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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

Advanced Practice Perspectives on Preventing and Managing Tumor Lysis Syndrome and Neutropenia in Chronic Lymphocytic Leukemia.

Tumor lysis syndrome (TLS) and neutropenia are significant toxicities in the treatment of chronic lymphocytic leukemia (CLL). Both TLS and neutropenia can lead to potentially life-threatening complications for patients with chronic lymphocytic leukemia undergoing antineoplastic therapy. This article focuses on diligent risk assessment, prophylaxis, early identification, monitoring, patient education, and prompt intervention for TLS and neutropenia. These are all necessary steps to reduce life-threatening complications. Guidelines are available for risk assessments for both TLS and neutropenia.

FDA-Approved Drugs for Hematological Malignancies-The Last Decade Review.

Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug

Hairy cell leukemia in kidney transplantation: lesson from a rare disorder.

We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.

Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that t

Transplant oncology and anti-cancer immunosuppressants.

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore,

Sildenafil potentiates bone morphogenetic protein signaling in pulmonary arterial smooth muscle cells and in experimental pulmonary hypertension.

OBJECTIVE: Mutations in the bone morphogenetic protein type II receptor (BMPR-II) are responsible for the majority of cases of heritable pulmonary arterial hypertension (PAH), and BMPR-II deficiency contributes to idiopathic and experimental forms of PAH. Sildenafil, a potent type-5 nucleotide-dependent phosphodiesterase inhibitor, is an established treatment for PAH, but whether sildenafil affects bone morphogenetic protein (BMP) signaling in the pulmonary circulation remains unknown. METHODS AND RESULTS: Studies were undertaken in human pulmonary arterial smooth muscle cells (PASMCs) and in

Диабетическая иммунотерапия Адаптация с BCG: Metabolic and Immune Reprogramming.

В настоящем обзоре клеточные и молекулярные механизмы, лежащие в основе мультидозы Bacille Calmette-Guérin (BCG), характеризуются как лечебная иммунная терапия для улучшения глицемии аутоиммунного диабета. Данные BCG чаще всего представляют собой данные клинических испытаний человека за последние годы. 15 годы в паре с механистическими представлениями. БЦЖ как вакцина имеет отличный послужной список в плане безопасности, который за сто лет был достигнут в области профилактики туберкулеза во всем мире, и за 36 Годы, были утверждены УЛХ при более высоких дозах для лечения рака мочевого пузыря. Н

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… This included greater levels of purine synthesis intermediates. In gene expression assays, the trial found upregulated expression of proteins controlling the pentose phosphate shunt, a pathway that branches off early in glycolysis to supply ribose-5-phosphate for biosynthesis of purines. … Aerobic glycolysis, unlike oxidative phosphorylation, drives increased flux through the pentose phosphate shunt, thereby enhancing purine biosynthesis needed for immune cell activation and rapid proliferation. …

Signaling molecules in overcirculation-induced pulmonary hypertension in piglets: effects of sildenafil therapy.

BACKGROUND: The phosphodiesterase type-5 (PDE-5) inhibitor sildenafil has been reported to improve pulmonary arterial hypertension (PAH), but the mechanisms that account for this effect are incompletely understood. Severe pulmonary hypertension has been characterized by defects in a signaling pathway involving angiopoietin-1 and the bone morphogenetic receptor-2 (BMPR-2). We investigated the effects of sildenafil on hemodynamics and signaling molecules in a piglet overcirculation-induced model of early PAH. METHODS AND RESULTS: Thirty 3-week-old piglets were randomized to placebo or sildenafi

Heat shock protein 90 and role of its chemical inhibitors in treatment of hematologic malignancies.

Heat shock protein 90 (Hsp90) is a conserved and constitutively expressed molecular chaperone and it has been shown to stabilize oncoproteins and facilitate cancer development. Hsp90 has been considered as a therapeutic target for cancers and three classes of Hsp90 inhibitors have been developed: (1) benzoquinone ansamycin and its derivatives, (2) radicicol and its derivates, and (3) small synthetic inhibitors. The roles of these inhibitors in cancer treatment have been studied in laboratories and clinical trials, and some encouraging results have been obtained. Interestingly, targeting of Hsp

Targeting mTOR and Metabolism in Cancer: Lessons and Innovations.

