Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor

Bruton tyrosine kinase (BTK) inhibitors have become an important therapy for untreated and previously treated patients with chronic lymphocytic leukemia (CLL). Despite improved outcomes, rare adverse events, such as invasive fungal infections, have been reported with the use of first-generation BTK inhibitors. Invasive fungal infections carry a high morbidity and mortality risk. There have been several case reports describing the association between aspergillosis and ibrutinib treatment, but none with acalabrutinib, to our knowledge. In this case report, we describe a patient with CLL who developed an intracranial Aspergillus fumigatus infection while receiving acalabrutinib

Checkpoint Inhibitors in Multiple Myeloma: Intriguing Potential and Unfulfilled Promises

Immune dysregulation and alteration of the bone marrow microenvironment allowing plasma cells to escape immune surveillance are well-known factors associated with the proliferation of clonal plasma cells and development of multiple myeloma (MM). Whilst immunotherapeutic approaches are now commonplace in a wide spectrum of malignancies, this aberration of myeloma development gives rise to the biological rationale for the use of immune checkpoint inhibitors (ICIs) in MM. However, the initial experience with these agents has been challenging with limited single agent efficacy, significant toxicity, and side effects. Herein, we review the biological and immunological aspects of MM and ICIs. We discuss the basic biology of immune checkpoint inhibitors, mechanisms of resistance, and drug failure patterns, review the published clinical trial data for ICIs in MM, and look towards the future of ICIs for MM treatment

Field Crop Responses and Management Strategies to Mitigate Soil Salinity in Modern Agriculture: A Review

The productivity of cereal crops under salt stress limits sustainable food production and food security. Barley followed by sorghum better adapts to salinity stress, while wheat and maize are moderately adapted. However, rice is a salt-sensitive crop, and its growth and grain yield are significantly impacted by salinity stress. High soil salinity can reduce water uptake, create osmotic stress in plants and, consequently, oxidative stress. Crops have evolved different tolerance mechanisms, particularly cereals, to mitigate the stressful conditions, i.e., effluxing excessive sodium (Na+) or compartmentalizing Na+ to vacuoles. Likewise, plants activate an antioxidant defense system to detoxify apoplastic cell wall acidification and reactive oxygen species (ROS). Understanding the response of field crops to salinity stress, including their resistance mechanisms, can help breed adapted varieties with high productivity under unfavourable environmental factors. In contrast, the primary stages of seed germination are more critical to osmotic stress than the vegetative stages. However, salinity stress at the reproductive stage can also decrease crop productivity. Biotechnology approaches are being used to accelerate the development of salt-adapted crops. In addition, hormones and osmolytes application can mitigate the toxicity impact of salts in cereal crops. Therefore, we review the salinity on cereal crops physiology and production, the management strategies to cope with the harmful negative effect on cereal crops physiology and production of salt stress

Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma

Despite the addition of several new agents to the armamentarium for the treatment of multiple myeloma (MM) in the last decade and improvements in outcomes, the refractory and relapsing disease continues to take a great toll, limiting overall survival. Therefore, additional novel approaches are needed to improve outcomes for MM patients. The oncogenic transcription factor MYC drives cell growth, differentiation and tumor development in many cancers. MYC protein levels are tightly regulated by the proteasome and an increase in MYC protein expression is found in more than 70% of all human cancers, including MM. In addition to the ubiquitin-dependent degradation of MYC by the 26S proteasome, MYC levels are also regulated in a ubiquitin-independent manner through the REGγ activation of the 20S proteasome. Here, we demonstrate that a small molecule activator of the 20S proteasome, TCH-165, decreases MYC protein levels, in a manner that parallels REGγ protein-mediated MYC degradation. TCH-165 enhances MYC degradation and reduces cancer cell growth in vitro and in vivo models of multiple myeloma by enhancing apoptotic signaling, as assessed by targeted gene expression analysis of cancer pathways. Furthermore, 20S proteasome enhancement is well tolerated in mice and dogs. These data support the therapeutic potential of small molecule-driven 20S proteasome activation for the treatments of MYC-driven cancers, especially MM