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Function: require_once
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Filename: controllers/Detail.php
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Function: _error_handler
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
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Function: require_once
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
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Filename: models/Detail_model.php
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File: /var/www/html/application/models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: str_replace
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: require_once
Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by a wide range of tumor-induced alterations, which affect both the innate and adaptive arms of the immune response, and accumulate during disease progression. In recent years, the development of targeted therapies, such as the B-cell receptor signaling inhibitors and the Bcl-2 protein inhibitor venetoclax, has dramatically changed the treatment landscape of CLL. Despite their remarkable anti-tumor activity, targeted agents have some limitations, which include the development of drug resistance mechanisms and the inferior efficacy observed in high-risk patients. Therefore, additional treatments are necessary to obtain deeper responses and overcome drug resistance. Allogeneic hematopoietic stem cell transplantation (HSCT), which exploits immune-mediated graft--leukemia effect to eradicate tumor cells, currently represents the only potentially curative therapeutic option for CLL patients. However, due to its potential toxicities, HSCT can be offered only to a restricted number of younger and fit patients. The growing understanding of the complex interplay between tumor cells and the immune system, which is responsible for immune escape mechanisms and tumor progression, has paved the way for the development of novel immune-based strategies. Despite promising preclinical observations, results from pilot clinical studies exploring the safety and efficacy of novel immune-based therapies have been sometimes suboptimal in terms of long-term tumor control. Therefore, further advances to improve their efficacy are needed. In this context, possible approaches include an earlier timing of immunotherapy within the treatment sequencing, as well as the possibility to improve the efficacy of immunotherapeutic agents by administering them in combination with other anti-tumor drugs. In this review, we will provide a comprehensive overview of main immune defects affecting patients with CLL, also describing the complex networks leading to immune evasion and tumor progression. From the therapeutic standpoint, we will go through the evolution of immune-based therapeutic approaches over time, including i) agents with broad immunomodulatory effects, such as immunomodulatory drugs, ii) currently approved and next-generation monoclonal antibodies, and iii) immunotherapeutic strategies aiming at activating or administering immune effector cells specifically targeting leukemic cells (e.g. bi-or tri-specific antibodies, tumor vaccines, chimeric antigen receptor T cells, and checkpoint inhibitors).
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http://dx.doi.org/10.3389/fimmu.2020.594556 | DOI Listing |
Cent Eur J Immunol
November 2024
Institute of Biology, University of Szczecin, Szczecin, Poland.
Recent advances in immunology have challenged the conventional division of T-lymphocyte function by uncovering novel subpopulations with diverse roles and characteristics. This article reviews these discoveries and their implications for understanding immune regulation and disease pathogenesis. Innovative techniques have enabled the identification of previously unrecognized T-lymphocyte subsets, disrupting the classical classification system.
View Article and Find Full Text PDFEur Urol Open Sci
January 2025
Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Introduction And Objective: Imiquimod (IQ) is an immunomodulator used in the management of penile intraepithelial neoplasia (PeIN) lesions. However, IQ treatment may be associated with bothersome side effects (SEs). To date, studies reporting on this morbidity and evaluating predictors of response to IQ are scarce and included small cohorts.
View Article and Find Full Text PDFTransl Cancer Res
November 2024
Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, China.
Background: Ovarian cancer (OC) is a highly aggressive and often fatal disease that frequently goes undetected until it has already metastasized. The classic treatment for OC involves surgery followed by chemotherapy. However, despite the effectiveness of surgery, relapse is still a common occurrence.
View Article and Find Full Text PDFFront Oncol
December 2024
Research & Development, SMURF-Therapeutics, Inc., Providence, RI, United States.
The SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) has emerged as a critical regulator in cancer biology, modulating the stability of Hypoxia-Inducible Factor 1-alpha (HIF1α) and influencing a network of hypoxia-driven pathways within the tumor microenvironment (TME). SMURF2 targets HIF1α for ubiquitination and subsequent proteasomal degradation, disrupting hypoxic responses that promote cancer cell survival, metabolic reprogramming, angiogenesis, and resistance to therapy. Beyond its role in HIF1α regulation, SMURF2 exerts extensive control over cellular processes central to tumor progression, including chromatin remodeling, DNA damage repair, ferroptosis, and cellular stress responses.
View Article and Find Full Text PDFNeural Regen Res
December 2024
Department of Pharmacology, Institute of Medical Sciences, College of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors, rigidity, and slowed movements. A key feature of Parkinson's disease is the accumulation of misfolded α-synuclein, forming insoluble Lewy bodies in the substantia nigra pars compacta, which contributes to neurodegeneration. These α-synuclein aggregates may act as autoantigens, leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.
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