US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816.

Purpose: Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma.

Patients And Methods: The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2.

Sex-Specific Associations Between Coronary Artery Plaque Extent and Risk of Major Adverse Cardiovascular Events: The CONFIRM Long-Term Registry.

Objectives: The purpose of this study was to examine sex-specific associations, if any, between per-vessel coronary artery disease (CAD) extent and the risk of major adverse cardiovascular events (MACE) over a 5-year study duration.

Background: The presence and extent of CAD diagnosed by coronary computed tomography angiography (CTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of sex on these findings.

Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease: Prevalence and Association with PKD2 Gene Mutations.

Purpose To define the magnetic resonance (MR) imaging prevalence of pancreatic cysts in a cohort of patients with autosomal dominant polycystic kidney disease (ADPKD) compared with a control group without ADPKD that was matched for age, sex, and renal function. Materials and Methods In this HIPAA-compliant, institutional review board-approved study, all patients with ADPKD provided informed consent; for control subjects, informed consent was waived. Patients with ADPKD (n = 110) with mutations identified in PKD1 or PKD2 and control subjects without ADPKD or known pancreatic disease (n = 110) who were matched for age, sex, estimated glomerular filtration rate, and date of MR imaging examination were evaluated for pancreatic cysts by using axial and coronal single-shot fast spin-echo T2-weighted images obtained at 1.

CHOP Chemotherapy Followed by Tositumomab and Iodine-131 Tositumomab for Previously Untreated Diffuse Large B-cell Lymphoma.

The efficacy and safety of tositumomab/iodine-131 tositumomab (TST/I-131 TST) were evaluated in diffuse large B-cell lymphoma patients who responded to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Fifteen patients (median age, 52 years) received dosimetric and therapeutic doses of TST/I-131 TST. The most common Grade 3/4 hematologic adverse events were decreased absolute neutrophil count (47%), white blood cell count (40%), platelet count (27%), and hemoglobin (20%).

Organoid culture systems for prostate epithelial and cancer tissue.

This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumor. We explain how to establish these cultures in the fully defined serum-free conditioned medium that is required to sustain organoid growth.

Myriad Functions of Stanniocalcin-1 (STC1) Cover Multiple Therapeutic Targets in the Complicated Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF).

Idiopathic pulmonary fibrosis (IPF) is an intractable disease for which the pathological findings are characterized by temporal and spatial heterogeneity. The pathogenesis is composed of myriad factors, including repetitive injuries to epithelial cells, alterations in immunity, the formation of vascular leakage and coagulation, abnormal wound healing, fibrogenesis, and collagen accumulation. Therefore, the molecular target drugs that are used or attempted for treatment or clinical trials may not cover the myriad therapeutic targets of IPF.

Anxiety Disorders Among Children and Adolescents.

Anxiety disorders represent the most common psychiatric illnesses affecting children and adolescents. Youths who suffer from anxiety disorders typically experience impairment in social, family, and educational domains of functioning. Despite the prevalence of youth anxiety disorders, identifying anxiety as the underlying cause can be a challenge.

Primary Desmoplastic Melanoma of the Penis.

Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis.

Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma.

Background: Mantle-cell lymphoma is generally incurable. Initial treatment is not standardized but usually includes cytotoxic chemotherapy. Lenalidomide, an immunomodulatory compound, and rituximab, an anti-CD20 antibody, are active in patients with recurrent mantle-cell lymphoma.

Carbon monoxide in the treatment of sepsis.

Carbon monoxide (CO), a low-molecular-weight gas, is endogenously produced in the body as a product of heme degradation catalyzed by heme oxygenase (HO) enzymes. As the beneficial roles of HO system have been elucidated in vitro and in vivo, CO itself has also been reported as a potent cytoprotective molecule. Whereas CO represents a toxic inhalation hazard at high concentration, low-dose exogenous CO treatment (~250-500 parts per million) demonstrates protective functions including but not limited to the anti-inflammatory and antiapoptotic effects in preclinical models of human diseases.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force.

Objectives: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD).

Methods: This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches.

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance).

Purpose: Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies.

Patients And Methods: The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m(2) weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR.

Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study.

Background: Hypomethylating agents are used to treat cancers driven by aberrant DNA methylation, but their short half-life might limit their activity, particularly in patients with less proliferative diseases. Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. We aimed to assess the safety and clinical activity of subcutaneously given guadecitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex.

Unlabelled: mTOR serves as a central regulator of cell growth and metabolism by forming two distinct complexes, mTORC1 and mTORC2. Although mechanisms of mTORC1 activation by growth factors and amino acids have been extensively studied, the upstream regulatory mechanisms leading to mTORC2 activation remain largely elusive. Here, we report that the pleckstrin homology (PH) domain of SIN1, an essential and unique component of mTORC2, interacts with the mTOR kinase domain to suppress mTOR activity.

Impaired oxidative phosphorylation regulates necroptosis in human lung epithelial cells.

Cellular metabolism can impact cell life or death outcomes. While metabolic dysfunction has been linked to cell death, the mechanisms by which metabolic dysfunction regulates the cell death mode called necroptosis remain unclear. Our study demonstrates that mitochondrial oxidative phosphorylation (OXPHOS) activates programmed necrotic cell death (necroptosis) in human lung epithelial cells.

mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation.

The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. Although glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation.

Short-term Exposure to Ambient Fine Particulate Matter Increases Hospitalizations and Mortality in COPD: A Systematic Review and Meta-analysis.

Background: Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and COPD hospitalizations and mortality in cities worldwide.

Methods: Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary ORs and 95% CIs were calculated to evaluate the relationship between short-term exposure to PM with aerodynamic diameters ≤ 2.

Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function.

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.

The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases.

Significance: Mitochondria, vital cellular power plants to generate energy, are involved in immune responses. Mitochondrial damage-associated molecular patterns (DAMPs) are molecules that are released from mitochondria to extracellular space during cell death and include not only proteins but also DNA or lipids. Mitochondrial DAMPs induce inflammatory responses and are critically involved in the pathogenesis of various diseases.

The regulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase by autophagy in low-glycolytic hepatocellular carcinoma cells.

The glycolytic phenotype is a dominant metabolic phenomenon in cancer and is reflected in becoming aggressive. Certain hepatocellular carcinoma lack increased glycolysis and prefer to uptake acetate than glucose for metabolism. Autophagy plays a role in preserving energies and nutrients when there is limited external nutrient supply and maintains glucose level of blood though supporting gluconeogenesis in the liver.

Rating scales measuring the severity of psychotic depression.

Objective: Unipolar psychotic depression (PD) is a severe and debilitating syndrome, which requires intensive monitoring. The objective of this study was to provide an overview of the rating scales used to assess illness severity in PD.

Method: Selective review of publications reporting results on non-self-rated, symptom-based rating scales utilized to measure symptom severity in PD.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

Rationale: A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial.

Functional characterization of BC039389-GATM and KLK4-KRSP1 chimeric read-through transcripts which are up-regulated in renal cell cancer.

Background: Chimeric read-through RNAs are transcripts originating from two directly adjacent genes (<10 kb) on the same DNA strand. Although they are found in next-generation whole transcriptome sequencing (RNA-Seq) data on a regular basis, investigating them further has usually been refrained from. Therefore, their expression patterns or functions in general, and in oncogenesis in particular, are poorly understood.

Organoid development in cancer genome discovery.

The tumor response to most therapeutic agents in cancer is highly unpredictable. Cancer models which can adequately represent tumor heterogeneity and predict in vivo drug sensitivity are intense areas of investigation. Cancer cell lines and patient-derived xenograft models are the most frequently used models in cancer research and anticancer drug screening.