Serial killers

Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells...

Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, pleasant aromas, and fresh, clean air. In Japan, since 2004, serial studies have been conducted to investigate the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. My research team has established a new medical science called Forest Medicine. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which studies the effects of forest environments (Forest bathing/Shinrin-yoku) on human health...

BACKGROUND: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. METHODS: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation...

Cytotoxic CD8 T cells (CTLs) are classically described as the "serial killers" of the immune system, where they play a pivotal role in protective immunity against a wide spectrum of pathogens and tumors. Ironically, they are critical drivers of transplant rejection and autoimmune diseases, a scenario very similar to the famous novel " The strange case of Dr. Jekyll and Mr. Hyde". Until recently, it has not been well-appreciated whether CTLs can also acquire non-cytotoxic functions in health and disease. Several investigations into this question revealed their non-cytotoxic functions through interactions with various immune and non-immune cells...

BACKGROUND: CD38 is a pleiotropic cell surface molecule with a short cytoplasmic tail. This molecule is highly expressed by multiple myeloma (MM) cells, and it was chosen as the target of therapeutic monoclonal antibodies, such as daratumumab (Dara). This work aims at investigating how Dara interacts with target and immune cells and what effects are induced on natural killer (NK) cells and myeloid-derived suppressor cells (MDSCs). MATERIALS AND METHODS: Experiments were conducted on MM-derived cell lines stabilized in our laboratory and fresh human myeloma cells...

The topic of sexual homicide encompasses various categories of both offender and victim and much research has shown that there are different typologies of sexual homicide offender (SHO). The aim of this study was to review the current literature regarding sexual homicides, with a focus on those SHOs that targeted children. Studies were selected for review based on the samples utilized. Studies that used a mixed sample of sexual homicide, for example, serial/non-serial, adult/child victim, stranger/non-stranger relationship were included, as well as those that exclusively investigated sexual killers of children...

The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PRs) - S1P1-5 . S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads to side effects. In this article, we describe a 2...

Most common methods of cellular analysis employ the top-down approach (investigating proteomics or genomics directly), thereby destroying the cell, which does not allow the possibility of using the same cell to correlate genomics with functional assays. Herein we describe an approach for single-cell tools that serve as a bottom-up approach. Our technology allows functional phenotyping to be conducted by observing the cytotoxicity of cells and then probe the underlying biology. We have developed a droplet microfluidic device capable of trapping droplets in the array and releasing the droplet of interest selectively using microvalves...

Chimeric antigen receptor T (CAR-T) cell immunotherapies have seen success in treating hematological malignancies in recent years; however, the results can be highly variable. Single cell heterogeneity plays a key role in the variable efficacy of CAR-T cell treatments yet is largely unexplored. A major challenge is to understand the killing behavior and phenotype of individual CAR-T cells which are able to serially kill targets. Thus, a platform capable of measuring time-dependent CAR-T cell mediated killing and then isolating single cells for downstream assays would be invaluable in characterizing CAR-T cells...

Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level. Here we describe a system, called BEHAV3D, developed to study the dynamic interactions of immune cells and patient cancer organoids by means of imaging and transcriptomics. We apply BEHAV3D to live-track >150,000 engineered T cells cultured with patient-derived, solid-tumor organoids, identifying a 'super engager' behavioral cluster comprising T cells with potent serial killing capacity...

Despite contemporary media portrayals, violent crime has continued to decrease in recent decades. Consistent with traditional types of violent crime (e.g., homicide), serial homicide has also continued to decrease. Although the methods of investigation for traditional violent crime have been examined thoroughly, research specific to serial homicide is scarce. In a study of 671 serial homicide perpetrators, we examined the timeline of each investigation and identified the methods used by law enforcement to identify, and sometimes apprehend, serial killers...

Serial criminality, although rare, has always aroused the interest of researchers in criminology, psychiatry, psychology, and sociology. We report the case of a patient, suffering from a chronic psychotic disorder, having committed several murders over a period of 9 years, underpinned by a delirium of misidentification of Frigoli syndrome.

Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein-Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA...

OBJECTIVE: To examine the expression of uterine natural killer (uNK) cells and cytotoxic T lymphocytes (CTLs) in endometrial biopsies from reproductive-age women with and without nonstructural abnormal uterine bleeding (AUB) and evaluate the expression of granulysin within these cell populations and potential modulation of matrix metalloproteinase (MMP) expression. DESIGN: Experimental study, retrospective design. SETTING: Academic research laboratory...

Cancer cells acquire immunoediting ability to evade immune surveillance and thus escape eradication. It is widely known that mutant proteins encoded from tumor suppressor TP53 exhibit gain-of-function in cancer cells, thereby promoting progression; however, how mutant p53 contributes to the sheltering of cancer cells from host anticancer immunity remains unclear. Herein, we report that murine p53 missense mutation G242A (corresponding to human G245A) suppresses the activation of host natural killer (NK) cells, thereby enabling breast cancer cells to avoid immune assault...

Serial murder is a specific type of violent crime that falls into the crime category of multicide. According to the nomenclature of the Federal Bureau of Investigation's Violent Crime Classification Manual and Academic Researchers for the Classification of Violent Crimes, most serial killers are adults. However, serial murder is also committed by young people, although to a lesser extent. Young serial killers are a topic of relevance in areas such as psychology, criminology, and the justice system. Given that the study of the variables that could be the basis of such multicide criminality is not conclusive, the need for further research is evident...

NK cell-mediated cytotoxicity is a critical element of our immune system required for protection from microbial infections and cancer. NK cells bind to and eliminate infected or cancerous cells via direct secretion of cytotoxic molecules toward the bound target cells. In this review, we summarize the current understanding of the molecular regulations of NK cell cytotoxicity, focusing on lytic granule development and degranulation processes. NK cells synthesize apoptosis-inducing proteins and package them into specialized organelles known as lytic granules (LGs)...

BACKGROUND: The NK cell line NK-92 and its genetically modified variants are receiving attention as immunotherapies to treat a range of malignancies. However, since NK-92 cells are themselves tumors, they require irradiation prior to transfer and are potentially susceptible to attack by patients' immune systems. Here, we investigated NK-92 cell-mediated serial killing for the effects of gamma-irradiation and ligation of the death receptor Fas (CD95), and NK-92 cell susceptibility to attack by activated primary blood NK cells...

Epigenetic modification is an important process during hematopoietic cell differentiation. Histone deacetylase (HDAC) inhibitors have previously been shown to enhance expansion of umbilical cord blood-derived hematopoietic stem cells (HSCs). However, the effect of HDAC inhibitors on pluripotent stem cells (PSCs) in this context is less understood. For years, investigators have considered PSC-derived natural killer (NK) and T-cell therapies. These "off-the-shelf" cellular therapies are now entering the clinic...

BACKGROUND: We recently conducted Cetuximab-AVElumab-Lung (CAVE-Lung), a proof-of-concept, translational and clinical trial, to evaluate the combination of two IgG1 monoclonal antibodies (mAb): avelumab, an anti-PD-L1 drug, and cetuximab, an anti-epidermal growth factor receptor (EGFR) drug, as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. We have reported clinically relevant anti-tumor activity in 6/16 patients. Clinical benefit was accompanied by Natural Killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC)...