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Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

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… lymphoma (2017) Bayer Duvelisib (Copiktra) PI3Kγ/δ CLL (2018) SLL (2018) Follicular lymphoma (2018) Verastem Alpelisib (Piqray) PI3Kα Breast cancer (2019) Novartis Temsirolimus (Torisel) mTOR RCC (2007) Pfizer Everolimus (Afinitor) mTOR RCC (2009) Pancreatic cancer (2011) Breast cancer (2012) Novartis Sirolimus … Copiktra) | PI3Kγ/δ | CLL (2018) SLL (2018) Follicular lymphoma (2018) | Verastem | Alpelisib (Piqray) | PI3Kα | Breast cancer (2019) | Novartis | Temsirolimus (Torisel) | mTOR | RCC (2007) | Pfizer | Everolimus (Afinitor) | mTOR | RCC (2009) Pancreatic cancer (2011) Breast cancer (2012) | Novartis | Sirolimus …

Резюме

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The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.

Mushrooms are valued for their nutritional qualities and have been used in traditional medicine since the Neolithic era. They exhibit various bioactivities, including antioxidant, hypocholesterolemic, immunomodulatory, and anticancer effects. The anticancer effects arise via direct action on tumor cells and indirect modulation of the immune system; the latter is the predominant mechanism. Numerous studies indicate that various mushroom species are potent immunostimulants because their cell wall polysaccharides and proteoglycans are recognized by intestinal immune cells. This enhances antitumor

Osteoimmunology in bone malignancies: a symphony with evil.

Bone marrow is pivotal for normal hematopoiesis and immune responses, yet it is often compromised by malignancies. The bone microenvironment (BME), composed of bone and immune cells, maintains skeletal integrity and blood production. The emergence of primary or metastatic tumors in the skeletal system results in severe complications and contributes significantly to cancer-related mortality. These tumors set off a series of interactions among cancer, bone, and immune cells, and disrupt the BME locally or distantly. However, the drivers, participants, and underlying molecules of these interactio

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

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… cancer 2005 Marqibo Acrotech Liposome Vincristine sulfate Acute lymphoblastic leukemia 2012 Onivyde Ipsen Liposome Irinotecan hydrochloride Metastatic pancreatic cancer 2015 Vyxeos Celator Pharms Liposome Cytarabine Daunorubicin Acute myeloid leukemia 2017 Fyarro Aadi Sub Albumin-bound nanoparticles Sirolimus … Liposome | Vincristine sulfate | Acute lymphoblastic leukemia | 2012 Onivyde | Ipsen | Liposome | Irinotecan hydrochloride | Metastatic pancreatic cancer | 2015 Vyxeos | Celator Pharms | Liposome | Cytarabine Daunorubicin | Acute myeloid leukemia | 2017 Fyarro | Aadi Sub | Albumin-bound nanoparticles | Sirolimus …

Selected Abstracts from the 12th Annual Meeting of the Clinical Immunology Society: 2021 Virtual Annual Meeting: Immune Deficiency and Dysregulation North American Conference.

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Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients.

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlappi

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… pathway. 91 Also, inhibition of phosphatidylinositol 3-kinase-dependent NO production has been proposed, but the exact mechanisms underlying BTK inhibitor-induced hypertension have not been characterized. 92 mTOR Inhibitors Inhibitors of mTOR (mammalian target of rapamycin), including everolimus and sirolimus …

Current and Emerging Therapies for Targeting the ERK1/2 & PI3K Pathways in Cancer.

The ERK1/2 and PI3K signaling pathways play important roles in cellular proliferation, survival, differentiation, and metabolism. In cancer, these pathways are frequently dysregulated and overactivated, resulting in poor patient prognosis and resistance to treatment. These pathways are activated by receptor tyrosine kinases and send downstream signals to effectors such as RAS, RAF, MEK, AKT, and mTOR. In this review, we highlight the key components of the ERK1/2 and PI3K pathways, the roles they play in tumor progression, and the development of inhibitors and combination therapies designed to

Long-Term Health Effects of Curative Therapies on Heart, Lungs, and Kidneys for Individuals with Sickle Cell Disease Compared to Those with Hematologic Malignancies.

The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and minimize intermediate and long-term adverse outcomes so that individuals can live an average life span with a high quality of life. While greater than 2000 individuals with SCD have been treated with curative therapy, systematic studies have not been performed to evaluate the long-term health effects of hematopoietic stem cell transplant (HSCT) in this population. Individuals with SCD suffer progressive heart, lung, and kidney disease prior to curative therapy. In adults, these sequalae are associ

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… More frequent testing may be required for patients on sirolimus. Consider not starting treatment unless documentation that albuminuria is persistent upon repeat testing. 11. Measure blood pressure yearly. 12. Renal consultation is recommended for patients with renal dysfunction. …

Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism.

