Dose-Specific Intratumoral GM-CSF Modulates Breast Tumor Oxygenation and Antitumor Immunity.

GM-CSF has been employed as an adjuvant to cancer immunotherapy with mixed results based on dosage. We previously showed that GM-CSF regulated tumor angiogenesis by stimulating soluble vascular endothelial growth factor (VEGF) receptor-1 from monocytes/macrophages in a dose-dependent manner that neutralized free VEGF, and intratumoral injections of high-dose GM-CSF ablated blood vessels and worsened hypoxia in orthotopic polyoma middle T Ag (PyMT) triple-negative breast cancer (TNBC). In this study, we assessed both immunoregulatory and oxygen-regulatory components of low-dose versus high-dose GM-CSF to compare effects on tumor oxygen, vasculature, and antitumor immunity.

The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.

Low tissue oxygenation, termed , is a characteristic of solid tumors with negative consequences. Tumor-associated macrophages (TAMs) accumulate in hypoxic tumor regions and correlate with worse outcomes in cancer patients across several tumor types. Thus, the molecular mechanism in which macrophages respond to low oxygen tension has been increasingly investigated in the last decade.

Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer.

Despite modest improvements in survival in recent years, pancreatic adenocarcinoma remains a deadly disease with a 5-year survival rate of only 9%. These poor outcomes are driven by failure of early detection, treatment resistance, and propensity for early metastatic spread. Uncovering innovative therapeutic modalities to target the resistance mechanisms that make pancreatic cancer largely incurable are urgently needed.

Hypoxia-Inducible Factor α Subunits Regulate Tie2-Expressing Macrophages That Influence Tumor Oxygen and Perfusion in Murine Breast Cancer.

Tie2-expressing monocytes/macrophages (TEMs) are a distinct subset of proangiogenic monocytes selectively recruited to tumors in breast cancer. Because of the hypoxic nature of solid tumors, we investigated if oxygen, via hypoxia-inducible transcription factors HIF-1α and HIF-2α, regulates TEM function in the hypoxic tumor microenvironment. We orthotopically implanted PyMT breast tumor cells into the mammary fat pads of syngeneic LysMcre, HIF-1α /LysMcre, or HIF-2α /LysMcre mice and evaluated the tumor TEM population.

Stress-induced Norepinephrine Downregulates CCL2 in Macrophages to Suppress Tumor Growth in a Model of Malignant Melanoma.

Psychological stressors have been implicated in the progression of various tumor types. We investigated a role for stress in tumor immune cell chemotaxis in the B16F10 mouse model of malignant melanoma. We exposed female mice to 6-hour periods of restraint stress (RST) for 7 days, then implanted B16F10 malignant melanoma tumor cells and continued the RST paradigm for 14 additional days.

Hydrolases of the ILR1-like family of Arabidopsis thaliana modulate auxin response by regulating auxin homeostasis in the endoplasmic reticulum.

Amide-linked conjugates of indole-3-acetic acid (IAA) have been identified in most plant species. They function in storage, inactivation or inhibition of the growth regulator auxin. We investigated how the major known endogenous amide-linked IAA conjugates with auxin-like activity act in auxin signaling and what role ILR1-like proteins play in this process in Arabidopsis.

Glucocorticoids in the treatment of children with acute lymphoblastic leukemia and hodgkin's disease: a pilot study on the adverse psychological reactions and possible associations with neurobiological, endocrine, and genetic markers.

Purpose: We did a controlled study to assess adverse psychological reactions (APR) associated with high-dose glucocorticoid therapy and tried to detect somatic correlates for the observed reactions.

Patients And Methods: Our study included 37 patients with acute lymphoblastic leukemia (ALL) and 11 patients with Morbus Hodgkin (MH) disease, who were treated with high-dose glucocorticoid therapy, and 26 control patients with other types of malignancies. APRs were assessed with a standardized measure via parent-report.

Classification of obsessive-compulsive disorder in childhood and adolescence.

Objective: In child and adolescent psychiatry the validation of the diagnosis must be seen in the context of development. Comparing different diagnostic formulations DSM-IV and ICD-10-DCR in a clinical sample of children and adolescents suffering from obsessive-compulsive disorder (OCD) and their validation on external criteria represent such a heuristic approach.

Method: We investigated 61 children seen consecutively in a specialized out-patient clinic for OCD.

Nonlinear dynamics of 3 Hz spike-and-wave discharges recorded during typical absence seizures in children.

One-channel routine recordings of the scalp electroencephalogram (EEG) from unmedicated children strictly classified as unprovoked typical (3 c/s) absence seizures were selected. The dynamics of spike-and-wave discharges (SWD) were then examined by means of autocorrelation, correlation dimension, averaged pointwise dimension and largest Lyapunov exponent. For one EEG signal with pronounced spike-and-wave (SW) patterns, these measures were used complementary to a surrogate data method, a nonlinear (SETAR) modeling approach, and a SW simulation procedure providing five types of SW test signals.

Simultaneous spike detection and topographic classification in pediatric surface EEGs.

In this study, an algorithm is introduced for the automatic detection and simultaneous topographic classification of interictal regional spike activity in pediatric surface EEG records. The algorithm is based on the classification of the topographic distribution of instantaneous power by means of a 'group' trained classifier. The results of automatic spike analysis were compared with the decisions of two experienced electroencephalographers.

High frequency of EEG and MRI brain abnormalities in panic disorder.

The frequency and quality of brain abnormalities in panic disorder (PD) were assessed with magnetic resonance imaging (MRI). The use of electroencephalography (EEG) to detect PD patients with a high probability of morphologic brain abnormalities was also explored. Consecutive PD patients (n = 120) were screened with routine EEG examinations and were divided into the following subgroups on the basis of their EEG findings: patients with non-epileptic EEG abnormalities (EEG-A group, n = 28), matched patients with normal EEG results (EEG-N group, n = 28) and matched healthy controls (n = 28).

Is there a pathophysiological and therapeutic link between panic disorder and epilepsy?

Relations between panic disorder (PD) and epilepsy (E) have repeatedly been discussed. Three patients with juvenile E who had been free of seizures under anticonvulsant medication for many years and developed PD are presented. Increasing anticonvulsant medication resulted in complete and stable remission of PD.

EEG-brain mapping in schizophrenics with predominantly positive and negative symptoms. Comparative studies with remoxipride/haloperidol.

EEG brain maps obtained in 48 drug-free hospitalized schizophrenics diagnosed according to DSMIII demonstrated significant differences as compared with normal controls characterized by a decrease of alpha-1 activity, increase of beta activity and acceleration of the centroid. These findings suggest a state of sustained hyperarousal in schizophrenia. While the patients with negative schizophrenia showed a bi-temporal and frontal augmentation of delta/theta activity, patients with florid symptomatology exhibited just the opposite findings.

Smooth pursuit eye movements in schizophrenia: influences of neuroleptic treatment and the question of specificity.

The authors investigated smooth pursuit eye movements (SPEMs) in 66 schizophrenic and 40 major affective patients and 39 healthy controls. The results showed significant differences of both patient groups as compared to the controls. Schizophrenics with neuroleptic treatment in the preceding 2 years were significantly more disturbed than the controls, the affective patients and the untreated schizophrenics.