Cancer cells support their growth and proliferation by reprogramming their metabolism in order to gain access to nutrients. Despite the heterogeneity in genetic mutations that lead to tumorigenesis, a common alteration in tumors occurs in pathways that upregulate nutrient acquisition. A central signaling pathway that controls metabolic processes is the mTOR pathway. The elucidation of the regulation and functions of mTOR can be traced to the discovery of the natural compound, rapamycin. Studies using rapamycin have unraveled the role of mTOR in the control of cell growth and metabolism. By sen

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… Cancer cells require an abundant pool of purines and pyrimidines, which serves as building blocks for DNA and RNA synthesis. … mTORC2 also regulates purine synthesis via Akt [ 158 ]. …

Infections After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

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Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately ex

Emerging treatment options for patients with p53-pathway-deficient CLL.

Over the past 40 years, p53 has been the most widely studied protein in cancer biology. Originally thought to be an oncogene due to its stabilization in many cancers, it is now considered to be one of the most critical tumor suppressors in a cell's ability to combat neoplastic transformation. Due to its critical roles in apoptosis, cell-cycle arrest, and senescence, TP53 deletions and mutations are commonly observed and are often a portent of treatment failures and poor clinical outcomes. This is particularly true in chronic lymphocytic leukemia (CLL), as patients with p53 alterations have his

Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibito

Ryanodine receptor blockade reduces amyloid-β load and memory impairments in Tg2576 mouse model of Alzheimer disease.

In Alzheimer disease (AD), the perturbation of the endoplasmic reticulum (ER) calcium (Ca²⁺) homeostasis has been linked to presenilins, the catalytic core in γ-secretase complexes cleaving the amyloid precursor protein (APP), thereby generating amyloid-β (Aβ) peptides. Here we investigate whether APP contributes to ER Ca²⁺ homeostasis and whether ER Ca²⁺ could in turn influence Aβ production. We show that overexpression of wild-type human APP (APP(695)), or APP harboring the Swedish double mutation (APP(swe)) triggers increased ryanodine receptor (RyR) expression and enhances RyR-mediated ER

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era.

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual gen

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

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… | Oral Tablets; 2.5 mg/kg | F: 5–37% Tmax: 2 h Protein Bound: 19% Vd: 0.56–0.9 L/kg M: GI mucosa, liver (6‐thiouric acid) Elimination t 1/2 : 21 minutes (children), 47 min (adult) CL: 11 mL/min/kg E: urine Dialyzable: no | Analog of naturally occurring purines, hypoxanthine and guanine Purine antagonist … cytotoxic effects on B and T cells through impairment of DNA synthesis, leading to lymphocyte depletion in multiple sclerosis. | None reported Clofarabine | Intravenous Injection; 1 mg/mL | t 1/2 : 5.2 h Protein Bound: 47% Vd: 172 L/sq.meter M: intracellular CL: 28.8 L/h/sq. meter E: urine 49–60% | Purine …

Эффективность бортезомиба в сочетании с гипер-CVAD у взрослых с рецидивом острой лимфоболической лейкемии или положительными измеримыми остаточными заболеваниями; воздействие бортезомиба в лейкемии.

Несмотря на прогресс, достигнутый в лечении острой лимфоболической лейкемии (ОЛЛ), рецидив остается наиболее серьезной проблемой в деле улучшения прогнозирования. Оценка измеримых остаточных заболеваний (MRD) может спрогнозировать рецидив костного мозга на основе позитивности MRD. Поскольку доступ к инновационным методам лечения по-прежнему ограничен из-за высоких затрат, химиотерапия является широко используемым вариантом лечения. Об эффективности сочетания бортезомби и Hyper-CVAD сообщалось у пациентов с множественной миеломой; однако его эффективность еще не была подтверждена у пациентов, и

Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells.

Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM)