CX3CR1 deficiency-induced TIL tumor restriction as a novel addition for CAR-T design in solid malignancies.

Advances in the understanding of the tumor microenvironment have led to development of immunotherapeutic strategies, such as chimeric antigen receptor T cells (CAR-Ts). However, despite success in blood malignancies, CAR-T therapies in solid tumors have been hampered by their restricted infiltration. Here, we used our understanding of early cytotoxic lymphocyte infiltration of human lymphocytes in solid tumors to investigate the receptors in normal, adjacent, and tumor tissues of primary non-small-cell lung cancer specimens.

Clinicopathologic characteristics, genetic features, and treatment options for acute lymphoblastic leukemia with JAK2 rearrangement-A 10-case study and literature review.

JAK2 rearrangement (JAK2-R) in acute lymphoblastic leukemia (ALL) is rare and often categorized as B-ALL with BCR::ABL1-like features based on the World Health Organization classification. We report 10 patients with JAK2-R ALL, 9 males and 1 female, with a median age 40.5 years.

Oxidized Mitochondrial DNA Engages TLR9 to Activate the NLRP3 Inflammasome in Myelodysplastic Syndromes.

Myelodysplastic Syndromes (MDSs) are bone marrow (BM) failure malignancies characterized by constitutive innate immune activation, including NLRP3 inflammasome driven pyroptotic cell death. We recently reported that the danger-associated molecular pattern (DAMP) oxidized mitochondrial DNA (ox-mtDNA) is diagnostically increased in MDS plasma although the functional consequences remain poorly defined. We hypothesized that ox-mtDNA is released into the cytosol, upon NLRP3 inflammasome pyroptotic lysis, where it propagates and further enhances the inflammatory cell death feed-forward loop onto healthy tissues.

Dermatologic Events Associated with the Anti-CCR4 Antibody Mogamulizumab: Characterization and Management.

The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event.

Oxidized mitochondrial DNA released after inflammasome activation is a disease biomarker for myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem cell malignancies that can phenotypically resemble other hematologic disorders. Thus, tools that may add to current diagnostic practices could aid in disease discrimination. Constitutive innate immune activation is a pathogenetic driver of ineffective hematopoiesis in MDS through Nod-like receptor protein 3 (NLRP3)-inflammasome-induced pyroptotic cell death.

The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells.

The in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events.

S100A9-induced overexpression of PD-1/PD-L1 contributes to ineffective hematopoiesis in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death of hematopoietic stem and progenitor cells (HSPCs). The PD-1/PD-L1 immune checkpoint impairs immune responses by inducing T-cell exhaustion and apoptosis, but its role in MDS is uncharacterized.

Emerging role of BCR signaling inhibitors in immunomodulation of chronic lymphocytic leukemia.

Approved therapies that target the B-cell receptor (BCR) signaling pathway, such as ibrutinib and idelalisib, are known to show activity in chronic lymphocytic leukemia (CLL) via their direct effects on crucial survival pathways in malignant B cells. However, these therapies also have effects on T cells in CLL by mediating toxicity and possibly controlling disease. By focusing on the effects of BCR signaling inhibitors on the T-cell compartment, we may gain new insights into the comprehensive biological outcomes of systemic treatment to further understand mechanisms of drug efficacy, predict the toxicity or adverse events, and identify novel combinatorial therapies.

Cardiovascular Complications of Targeted Therapies for Chronic Myeloid Leukemia.

The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib.

Anti-VEGF-Induced Hypertension: a Review of Pathophysiology and Treatment Options.

Abnormal intracellular signaling has been implicated in the development of many different types of cancer. Therapies targeting these abnormal pathways have revolutionized the treatment of many malignancies leading to significantly improved outcomes and survival. Despite these advances, cardiovascular toxicity is a frequently reported complication.

A Simple and Efficient Method for Preparing Cell Slides and Staining without Using Cytocentrifuge and Cytoclips.

Cell staining is a necessary and useful technique for visualizing cell morphology and structure under a microscope. This technique has been used in many areas such as cytology, hematology, oncology, histology, virology, serology, microbiology, cell biology, and immunochemistry. One of the key pieces of equipment for preparing a slide for cell staining is cytology centrifuge (cytocentrifuge) such as cytospin.

Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.

Bruton's Tyrosine Kinase (BTK) and IL-2 Inducible T-cell Kinase (ITK) are enzymes responsible for the phosphorylation and activation of downstream effectors in the B-cell receptor (BCR) signaling and T cell receptor (TCR) signaling pathways, respectively. Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function. CD4 T cells and B cells are essential for the induction of chronic graft-versus-host disease (cGVHD).

Cognitive manifestations of drinking-smoking associations: preliminary findings with a cross-primed Stroop task.

Background: Despite tremendous growth in research examining the role of cognitive bias in addictive behaviors, scant consideration has been paid to the close association between smoking and drinking behavior. This study sought to determine whether an association between smoking and drinking could be observed at an implicit level using a novel cognitive bias task, as well as characterize the relationship between performance on this task and clinically relevant variables (i.e.

Evaluation of the functional assessment of cancer therapy cognitive scale with hematopoietic stem cell transplant patients.

The current study evaluated a newly developed self-report measure of cognitive complaints with cancer patients, the Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog). Six or 12 months following hematopoietic stem cell transplantation, participants completed a psychosocial assessment that included the FACT-Cog and a neuropsychological assessment. Using a criterion of two or more times a week, an average of 12 of a total of 50 items were endorsed as complaints on the FACT-Cog.

Large granular lymphocyte leukemia.

Clonal disorders of large granular lymphocytes (LGLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells (CD3+) or natural killer (NK) cells (CD3-). Both subtypes, T-cell and NK-cell LGL leukemia, can manifest as indolent or aggressive disorders. The majority of patients with T-cell LGL leukemia have a clinically indolent course with a median survival time >10 years.

Investigation of the safety and accuracy of intraoperative gamma probe directed biopsy of bone scan detected rib abnormalities in prostatic adenocarcinoma.

Purpose: We evaluated the technique of intraoperative gamma probe directed rib biopsy in patients with suspected metastatic prostate adenocarcinoma. This technique can be used to identify accurately the rib in question, reliably obtain sufficient tissue for diagnosis, be performed with minimal patient morbidity and potentially alter the course of therapy.

Materials And Methods: From 1996 to 2001, 8 patients with biopsy proved adenocarcinoma of the prostate and suspicious rib lesions on radionuclide bone scanning underwent open rib biopsy as part of the evaluation for metastatic disease.

Microscopic paraseptal sphenoidotomy approach for pituitary tumors.

Background: Dissection of mucosa from the nasal septum during a transsphenoidal approach may lead to significant morbidity. Endoscopic techniques that obviate this dissection and its complications have been successful for pituitary operations. These techniques, however, are generally not stereoscopic, can add significant costs, and in many instances require additional surgical personnel.

Assessment of toxicity in cooperative oncology clinical trials: the long and short of it.

Cancer therapy is associated with inherent adverse effects and the need for complete, consistent and accurate reporting of toxicity is paramount in multicenter cooperative oncology clinical trials. Accurate toxicity information is essential to weigh the costs and benefits associated with new treatment regimens. A major issue faced by investigators and clinical trial coordinators today is the lack of clear directions regarding what method should be used in toxicity assessment in cooperative oncology clinical trials.

Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor.

The balanced placebo design (BPD) was used to evaluate the independent effects of nicotine dose and smoking-related expectancies on self-reported anxiety, urge to smoke, and withdrawal symptoms. After anxious mood was induced, participants smoked either a de-nicotinized cigarette or one with standard nicotine content. Nicotine dose was crossed with instructions that the cigarette was either de-nicotinized or standard.

Prolonged activation of the mitogen-activated protein kinase pathway is required for macrophage-like differentiation of a human myeloid leukemic cell line.

The role of the mitogen-activated protein kinase (MAPK) signal transduction pathway in the proliferation of mammalian cells has been well established. However, there are relatively few reports concerning cell differentiation being mediated by MAPK. The effect of phorbol 12-myristate 13-acetate (PMA) on cell differentiation and signal transduction in a human myeloid leukemia cell line, TF-1a, was investigated.

Evaluation and management of parastomal hernia in association with continent urinary diversion.

Purpose: We discuss the incidence and diagnosis of parastomal hernias in association with continent urinary reservoirs. We also present a surgical technique appropriate for correction of this complication.

Materials And Methods: We evaluated 21 patients with parastomal hernia after construction of a continent urinary reservoir.