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Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

BH3 Mimetics in Hematologic Malignancies.

Hematologic malignancies (HM) comprise diverse cancers of lymphoid and myeloid origin, including lymphomas (approx. 40%), chronic lymphocytic leukemia (CLL, approx. 15%), multiple myeloma (MM, approx. 15%), acute myeloid leukemia (AML, approx. 10%), and many other diseases. Despite considerable improvement in treatment options and survival parameters in the new millennium, many patients with HM still develop chemotherapy‑refractory diseases and require re-treatment. Because frontline therapies for the majority of HM (except for CLL) are still largely based on classical cytostatics, the relapse

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… Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): Follow-up results from a multicentre, open-label, randomised, phase 3 trial Lancet Oncol. 2020 21 1188 1200 10.1016/S1470-2045(20)30443-5 32888452 76. Davids M.S. …

Plasma Cell Disorders

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… a wide range of options from no therapy to the use of steroids alone, or more commonly, combination chemotherapy protocols including melphalan and prednisolone (the most commonly used combination); COP (cyclophosphamide, vincristine, prednisolone); or permutations that have included dexamethasone, chlorambucil …

Cancer in pregnancy: FIGO Best practice advice and narrative review.

Cancer during pregnancy is relatively rare. The incidence is underestimated due to the lack of international registries covering both high-income and low- and middle-income countries, and is expected to rise with increasing maternal age and increasing global adoption of cell-free DNA testing for aneuploidy. Physiological changes during pregnancy often make the diagnosis challenging and delayed. Lack of experience and knowledge about this condition may also contribute to late diagnosis, suboptimal management, and occasionally inadvertent fetal and/or maternal harm. The principles of cancer mana

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… Cytarabine is the safest and can be used in the 2nd and 3rd trimesters to treat leukemia because risk to mother of delaying chemotherapy is high 85 , 86 Considered safe to use fluorouracil in the 2nd and 3rd trimesters 29 , 87 Always avoid methotrexate during pregnancy Alkylating agents: busulfan, chlorambucil …

Clinical Dilemmas in the Treatment of Elderly Patients Suffering from Hodgkin Lymphoma: A Review.

Elderly patients make up a significant number of cases of newly diagnosed Hodgkin lymphoma. However, unlike in young patients, the outcomes of elderly patients are poor, and they are under-represented in phase III trials. Prior to treatment initiation, geriatric assessment should ideally be performed to address the patient's fitness and decide whether to pursue a curative or palliative approach. The ABVD regimen is poorly tolerated in unfit patients, with high treatment-related mortality. Alternative chemotherapy approaches have been explored, with mixed results obtained concerning their feasi

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… ; IFRT—involved-field radiation therapy; VEPEMB—vinblastine, cyclophosphamide, procarbazine, bleomycin, prednisone, mitoxantrone and etoposide; CHOP—cyclophosphamide, doxorubicin, vincristine and prednisolone; PVAG—prednisone, vinblastine, doxorubicin and gemcitabine; BV—brentuximab vedotin; ChlVPP—chlorambucil …

Medicinal Plants with Anti-Leukemic Effects: A Review.

Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient's survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half

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… Although chemotherapeutic drugs such as cyclophosphamide, fludarabine, prednisone, chlorambucil and doxorubicin are used clinically to treat leukemia, they are used in combination instead of being used as single drugs and often do not improve the patient’s overall survival rate. …

Chronic Kidney Disease: Strategies to Retard Progression.

Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the follo

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… D + calcium | Diuretics ↑Oncotic pressure (albumin infusion) Lipid lowering Anticoagulation (prevent or treat thromboembolism) | Steroids | Calcineurin inhibitors | Antimetabolite | Alkalizing agents | Anti-CD20 | PP | Prednisolone ACTH | Cyclosporine Tacrolimus | Mycophenolate Azathioprine | CYC Chlorambucil …

RESEARCH COMMUNICATIONS OF THE 34th ECVIM-CA CONGRESS.

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… interactions at play within academic hospitals and within the broader University system ESVIM‐O‐15 | 17.30‐17.45 | Knopf | Causes and outcome of systemic inflammatory response syndrome (SIRS) in dogs – analysis of 172 cases ESVIM‐O‐16 | 17.45‐18.00 | Bouzouraa | Long‐term follow‐up of dogs treated with a chlorambucil‐prednisolone …

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies.

In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T

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… ASCT, autologous stem cell transplant; BCMA, B cell maturation antigen; Bu, busulfan; CAR T cell, chimeric antigen receptor modified T cell; CP, chlorambucil, prednisone; CRS, cytokine release syndrome; Cy, cyclophosphamide; Flu, fludarabine; G, grade; LDC, lymphodepleting conditioning; Mel, melphalan …

Research Progress in Pharmacological Targeted Therapy for Myasthenia Gravis.

Myasthenia gravis (MG) is a disorder of neuromuscular junction transmission that is mediated by autoantibodies and depends on T cell help, causing fatigable muscle weakness. Limitations of conventional first-line treatments, including long-term adverse effects and inadequate control of refractory disease, have driven targeted therapy to the forefront of MG research. This narrative review summarizes second-line and later-line targeted biological and cellular therapies, covering agents directedat B and T cells, complement inhibitors, neonatal Fc receptor (FcRn) antagonists and cytokine inhibitor

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… Obinutuzumab plus chlorambucil in a patient with severe Myasthenia gravis and chronic lymphocytic leukemia. J Neuromuscul Dis . 2017;4(3):251–257. doi: 10.3233/jnd-170211 61. Kang C, Blair HA. Ofatumumab: a review in relapsing forms of multiple sclerosis. …

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

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… Reduced DNA Double Strand Breaks in Chlorambucil Resistant Cells Are Related to High DNA-PKcs Activity and Low Oxidative Stress. Toxicology 193 (1–2), 137–152. 10.1016/J.TOX.2003.08.013 Briere D., Sudhakar N., Woods D. M., Hallin J., Engstrom L. D., Aranda R., et al. (2018). …

Co-Encapsulation of Multiple Antineoplastic Agents in Liposomes by Exploring Microfluidics.

