Racial/Ethnic Disparities and Immunotherapeutic Advances in the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains one of the leading causes of death among many associated liver diseases. Various conventional strategies have been utilized for treatment, ranging from invasive surgeries and liver transplants to radiation therapy, but fail due to advanced disease progression, late screening/staging, and the various etiologies of HCC. This is especially evident within racially distinct populations, where incidence rates are higher and treatment outcomes are worse for racial/ethnic minorities than their Caucasian counterparts.

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant (L.) Dunal.

Cancer represents the second most deadly disease and one of the most important public health concerns worldwide. Surgery, chemotherapy, radiation therapy, and immune therapy are the major types of treatment strategies that have been implemented in cancer treatment. Unfortunately, these treatment options suffer from major limitations, such as drug-resistance and adverse effects, which may eventually result in disease recurrence.

Blocking PCNA interaction with NKp44 enhances primary natural killer cell-mediated lysis of triple-negative breast cancer cells.

Among the innate immune cells, natural killer cells (NK) serve its role in cytolytic targeting against infected and cancerous cells. NK function is regulated by an intricate balance of signals from interactions between activating and inhibitory NK receptors and ligands expressed on target cells. As an immune evasion strategy, cancer cells, particularly triple-negative breast cancer cells (TNBCs), express ligands that interact with NK receptors to inhibit NK cell cytolytic function.

Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL).

Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands.

NK Cell Isolation and Cytotoxicity by Radioactive Chromium Release Assay and DELFIA-EuTDA Cytotoxicity Assay.

Cytotoxicity assays are important in vitro tools to measure the lysis of desired target cells via an effector immune cell of choice. Specific lysis of the target cells can be determined by labeling the target cells with a radioactive isotope or fluorescent molecule, co-incubating it with an effector cell, then measuring the release of the labeled molecule in the supernatant. Here, we describe and compare different cell cytotoxicity assays using a chromium-51 (Cr) release and DELFIA EuTDA fluorescent assay using K562 as the target cells and peripheral blood mononuclear cell (PBMC) derived natural killer (NK) cells as the effector cells.

The Many Faces of Innate Immunity in SARS-CoV-2 Infection.

The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia.

Novel Magnetic Resonance Imaging Classification of Osteochondritis Dissecans of the Knee: A Reliability Study.

Background: Current advanced imaging classification systems for osteochondritis dissecans (OCD) of the knee grade severity of disease by identifying certain lesion characteristics. The most widely used are the Hefti and Nelson systems. A novel classification presents a simpler 3-group approach to diagnose knee OCD by magnetic resonance imaging (MRI), compared with the Hefti (5-group) and Nelson (4-group) classifications.

Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer.

Natural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity.

The effect of varying degrees of compression from elastic vs plastic wrap on quadriceps intramuscular temperature during wetted ice application.

The aim of this study was to evaluate and compare the effectiveness of wetted ice bag, applied with high compression elastic wrap or held in place with low compression plastic wrap, on reducing vastus lateralis intramuscular temperature and skin surface temperature. Ten healthy male participants had wetted ice packs applied to a standardized area on the anterior aspect of the quadriceps simultaneously to both legs for 30 minutes. The ice pack was secured with high compression (elastic wrap) to the left anterior thigh (60.

Is Anteromedial Drilling Safe in Transphyseal Anterior Cruciate Ligament Reconstruction in Adolescents with Growth Remaining?

Background: Previous reports of transphyseal drilling in anterior cruciate ligament (ACL) reconstruction have demonstrated good clinical outcomes without subjective changes in further skeletal development. The purpose of this study is to evaluate radiographic changes during continued growth following a transphyseal ACL reconstruction using an anteromedial femoral (AM) drilling technique in patients with >18 months of growth remaining.

Methods: A review of consecutive adolescents who underwent a soft tissue transphyseal ACL reconstruction using an AM drilling technique was performed.

Impact of the Microbiome on the Immune System.

Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one.

