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Abstracts from the 8th Drug Hypersensitivity Meeting (DHM)

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Unlocking the Potential of Ganoderma lucidum (Curtis): Botanical Overview, Therapeutic Applications, and Nanotechnological Advances.

Background:Ganoderma lucidum (GL), commonly known as the "Lingzhi" or "Reishi" mushroom, has long been recognized for its potential health benefits and medicinal properties in traditional Chinese medicine. The unique potential combination of bioactive compounds present in GL, such as triterpenoids, polysaccharides, and peptides, has inspired interest in leveraging their therapeutic potential In recent years, the emerging field of nanotechnology has opened up new possibilities for using the remarkable properties of GL at the nanoscale. Objetive: The main objective of this review is to explore t

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… For example, in a preclinical study, co-encapsulation of GLTs and some chemotherapeutic drugs (e.g., Paclitaxel, Doxorubicin, Cisplatin, 5-Fluorouracil, Gemcitabine, Etoposide, and Vinblastine) within nanoparticles resulted in enhanced cytotoxicity against cancer cells compared to the individual treatments …

Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.

Cancer stem cells (CSCs) drive tumor progression, therapy resistance, and metastasis through unique membrane biology, glycosylation patterns, and metabolic adaptations. CSCs exhibit a distinct glycocalyx profile enriched in hyaluronan, heparan sulfate, and sialylated glycans, facilitating immune evasion, adhesion, and survival. Key signaling pathways-Wnt/β-catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR-regulate CSC stemness and therapeutic resistance. Emerging biomarkers (CD44, CD133, ALDH1, EpCAM) and targeted therapies (CAR-T cells, miRNA modulation, lipid metabolism inhibit

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… LY2510924, a potent and selective CXCR4 antagonist, has been investigated for the phase II study of renal cell carcinoma and small-cell lung cancer in the combination of sunitinib and carboplatin/etoposide respectively ( Hainsworth et al., 2016 ). …

Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.

Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key fa

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospita

How to Treat Melanoma? The Current Status of Innovative Nanotechnological Strategies and the Role of Minimally Invasive Approaches like PTT and PDT.

Melanoma is the most aggressive type of skin cancer, the incidence and mortality of which are increasing worldwide. Its extensive degree of heterogeneity has limited its response to existing therapies. For many years the therapeutic strategies were limited to surgery, radiotherapy, and chemotherapy. Fortunately, advances in knowledge have allowed the development of new therapeutic strategies. Despite the undoubted progress, alternative therapies are still under research. In this context, nanotechnology is also positioned as a strong and promising tool to develop nanosystems that act as drug ca

The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions.

Chimeric antigen receptor (CAR)-T cell therapy is effective in the treatment of refractory/relapsed (r/r) hematological malignancies (r/r B-cell lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma). In addition, it is being explored as a treatment option for solid tumors. As of 31 March 2022, seven CAR-T therapies for hematological malignancies have been approved worldwide. Although CAR-T therapy is an effective treatment for many malignancies, it also causes adverse effects. The incidence of cytokine release syndrome (CRS), the most common adverse reaction after infusion of CAR-T ce

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… Etoposide should only be used in patients with late-onset HLH/MAS who are refractory to tocilizumab ( Maus et al., 2020 ). …

Pharmacotherapy of Generalized Myasthenia Gravis with Special Emphasis on Newer Biologicals.

Myasthenia gravis (MG) is a chronic, fluctuating, antibody-mediated autoimmune disorder directed against the post-synaptic neuromuscular junctions of skeletal muscles, resulting in a wide spectrum of manifestations ranging from mild to potentially fatal. Given its unique natural course, designing an ideal trial design for MG has been wrought with difficulties and evidence in favour of several of the conventional agents is weak as per current standards. Despite this, acetylcholinesterases and corticosteroids have remained the cornerstones of treatment for several decades with intravenous immuno

Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this r

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… ICANS Immune effector cell-associated neurotoxicity syndrome, Refs References, ALL Acute lymphoblastic leukemia, NHL Non-Hodgkin lymphoma, MCL Mantle cell lymphoma, MM Multiple myeloma, CLL Chronic lymphocytic leukemia, NR No report, m Months, d Days, h Hours, Cy Cyclophosphamide, Flu Fludarabine, E Etoposide …

Antibody-Drug Conjugates for Cancer Therapy.

Antibody-drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each co

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

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… Among outcomes: assessment of biomarkers | ( 79 ) Notch, bispecific anti-DLL4 x anti-VEGF mAb: OMP-305B83 | NCT02298387 (phase I): dose escalation and expansion study in solid tumors | Anti-Notch 2/3 mAb: tarextumab/OMP-59R5 | NCT01859741 (phase Ib/II): with etoposide and platinum therapy in untreated …

Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy.

In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct

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… . *,** Abbreviations: 5-FU, 5-fluorouracil; AML, acute myeloid leukemia; ASCT, autologous stem cell transplantation; BEAM, carmustine + etoposide + cytarabine + melphalan; CEA, carcinoembryonic antigen; DLBCL, diffuse large B-cell lymphoma; EGFR, epidermal growth factor receptor; EPCAM, epithelial cell …

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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Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

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… ‐mediated lactylation of Nijmegen breakage syndrome protein 1 (NBS1) at K388 facilitated the assembly of the DNA damage repair complex MRE11‐RAD50‐NBS1 (MRN) and various HR repair proteins at DNA double‐strand break sites, promoting DNA repair and tolerance to chemotherapy agents like cisplatin and etoposide …

The Development of Novel Therapies for Chronic Lymphocytic Leukaemia in the Era of Targeted Drugs.

Over the past decade, chronic lymphocytic leukaemia (CLL) treatment has shifted from chemoimmunotherapy to targeted oral agents, predominantly Bruton's tyrosine kinase inhibitors (BTKis) and the BCL-2 inhibitor venetoclax. These therapies have significantly improved outcomes and are now established as first-line treatment options. However, CLL remains incurable, and resistance or intolerance to both drug classes (double-refractory disease) is an emerging challenge. This has driven the development of novel therapeutic strategies, including non-covalent BTKis such as pirtobrutinib and nemtabruti

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… The drug was studied alone or in combination with itacitinib (Janus kinase 1 inhibitor) or CIT with rituximab, ifosfamide, carboplatin, and etoposide in patients with RR B-cell malignancies (# NCT02018861 ) [ 113 ]. …

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

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… a D2C7-IT + 2141-V11 | I | 46 | R | Assessment of safety and efficacy in resected recurrent glioblastoma | NCT06455605 | n/a D2C7-IT & 2141-V11 | I/II | 50 | R | Determination of safety and efficacy in newly diagnosed glioblastoma | NCT05734560 | n/a Indoximod +/- TMZ +/- RT +/- Cycliphophamide +/- Etoposide …

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then,

CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1's molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotrans

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal