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Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia.

BACKGROUND: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK-228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL. METHODS: We conducted a single-arm multi-center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI-9775). RESULTS: Sixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), w

Distinguishing Curable from Progressive Dementias for Defining Cancer Care Options.

The likelihood of a diagnosis of dementia increases with a person's age, as is also the case for many cancers, including melanoma and multiple myeloma, where the median age of diagnosis is above 60 years. However, patients diagnosed with dementia are less likely to be offered invasive curative therapies for cancer. Together with analysis of diet and medication history, advanced imaging methods and genetic profiling can now indicate more about syndromes causing the neurological symptoms. Cachexia, malnutrition, dehydration, alcohol consumption, and even loneliness can all accentuate or cause th

Агрессивная экстрамеуллярная миелома, представляющая собой маленькое препятствование.

De novo extramedullary multieloma (EMM) — редкая подмножество миеломы (MM), определяемая наличием клональных плазменных клеток (PC) за пределами костного мозга. Она связана с рефракторными заболеваниями и неблагоприятными последствиями. Даже в ЭММ плазменные цитомы внутри дуоденума, джеджунум и лилум редко встречаются при меньшем количестве 70 - случаи, о которых сообщается в литературе. Здесь мы представляем особо агрессивный случай ЭММ, который привел к тому, что маленький кишечник стал преградой для внутрисветовой плазмоцитомы во время лечения миэломы. Пациент прошел хирургическую пересечен

Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics.

Cancer is a group of diseases causing abnormal cell growth, altering the genome, and invading or spreading to other parts of the body. Among therapeutic peptide drugs, anticancer peptides (ACPs) have been considered to target and kill cancer cells because cancer cells have unique characteristics such as a high negative charge and abundance of microvilli in the cell membrane when compared to a normal cell. ACPs have several advantages, such as high specificity, cost-effectiveness, low immunogenicity, minimal toxicity, and high tolerance under normal physiological conditions. However, the develo

Gaucher Disease in Bone: From Pathophysiology to Practice.

Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years' of the literature, defining terms according to pathophysiological understanding and pointing out best practice and

T1-Dark Рим как знак новых и хронически активных множественных склерозов: Серийное исследование с частым 7T MRI.

ЦЕЛЬ И СПРАВОЧНАЯ ИНФОРМАЦИЯ: Хронические активные множественные повреждения склероза (MS) представляют собой особо разрушительную группу повреждений патологии. Однако их изображения коррелируют, в том числе с повреждениями парамагнитных ободов (ПБД), которые обнаруживаются на изображениях, взвешенных по степени чувствительности, и с трудом поддаются применению в клинической практике. В ходе этого исследования в продольном разрезе изучается распространенность и временная динамика нового маркера изображений, T1-dark В области количественного картирования уязвимости (QSM) были отмечены ободья и

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): Optimal Management.

Hyponatremia, defined as serum sodium concentration <135 mEq/l, is the most common electrolyte balance disorder in clinical practice. Many causes are listed, but syndrome of inappropriate antidiuretic hormone secretion (SIADH) is certainly the most relevant, mainly in oncological and hospitalized patients. In this review, the pathophysiological and clinical aspects are described in detail. Patients' extensive medical history and structured physical and biochemical tests are considered the milestones marking the way of the SIADH management as to provide early detection and proper correction. We

Predictive Modeling of Pharmacokinetic Drug-Drug and Herb-Drug Interactions in Oncology: Insights From PBPK Studies.

Physiologically based pharmacokinetic (PBPK) modeling is increasingly used to anticipate, quantify, and strategically manage drug-drug (DDI) and herb-drug (HDI) interactions that can alter the exposure of chemotherapy agents together with co-administered phytochemicals or nutraceuticals. To evaluate current knowledge, we performed a comprehensive Google Scholar search (2003-2024) and selected studies that employed PBPK platforms, reported quantitative validation, and focused on chemotherapy-related interactions. From these reports, key modeling parameters, validation metrics, and clinically re

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever.

BackgroundAutologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal an

Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature.