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long

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… To date, there are various types of non-ablative approaches based on a low-intensity TBI in combination with fluradabine or cloforabine followed by treatment with mycophenolate mofetil and a calcineurin inhibitor ± sirolimus, such as in the cohort studies published by Cooper et al. ( 34 ); or such as …

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

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… Sirolimus and mTOR inhibitors: a review of side effects and specific management in solid organ transplantation. Drug Safety 42 (7), 813–825. 10.1007/s40264-019-00810-9 Noren Hooten N., Martin-Montalvo A., Dluzen D. F., Zhang Y., Bernier M., Zonderman A. B., et al. (2016). …

The 44th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Poster Sessions

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Secondary antibody deficiencies: what's around the corner?

Secondary antibody deficiencies (SADs) are characterized by impaired humoral immunity, which can cause recurrent and severe infections. Several factors may contribute to SAD development, making it difficult to establish a clear etiological classification. This heterogeneity also leads to clinical variability, further complicating patient management and treatment strategies. Various diagnostic and therapeutic algorithms are often adapted from those used in primary antibody deficiencies, potentially resulting in under- or over-treatment. Key points include the decision to initiate Immunoglobulin

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… Depending on the mode of action, these drugs may be classified as antimetabolite agents (methotrexate, mofetil mycophenolate, azathioprine), calcineurin inhibitors (Cyclosporin A, Tacrolimus), and mTor Inhibitors (sirolimus, everolimus) ( 112 ). …

Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications.

Background: Since the 1990s, transplantations of hematopoietic and mesenchymal stem cells (HSCT and MSCT) and dendritic cell (DCT) have been investigated for the treatment of neurological autoimmune disorders (NADs). With the growing number of transplanted patients, awareness of neuroimmunolgical complications has increased. Therefore, an overview of SCT for the most common NADs and reports of secondary immunity after SCT is provided. Methods: For this narrative review, a literature search of the PubMed database was performed. A total of 86 articles reporting on different SCTs in NADs and 61 a

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… Treatment with different immunosuppressive therapies (corticosteroids, azathioprine, cyclosporine, MMF, IVIG, plasmapheresis, sirolimus, tacrolimus, rituximab, vincristine, and cyclophosphamide) resulted in complete or partial recovery or control of disease in almost all patients [ 32 , 136 , 137 , 138 …

Primed for global coronavirus pandemic: Emerging research and clinical outcome.

The global effort to combat and contain the coronavirus disease 2019 (COVID-19) caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now proceeding on a war footing. The world was slow to react to the developing crisis, but once the contours of the impending calamity became evident, the different state and non-state actors have raced to put their act together. The COVID-19 pandemic has blatantly exposed the shortcomings of our healthcare system and the limitations of medical science, despite considerable advances in recent years. To effectively tack

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… 57 | Tofacitinib ( 61 ) | Università Politecnica Delle Marche (UNIVPM), Italy | Phase-II, NCT04332042 ( ClinicalTrials.gov ) | Janus kinase (JAK) inhibitor 58 | Spironolactone ( 62 ) | Istanbul University-Cerrahpasa, Turkey | Phase-IV, NCT04345887 ( ClinicalTrials.gov ) | Aldosterone antagonist 59 | Sirolimus …

Current Diagnosis and Management of Primary Chylomicronemia.

Primary chylomicronemia (PCM) is a rare and intractable disease characterized by marked accumulation of chylomicrons in plasma. The levels of plasma triglycerides (TGs) typically range from 1,000 - 15,000 mg/dL or higher.PCM is caused by defects in the lipoprotein lipase (LPL) pathway due to genetic mutations, autoantibodies, or unidentified causes. The monogenic type is typically inherited as an autosomal recessive trait with loss-of-function mutations in LPL pathway genes (LPL, LMF1, GPIHBP1, APOC2, and APOA5). Secondary/environmental factors (diabetes, alcohol intake, pregnancy, etc.) often

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… • Medications : Glucocorticoids, oral estrogens (contraceptives, postmenopausal replacement therapies), clomiphene, tamoxifen, exogenous testosterone; retinoids such as isotretinoin, bexarotene; immunosuppressants and anticancer drugs such as sirolimus, cyclosporine A, tacrolimus, capecitabine, cyclophosphamide …

The 48th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Poster Session (P001 - P578).

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The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.

Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME-a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune c

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… Rapamycin The mTOR inhibitor rapamycin (sirolimus) and its analogs (rapalogs, e.g., everolimus, temsirolimus) have been shown to possess significant anti-angiogenic, immunosuppressive, antifungal, and anti-tumor properties. …

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

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… The two drugs currently used in the field of oncology, Temsirolimus (Torisel®) and Everolimus (Afinitor®) were derived from rapamycin (Sirolimus) and are still used in different tumor forms, such as renal cell carcinoma, mantle cell lymphoma, breast cancer and neuroendocrine pancreatic carcinoma (Fasolo …

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment str

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… Temsirolimus is a derivative and prodrug of the widely used immunosuppressant sirolimus, also known as rapamycin (see Section 5 for more details). Rapamycin and its derivatives act by inhibiting mTOR [ 186 , 187 ]. …