Notes

The Cross-Links involving Endoplasmic Reticulum Stress, Autophagy, and also Neurodegeneration within Parkinson's Illness.
High-grade gliomas are among the deadliest of all cancers despite standard treatments, and new therapeutic strategies are needed to improve patient outcome. Targeting the altered metabolic state of tumors with traditional chemotherapeutic agents has a history of success, and our increased understanding of cellular metabolism in the past 2 decades has reinvigorated the concept of novel metabolic therapies in brain tumors. Here we highlight metabolic alterations in advanced gliomas and their translation into clinical trials using both novel agents and already established drugs repurposed for cancer treatment in an effort to improve outcome for these deadly diseases.
High-grade gliomas are among the deadliest of all cancers despite standard treatments, and new therapeutic strategies are needed to improve patient outcome. Targeting the altered metabolic state of tumors with traditional chemotherapeutic agents has a history of success, and our increased understanding of cellular metabolism in the past 2 decades has reinvigorated the concept of novel metabolic therapies in brain tumors. Here we highlight metabolic alterations in advanced gliomas and their translation into clinical trials using both novel agents and already established drugs repurposed for cancer treatment in an effort to improve outcome for these deadly diseases.
Glioblastoma (GBM) is an intrinsically treatment-resistant tumor and has been shown to upregulate DNA damage response (DDR) components after treatment. DNA damage response signaling mediates treatment resistance by promoting cell cycle arrest in order to allow for DNA damage repair and avoid mitotic catastrophe. Therefore, targeting the DDR pathway is an attractive strategy to combat treatment resistance in GBM. In this review, we discuss the different DDR pathways and then summarize the current preclinical evidence for DDR inhibitors in GBM, as well as completed and ongoing clinical trials.
Glioblastoma (GBM) is an intrinsically treatment-resistant tumor and has been shown to upregulate DNA damage response (DDR) components after treatment. DNA damage response signaling mediates treatment resistance by promoting cell cycle arrest in order to allow for DNA damage repair and avoid mitotic catastrophe. Therefore, targeting the DDR pathway is an attractive strategy to combat treatment resistance in GBM. In this review, we discuss the different DDR pathways and then summarize the current preclinical evidence for DDR inhibitors in GBM, as well as completed and ongoing clinical trials.
Gliomas and glioblastoma comprise the majority of brain malignancies and are difficult to treat despite standard of care and advances in immunotherapy. The challenges of controlling glioma growth and recurrence involve the uniquely immunosuppressive tumor microenvironment and systemic blunting of immune responses. In addition to highlighting key features of glioma and glioblastoma composition and immunogenicity, this review presents several future directions for immunotherapy, such as vaccines and synergistic combination treatment regimens, to better combat these tumors.
Gliomas and glioblastoma comprise the majority of brain malignancies and are difficult to treat despite standard of care and advances in immunotherapy. The challenges of controlling glioma growth and recurrence involve the uniquely immunosuppressive tumor microenvironment and systemic blunting of immune responses. In addition to highlighting key features of glioma and glioblastoma composition and immunogenicity, this review presents several future directions for immunotherapy, such as vaccines and synergistic combination treatment regimens, to better combat these tumors.
The intersection of biology and technology has led to many advancements for the field of neurosurgery. Molecular developments have led to the identification of specific mutations, allowing for more accurate discussions in regard to prognosis and treatment effect. Even amid the progress from basic science benchwork, malignant gliomas continue to have a bleak natural history in lieu of the resistance to chemotherapy and the diffuse nature of the disease, leaving room for further research to discover more effective treatment modalities. Novel imaging methods, including the emerging field of radiogenomics, involve the merging of molecular and radiographic data, enabling earlier, detailed molecular diagnoses and improved surveillance of this pathology. Furthermore, surgical advancements have led to safer and more extensive resections. This review aims to delineate the various advancements in the many facets that are used daily in the care of our glioma population, specifically pertaining to its biology, imaging ioma population, specifically pertaining to its biology, imaging modalities, and perioperative adjuncts used in the operating room.
Gliomas are the most common primary brain cancer, yet are extraordinarily challenging to treat because they can be aggressive and infiltrative, locally recurrent, and resistant to standard treatments. Furthermore, the treatments themselves, including radiation therapy, can affect patients' neurocognitive function and quality of life. Noninvasive imaging is the standard of care for primary brain tumors, including diagnosis, treatment planning, and monitoring for treatment response. This article explores the ways in which advanced imaging has and will continue to transform radiation treatment for patients with gliomas, with a focus on cognitive preservation and novel biomarkers, as well as precision radiotherapy and treatment adaptation. Advances in novel imaging techniques continue to push the field forward, to more precisely guided treatment planning, radiation dose escalation, measurement of therapeutic response, and understanding of radiation-associated injury.
Gliomas are the most common primary brain cancer, yet are extraordinarily challenging to treat because they can be aggressive and infiltrative, locally recurrent, and resistant to standard treatments. Furthermore, the treatments themselves, including radiation therapy, can affect patients' neurocognitive function and quality of life. Noninvasive imaging is the standard of care for primary brain tumors, including diagnosis, treatment planning, and monitoring for treatment response. This article explores the ways in which advanced imaging has and will continue to transform radiation treatment for patients with gliomas, with a focus on cognitive preservation and novel biomarkers, as well as precision radiotherapy and treatment adaptation. Advances in novel imaging techniques continue to push the field forward, to more precisely guided treatment planning, radiation dose escalation, measurement of therapeutic response, and understanding of radiation-associated injury.
Advanced imaging techniques provide a powerful tool to assess the intratumoral and intertumoral heterogeneity of gliomas. Advances in the molecular understanding of glioma subgroups may allow improved diagnostic assessment combining imaging and molecular tumor features, with enhanced prognostic utility and implications for patient treatment. In this article, a comprehensive overview of the physiologic basis for conventional and advanced imaging techniques is presented, and clinical applications before and after treatment are discussed. An introduction to the principles of radiomics and the advanced integration of imaging, clinical outcomes, and genomic data highlights the future potential for this field of research to better stratify and select patients for standard as well as investigational therapies.
Advanced imaging techniques provide a powerful tool to assess the intratumoral and intertumoral heterogeneity of gliomas. Advances in the molecular understanding of glioma subgroups may allow improved diagnostic assessment combining imaging and molecular tumor features, with enhanced prognostic utility and implications for patient treatment. In this article, a comprehensive overview of the physiologic basis for conventional and advanced imaging techniques is presented, and clinical applications before and after treatment are discussed. An introduction to the principles of radiomics and the advanced integration of imaging, clinical outcomes, and genomic data highlights the future potential for this field of research to better stratify and select patients for standard as well as investigational therapies.
The classification, diagnosis, and biological understanding of high-grade gliomas has been transformed by an evolving understanding of glioma biology. High-grade gliomas, in particular, have exemplified the impact of molecular alterations in pathology. The discovery of mutations in a key metabolic enzyme (IDH), histone genes (H3-3A), and large-scale chromosome changes (+7/-10, 1p/19q) are examples of specific alterations that now supplant traditional histologic interpretation. Here, we review established and recently defined types of adult and pediatric high-grade gliomas with discussion of key molecular alterations that have been leveraged for subclassification, grading, or prognosis.
The classification, diagnosis, and biological understanding of high-grade gliomas has been transformed by an evolving understanding of glioma biology. selleck chemicals llc High-grade gliomas, in particular, have exemplified the impact of molecular alterations in pathology. The discovery of mutations in a key metabolic enzyme (IDH), histone genes (H3-3A), and large-scale chromosome changes (+7/-10, 1p/19q) are examples of specific alterations that now supplant traditional histologic interpretation. Here, we review established and recently defined types of adult and pediatric high-grade gliomas with discussion of key molecular alterations that have been leveraged for subclassification, grading, or prognosis.
Multiple myeloma (MM) remains incurable with high rates of relapse. New therapeutic drugs are therefore urgently needed to improve the prognosis. JaponiconeA (JA), a natural product isolated from
, has shown good anti-MM potential. A comprehensive study should therefore be conducted to identify both the
and
mechanisms of the anti-MM effects of JA.

CCK8 assays and flow cytometry were used to detect the proliferation, apoptosis, and cell cycle of MM cell lines when treated with JA.
experiments were conducted using subcutaneous xenograft mouse models. We also identified possible targets and the mechanism of JA using RNA-seq and c-Map databases, and identified the specific targets of JA in bortezomib-sensitive and -resistant MM cell lines using CETSA, DARTS, and rescue experiments. Furthermore, JA and bortezomib were used separately or together to characterize their possible synergistic effects.

, JA inhibited proliferation, and induced apoptosis and G2/M phase arrest in MM cell lines, and selectively killed primary CD138
MM cells.
, JA also demonstrated a strong anti-tumor effect with no observable toxicity. In addition, JA showed synergetic effects in combination with bortezomib, and enhanced the anti-tumor effect of bortezomib in bortezomib-resistant cells. CETSA and DARTS confirmed direct binding of JA to NF-κB inhibitor kinase beta (IKKβ), and overexpression of IKKβ or knockdown of IκBα partially rescued the apoptosis induced by JA.

JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB-induced drug resistance by inhibiting IKKβ, providing a new treatment strategy for MM patients.
JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB-induced drug resistance by inhibiting IKKβ, providing a new treatment strategy for MM patients.
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