BackgroundOverdiagnosis of bronchopulmonary carcinoid tumors together with overtreatment can cause serious postoperative consequences for the patient. We report of a patient with a typical bronchopulmonary carcinoid tumor, which was initially misdiagnosed and treated as an adenocarcinoma of the lung. GnrH receptors and the associated Raf-1/MEK/ERK-1/2-pathway are potential targets for analogs in cancer treatment. We suspected a correlation between the lack of tumor growth, application of leuprolide and the Raf-1/MEK/ERK-1/2-pathway. Therefore, we examined GnrH receptor status in the examined s

Acute Disseminated Encephalomyelitis (ADEM): Current View into Etiopathogenesis and Clinical Features.

Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only partially understood. Clinically, the diagnosis of ADEM continues to pose significant challenges due to the absence of disease-specific biomarkers and its clinical and radiological overlap with other acquired demyelinating syndromes. This narrative re

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

Bone health in patients with cancer: a SEOM-SEIOMM consensus review of risk factors, assessment strategies, and management approaches.

Anticancer therapies frequently compromise skeletal health and increase fracture risk. This narrative review synthesizes information and provides guidance on assessment, prevention, and management of therapy-related bone loss in adults with cancer. Major contributors to bone loss in this population include aromatase inhibitors, androgen deprivation therapy, systemic glucocorticoids, chemotherapy, and selected targeted or immune agents. Recommended assessments include clinical evaluation, laboratory tests (calcium, vitamin D, and renal function), and bone mineral density by dual-energy X-ray ab

Combination therapy in combating cancer.

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival

Recent advances in management of COVID-19: A review.

The coronavirus disease 2019 (COVID-19) pandemic caused and is still causing significant mortality and economic consequences all over the globe. As of today, there are three U.S Food and Drug administration (FDA) approved vaccines, Pfizer-BioNTech, Moderna and Janssen COVID-19 vaccine. Also, the antiviral drug remdesivir and two combinations of monoclonal antibodies are authorized for Emergency use (EUA) in certain patients. Furthermore, baricitinib was approved in Japan (April 23, 2021). Despite available vaccines and EUA, pharmacological therapy for the prevention and treatment of COVID-19 i

Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following th

The role of social, economic, and medical marginalization in cancer clinical trial participation inequities: A systematic review.

Extant literature reveals how patients of marginalized social identities, socioeconomic status (SES), and medical experiences - especially patients of color and older adults - are underrepresented in cancer clinical trials (CCTs). Emerging evidence increasingly indicates CCT underrepresentation among patients of lower SES or rural origin, sexual and gender minorities, and patients with comorbid disability. This review applies an intersectional perspective to characterizing CCT representativeness across race and ethnicity, age, sexual and gender identity, SES, and disability. Four databases wer

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… therapy trials Proton therapy Race/ethnicity 5 Fayanju et al. 2019 Breast Any 809,843 total patients 17,214 accruals 792,719 non-accruals Compare cohort of current breast surgical oncology patients enrolled in CCTs and NCDB eligible patient non-accruals Surgical Race/ethnicity SES 5 Freudenburg et al … therapy trials | Proton therapy | Race/ethnicity | 5 Fayanju et al. | 2019 | Breast | Any | 809,843 total patients 17,214 accruals 792,719 non-accruals | Compare cohort of current breast surgical oncology patients enrolled in CCTs and NCDB eligible patient non-accruals | Surgical | Race/ethnicity SES …

Chronic Pain and Bone-Related Pathologies: A Narrative Review.

PurposePain related to bone may occur as a result of trauma, bone fracture, genetic disease, arthritis, benign or malignant primary bone tumors and bone cancer metastases. We discuss the pathophysiology of chronic bone-related pain, treatment options and therapeutic perspectives.MethodsUsing predefined terms, we searched PubMed, MEDLINE, and Google Scholar for meta-analyses, evidence-based reviews, and clinical practice guidelines. This narrative article reviews pathologies linked to chronic bone pain and discusses the preventive and therapeutic strategies for better bone pain management.Resul