 across EMBASE, Medline and BIOSIS. Citations were limited to those in English, in humans and published since 1 January 19

Prognostic pan-cancer and single-cancer models: A large-scale analysis using a real-world clinico-genomic database.

Prognostic models in oncology have a profound impact on personalized cancer care and patient profiling, but tend to be heterogeneously developed and implemented in narrow patient cohorts. Here, we develop and benchmark multiple machine learning models to predict survival in pan-cancer and 16 single-cancer settings using a de-identified clinico-genomic database of 28,079 US patients with cancer. We identify key predictors of cancer prognosis, including 15 shared across seven or more cancer types, revealing strong consistency in cancer prognostic factors. We demonstrate that pan-cancer models ge