The inherent complexity of cancer proliferation and malignancy cannot be addressed by the conventional approach of relying on high doses of a single powerful anticancer agent, which is associated with poor efficacy, higher toxicity, and the development of drug resistance. Multiple drug therapy (MDT) rationally designed to target tumor heterogeneity, block alternative survival pathways, modulate the tumor microenvironment, and reduce toxicities would be a viable solution against cancer. Liposomes are the most suitable carrier for anticancer MDT due to their ability to encapsulate both hydrophil

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… Doxorubicin–Cyclophosphamide–Paclitaxel 8 | Doxorubicin–Cyclophosphamide–Fluorouracil 9 | Methotrexate–Cyclophosphamide–Fluorouracil 10 | Epirubicin–Cyclophosphamide–Fluorouracil 11 | Doxorubicin–Cyclophosphamide–Docetaxel 12 | Cervical | Gemcitabine–Cisplatin 13 | Carboplatin–Paclitaxel 14 | Chronic Lymphocytic Leukemia | Chlorambucil–Prednisone …

A 16-week progressive exercise training intervention in treatment-naïve chronic lymphocytic leukaemia: a randomised-controlled pilot study.

BackgroundChronic lymphocytic leukaemia (CLL) typically presents with asymptomatic, early-stage disease that is monitored until disease progression ('treatment-naïve' CLL). The objective of this pilot study was to assess the feasibility and preliminary safety of an exercise program in treatment-naïve CLL. We also sought to preliminarily assess the impact of the exercise program on disease activity, as it has been proposed that exercise training may reduce disease outgrowth in treatment-naïve CLL.MethodsA total of 40 treatment-naïve CLL patients were recruited into this randomised-controlled pi

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… Chlorambucil in indolent chronic lymphocytic leukemia . New Engl J Med . ( 1998 ) 338 : 1506–14 . doi: 10.1056/NEJM199805213382104 9593789 6 Hoechstetter MA Busch R Eichhorst B Bühler A Winkler D Eckart MJ . …

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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… . | None reported Chlorambucil | Oral Tablets; 0.1 mg/kg | A: 100% F: 70%–80% Tmax: 1 hr Protein Bound: 99% Vd: 0.3 L/kg M: Liver Elimination t 1/2 : 1.5 h CL: 492 ± 160 ng/mL E: Urine (20–60% metabolites) Dialyzable: No | Alkylating substances from the nitrogen mustard family that cross‐linking DNA …

Vaccination of Immunocompromised Cats.

Immunocompromise is a common condition in cats, especially due to widespread infections with immunosuppressive viruses, such as feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), but also due to chronic non-infectious diseases, such as tumours, diabetes mellitus, and chronic kidney disease, as well as treatment with immunosuppressive drugs, such as glucocorticoids, cyclosporins, or tumour chemotherapy. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from eleven European countries, discusses

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… Glucocorticoids, cyclosporine, azathioprine, chlorambucil, and mycophenolate in dogs and cats: Clinical uses, pharmacology, and side effects. Vet. Clin. N. Am. Small Anim. Pract. 2022;52:797–817. doi: 10.1016/j.cvsm.2022.01.009. 121. Tizard I.R. …

Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches.

Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for

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… They are categorized into six principal types: nitrogen mustards (e.g., mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil), ethylenamine and methylamine derivatives, alkylsulfonates, nitrosoureas, triazines, and platinum-containing antineoplastic agents. …

The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.

The bidirectional crosstalk between the nervous system and tumors has emerged as a transformative new frontier in both precision oncotherapy and mechanism-driven cancer pain management. Marine natural products with inherent neuroactive properties exhibit unparalleled intervention advantages for targeting this complex pathophysiological axis. Herein, we systematically and prospectively dissect the multi-layered bidirectional communication between the nervous system and malignancies, comprehensively summarize the pivotal contributions of marine-derived bioactive molecules to advances in neurosci

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… Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N. Engl. J. Med. 2000;343:1750–1757. doi: 10.1056/nejm200012143432402. 92. Saven A., Piro L. Newer purine analogues for the treatment of hairy-cell leukemia. N. Engl. J. …

Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BackgroundCytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies.Main bodyCIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary

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… Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–10. 19. Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, et al. …

Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus

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… Patients treated with a continuous oral regimen consisting of As 2 O 3 , chlorambucil, and vitamin C were those with relapsed/refractory MCL who were not eligible for high-dose chemotherapy and had received previous regimens. …

Antibodies to watch in 2018.

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody

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… Ublituximab is also under investigation in the Phase 3 UNITY-CLL study ( NCT02612311 ) to evaluate the efficacy and safety of the combination of ublituximab plus TGR-1202 (PI3K inhibitor), compared to obinutuzumab (anti-CD20 antibody) plus chlorambucil, ublituximab alone or TGR-1202 alone in CLL patients …