Blocking LLT1 (CLEC2D, OCIL)-NKRP1A (CD161) interaction enhances natural killer cell-mediated lysis of triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is the most invasive form of breast cancer due to an absence of estrogen (ER), progesterone (PR), and human epidermal growth factor-2 (HER2) receptors on the cell surface. TNBC accounts for approximately 12 to 20 percent of all breast cancer cases. The absence of ER, PR, and HER2 receptors on TNBCs and its ability to develop drug resistance renders it difficult to eradicate or retrogress tumor growth with hormonal therapy and chemotherapy.

A novel ligand on astrocytes interacts with natural cytotoxicity receptor NKp44 regulating immune response mediated by NK cells.

NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions.

Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction.

Prostate cancer is the most common type of cancer diagnosed and the second leading cause of cancer-related death in American men. Natural Killer (NK) cells are the first line of defense against cancer and infections. NK cell function is regulated by a delicate balance between signals received through activating and inhibitory receptors.

Blimp-1/PRDM1 regulates the transcription of human CS1 (SLAMF7) gene in NK and B cells.

CS1 (CRACC/CD319/SLAMF7) is a member of SLAM (Signaling Lymphocyte Activation Molecule) family receptors and is expressed on NK cells, a subset of CD8(+) T lymphocytes, activated monocytes, mature dendritic cells and activated B cells. In NK cells, CS1 signaling induces cytolytic function of NK cells against targets whereas in B cells CS1 induces proliferation and autocrine cytokine production. CS1 is upregulated in multiple myeloma cells and contributes to clonogenic growth and tumorigenicity.

Virulence Factors Contributing to Pathogenicity of Candida tropicalis and Its Antifungal Susceptibility Profile.

The incidence of invasive candidiasis has increased over the past few decades. Although Candida albicans remains by far the most common species encountered, in recent years shift towards non-albicans Candida species like Candida tropicalis is noted. Here in this study we determined the virulence factors and antifungal susceptibility profile of 125 C.

CS1 (SLAMF7) inhibits production of proinflammatory cytokines by activated monocytes.

Objective And Design: CS1 (CRACC, CD319, SLAMF7) is a member of the Signaling Lymphocyte Activation Molecule family expressed on immune cells mediating host defense. CS1 is a self-ligand and has both activating and inhibitory functions in Natural Killer cells. However, the function of CS1 in human monocytes is currently unknown.

Novel interaction between proliferating cell nuclear antigen and HLA I on the surface of tumor cells inhibits NK cell function through NKp44.

NK cell function is closely regulated by numerous inhibitory and activating receptors binding corresponding ligands on the surface of target cells, providing vital first line defenses against infections and cancer. NKp44, originally discovered as an activating NK cell receptor, was recently found to elicit inhibitory effects on NK cell effector function through recognition of cell surface PCNA. Other reports have pointed to potential associations between NKp44 and HLA I molecules, as well as HLA I and Damage Associated Molecular Pattern molecules (DAMPs) on the surface of tumor cells.

Abnormal tibiofemoral contact stress and its association with altered kinematics after center-center anterior cruciate ligament reconstruction: an in vitro study.

Background: Abnormal tibiofemoral contact stress and aberrant kinematics may influence the progression of osteoarthritis in the anterior cruciate ligament (ACL)-deficient and the ACL-reconstructed knee. However, relationships between contact stress and kinematics after ACL reconstruction are poorly understood. Therefore, we posed the following research questions: (1) How do ACL deficiency and reconstruction affect the kinematics of and contact stress in the tibiofemoral joint? (2) What kinematic differences are associated with abnormal contact stress after ACL reconstruction?

Hypothesis: Center-center ACL reconstruction will not restore knee kinematics and contact stress.

YY1 and a unique DNA repeat element regulates the transcription of mouse CS1 (CD319, SLAMF7) gene.

CS1 (CD319, CRACC, SLAMF7, novel Ly9) activates NK cell-mediated cytotoxicity and proliferation of B lymphocytes during immune responses. The expression of CS1 is up regulated on B cells in multiple myeloma and systemic lupus erythematosus. In this study we describe the transcriptional regulation of mouse CS1 (mCS1) gene.