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Infiltrative and inflammatory systemic disorders involving the pituitary gland.

The hypothalamic-pituitary region can be affected by a wide and heterogeneous group of infiltrative and inflammatory disorders, including granulomatous, histiocytic, storage, infectious, non-pituitary neoplastic, and autoimmune or inflammatory conditions collectively grouped as hypophysitis. Although individually rare, these disorders are increasingly recognized due to growing awareness, wider use of pituitary imaging, and the emergence of immune checkpoint inhibitor-induced hypophysitis. They typically present with hypopituitarism (often including arginine vasopressin deficiency, which, parti

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… involvement associated with hypogonadism ( C , sagittal post-contrast T1-weighted image; D , coronal post-contrast T1-weighted image; E , coronal T2-weighted image showing a hypothalamic lesion with mild surrounding edema; arrows), which progressively decreased following treatment with rituximab and chlorambucil …

Extracellular Vesicles in Chronic Lymphocytic Leukemia: Tumor Microenvironment Messengers as a Basis for New Targeted Therapies?

In addition to intrinsic genomic and nongenomic alterations, tumor progression is also dependent on the tumor microenvironment (TME, mainly composed of the extracellular matrix (ECM), secreted factors, and bystander immune and stromal cells). In chronic lymphocytic leukemia (CLL), B cells have a defect in cell death; contact with the TME in secondary lymphoid organs dramatically increases the B cells' survival via the activation of various molecular pathways, including the B cell receptor and CD40 signaling. Conversely, CLL cells increase the permissiveness of the TME by inducing changes in th

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… The cytostatic agents include chlorambucil, fludarabine, and bendamustine. …

Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions.

Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib

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… Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment‐naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial . …

Chronic pruritus: a narrative review.

Chronic pruritus encompasses a manifestation of several cutaneous, allergic, infectious, neurological, psychological, and systemic conditions, whose etiological investigation and therapeutic strategy can be challenging. This comprehensive review aims to enhance the understanding of pruritus by highlighting important elements in its pathogenesis, including keratinocytes, Merkel cells and mast cells, nerve fibers, histaminergic and nonhistaminergic pathways, and the interaction of itch signals with the central nervous system. Diagnostic evaluation of chronic pruritus may require a meticulous app

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b

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… Pre-clinical studies using VitC in combination with chemotherapy and radiation therapy In pre-clinical models, high-dose VitC is reported to enhance the effectivity of a wide variety of chemotherapeutics such as carboplatin [ 63 , 89 ], cisplatin [ 51 , 89 , 100 – 103 , 179 , 180 ], chlorambucil [ 181 …

Canadian Society of Nephrology Commentary on the Evolving Kidney Disease Improving Global Outcomes Adult Glomerulonephritis Guidelines.

Purpose of reviewThe purpose of this commentary is to address the challenges of implementing the evolving Kidney Disease Improving Global Outcomes (KDIGO) glomerulonephritis (GN) guidelines within the Canadian health care context, highlighting barriers to adoption of the guidelines and discussing contextual issues unique to Canada.Sources of informationThe KDIGO 2021 guidelines with 2024 updates in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and lupus nephritis, as well as the 2025 updated guideline for immunoglobulin A (IgA) nephropathy.MethodsA Canadian Society of Nephro

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… A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int. 1995;48(5):1600-1604. 25. Howman A, Chapman TL, Langdon MM, et al. Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial. …

Consensus recommendations from the 2024 International Follicular Lymphoma Scientific Workshop.

AbstractFollicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation's biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to di

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… 31 Salles G Mounier N de Guibert S Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study Blood 112 13 2008 4824 4831 18799723 10.1182/blood-2008-04-153189 32 Herold M Haas A Srock S Rituximab added to first-line mitoxantrone, chlorambucil …

Pharmacogenomics and Big Data in medical oncology: developments and challenges.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient's response to various drugs with the aim to minimize tria

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… Drug class | Representative agents | Cell cycle effect/properties | Commonly targeted cancers | References Alkylating agents | Carboplatin, Cisplatin Chlorambucil, Cyclophosphamide Dacarbazine, Melphalan, Oxaliplatin, Temozolomide | DNA adduct, cell arrest in G2 phase, angiogenesis inhibitor, hypoxic …

Immunotherapeutic approaches for systemic lupus erythematosus: early overview and future potential.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Current SLE therapies include immunosuppressants, antimalarial drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, but these treatments can cause substantial toxicities to organs and may not be effective for all patients. In recent years, significant progress has been made in the treatment of SLE using immunotherapy, including Benlysta and Saphnelo. These advances in immunotherapy hold promise for SLE patients, providing new therapeutic options that may offer better clinical benefit and effectiveness. S

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… Obinutuzumab is a humanized and glycoengineered type II anti-CD20 mAb indicated for chronic lymphocytic leukemia (CLL) combined with chlorambucil therapy and for follicular lymphoma (FL) in combination with bendamustine [ 53 ]. …

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified

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… ‘Active’ antineoplastic treatment was defined as patients having received anticancer therapy within 30 days prior to COVID-19 diagnosis; therapies were classified as conventional chemotherapy (includes intensive and standard dosing), low-intensity chemotherapy (includes Single-agent hydroxyurea, chlorambucil …

Polycythemia Vera: Barriers to and Strategies for Optimal Management.

Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors. On

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… It demonstrated remarkable overall survival (OS) in the arm treated with VS (median 13.9 years) compared to patients treated with chlorambucil (8.9 years) or phosphorus-32 (11.8 years). …

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

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… cancer, glioblastoma Elotuzumab | 5 SLAMF7 | Multiple myeloma (MM) Gemtuzumab ozogamicin | CD33 | Acute myeloid leukemia (AML) Inotuzumab ozogamicin | CD22 | Acute Lymphoblastic Leukemia (ALL) Mogamulizumab-kpkc | 6 CCR4 | Mycosis fungoides, Sézary syndrome Obinutuzumab | CD20 | In combination with chlorambucil …

Parthenolide: pioneering new frontiers in hematological malignancies.

Hematological malignancies are the fifth most prevalent cancer category in developed countries, presenting significant treatment challenges. The side effects of chemotherapy and its non-selective nature have led researchers to explore combination therapies to enhance efficacy and improve patient outcomes. Parthenolide (PTL) emerges as a promising candidate, being the first small molecule identified for its selective action against leukemic stem cells. This article provides an overview of PTL's effects and its potential as a complementary treatment for hematological malignancies. A systematic s

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… Chlorambucil has been the standard treatment for CLL for many years. Nevertheless, using this drug on its own does not markedly improve patients’ overall survival rates. …

New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.

Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a rel

Neutropenic events associated with new anticancer treatments, from pathophysiology to practice: a scoping review-NEW Group (Neutropenic Events Working Group).

INTRODUCTION: New anticancer agents are increasingly being prescribed, either in combination or as a replacement or maintenance therapy after conventional chemotherapy. Although they present certain previously unknown complications, they are also responsible for more classic hematological toxicities, such as neutropenia. Unlike conventional chemotherapy, the comprehension and management of NAN (Neutropenia Associated with Novel anticancer agent) is currently poorly codified and understood. METHODS: A literature scoping review was conducted by the NEW Group (Neutropenic Events multidisciplinar

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… Zucca E, Conconi A, Laszlo D et al (2013) Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 randomized study. …

Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complica

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… Table 2 A list of chemotherapy well-recognized for inducing mucosal injury Class of chemotherapy | Chemotherapeutic agents Alkylating agents | Busulfan Chlorambucil Melphalan Cisplatin Anthracyclines | Doxorubicin Daunorubicin Antimetabolites | Cytarabine Methotrexate 5-Fluorouracil Antitumors | Actinomycin-D …

Advances in Gold Nanoparticle-Based Combined Cancer Therapy.

According to the global cancer observatory (GLOBOCAN), there are approximately 18 million new cancer cases per year worldwide. Cancer therapies are largely limited to surgery, radiotherapy, and chemotherapy. In radiotherapy and chemotherapy, the maximum tolerated dose is presently being used to treat cancer patients. The integrated development of innovative nanoparticle (NP) based approaches will be a key to address one of the main issues in both radiotherapy and chemotherapy: normal tissue toxicity. Among other inorganic NP systems, gold nanoparticle (GNP) based systems offer the means to fur

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… GNP: Gold Nanoparticle; PAC: Paclitaxel; TNF: Tumor Necrosis Factor; PEG: Polyethylene Glycol; DOX: Doxorubicin; BLM: Bleomycin; CIS: Cisplatin; GLC: Glucose; PDC: Peptide-drug-conjugate containing chlorambucil, melphalan, or bendamustine; 5-FU: 5-Fluorouracil; GSH: Glutathione; CS: Chitosan; RGD: arginyl-glycyl-aspartic …

A comprehensive update of extracutaneous involvement of mycosis fungoides: A narrative review of literature.

Mycosis fungoides, the most prevalent subtype of cutaneous T-cell lymphoma, primarily targets areas of the skin that of not exposed to sunlight. Nevertheless, it can involve extracutaneous tissues at any disease stage, especially during its advanced phases. Research suggests that all extracutaneous organs might be susceptible, though such cases are more commonly reported in autopsy studies and less so in clinical setting. The most recent comprehensive review of such extracutaneous manifestations in mycosis fungoides occurred almost a decade ago. With the aim of enhancing clinicians' understand

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… However, it is important to note that the nail involvement alone in CTCL should not be considered an independent criterion for initiating systemic treatment unless otherwise indicated. [ 141 ] Other treatments include PUVA, chlorambucil, and radiation therapy. [ 142 , 143 , 145 ] 2.10. …

Targeted Hybrid Nanocarriers as Co-Delivery Systems for Enhanced Cancer Therapy.

Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects i

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… Classes of drugs | Examples in each Class | Target site | Mechanism of action | Organ/cancer Alkylating agents* | Altretamine, bendamustine, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, melphalan, oxaliplatin, temozolomide | Nucleus | Destroys …

Therapeutic Antibodies in Cancer Treatment in the UK.

The growing understanding of the molecular mechanisms of carcinogenesis accelerated the development of monoclonal therapeutic antibodies to specifically target multiple cancer pathways. Recombinant protein therapeutics now constitute a large proportion of yearly approved medicines. Oncology, autoimmune diseases and to a smaller degree the prophylaxis of organ transplant rejection are their main application areas. As of the date of this review, 37 monoclonal antibody products are approved for use in cancer treatments in the United Kingdom. Currently, the antibody therapeutics market is dominate

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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 72. Sehn L.H. …