Social and nonsocial environmental loss have differential effects on ventral hippocampus-dependent behavior and inhibitory synaptic markers in adult male mice.

In humans, psychological loss, whether social or nonsocial, can lead to clinical depression, anxiety disorders, and social memory impairments. Researchers have modeled combined social and nonsocial loss in rodents by transitioning them from social, enriched environments (EE) to individual housing, affecting behaviors related to avoidance, stress coping, and cognitive function. However, it remains unclear if these effects are driven by social or nonsocial loss.

Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors.

Although the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple tumors at presentation in individuals with EGFR-mutant lung cancer who lack known environmental exposures remains unexplained. In the present study, we identified ten patients with early stage, resectable, non-small cell lung cancer who presented with multiple, anatomically distinct, EGFR-mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole-exome sequencing (WES) and hypermutable poly(guanine) (poly(G)) repeat genotyping as orthogonal methods for lineage tracing.

Adult-born granule cells modulate CA2 network activity during retrieval of developmental memories of the mother.

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but it remains unknown how this circuit affects behavioral function. Here, we show that abGC input to the CA2 of adult mice is involved in the retrieval of remote developmental memories of the mother. Ablation of abGCs impaired the ability to discriminate between a caregiving mother and a novel mother, and this ability returned after abGCs were regenerated.

Developmental and adult stress: effects of steroids and neurosteroids.

In humans, exposure to early life adversity has profound implications for susceptibility to developing neuropsychiatric disorders later in life. Studies in rodents have shown that stress experienced during early postnatal life can have lasting effects on brain development. Glucocorticoids and sex steroids are produced in endocrine glands and the brain from cholesterol; these molecules bind to nuclear and membrane-associated steroid receptors.

Germline mutations and developmental mosaicism underlying -mutant lung cancer.

While the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple primary tumors in individuals with -mutant lung cancer who lack known environmental exposures remains unexplained. We identified ten patients with early-stage, resectable non-small cell lung cancer who presented with multiple anatomically distinct -mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole exome sequencing (WES) and hypermutable poly-guanine (poly-G) repeat genotyping, as orthogonal methods for lineage tracing.

Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice.

Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1).

Three new species of the Merodon ruficornis group (Diptera: Syrphidae) discovered at the edge of its range.

Further revision of material from the Merodon ruficornis group (Diptera: Syrphidae) revealed three new species, M. acutus Vuji et Radenkovi sp. nov.

PSMA ADC monotherapy in patients with progressive metastatic castration-resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open-label single-arm phase 2 study.

Background: Prostate-specific membrane antigen (PSMA) is a well-established therapeutic and diagnostic target overexpressed in both primary and metastatic prostate cancers. PSMA antibody-drug conjugate (PSMA ADC) is a fully human immunoglobulin G1 anti-PSMA monoclonal antibody conjugated to monomethylauristatin E, which binds to PSMA-positive cells and induces cytotoxicity. In a phase 1 study, PSMA ADC was well tolerated and demonstrated activity as measured by reductions in serum prostate-specific antigen (PSA) and circulating tumor cells (CTCs).

Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP).

Background: This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.

Methods: Patients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data.

Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with FOLFOX and Bevacizumab for First-Line Metastatic Colorectal Cancer.

Lessons Learned: These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents.

Background: EGFL7 (epidermal growth factor-like domain 7) is a tumor-enriched vascular extracellular matrix protein that supports endothelial cell survival.

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer.

Methods: We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America.

Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study.

Background: Previous results suggest that docetaxel plus cyclophosphamide improves disease-free survival (DFS) and overall survival compared with doxorubicin plus cyclophosphamide in early stage breast cancer. We assessed the addition of 1 year of trastuzumab to a non-anthracycline regimen, docetaxel plus cyclophosphamide, in patients with HER2-amplified early stage breast cancer and examined whether this regimen was equally effective in patients with TOP2A-amplified and TOP2A-non-amplified disease.

Methods: This was an open-label, single-group, phase 2 study.

A randomized phase II trial of vismodegib versus placebo with FOLFOX or FOLFIRI and bevacizumab in patients with previously untreated metastatic colorectal cancer.

Purpose: Vismodegib, a Hedgehog pathway inhibitor, has preclinical activity in colorectal cancer (CRC) models. This trial assessed the efficacy, safety, and pharmacokinetics of adding vismodegib to first-line treatment for metastatic CRC (mCRC).

Experimental Design: Patients were randomized to receive vismodegib (150 mg/day orally) or placebo, in combination with FOLFOX or FOLFIRI chemotherapy plus bevacizumab (5 mg/kg) every 2 weeks until disease progression or intolerable toxicity.

Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.

Purpose: Safety and efficacy of tremelimumab (CP-675,206), a fully human anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody, were assessed in patients with treatment-refractory colorectal cancer.

Patients And Methods: A single-arm, multicenter, phase II trial was conducted in patients with Eastern Cooperative Oncology Group performance status View Article and Find Full Text PDF

A phase 2 study of a fixed combination of uracil and ftorafur and leucovorin given orally in a twice-daily regimen to treat patients with recurrent metastatic breast cancer.

Background: UFT, a combination of uracil and ftorafur, was developed to combine the cytotoxic effects of 5-fluorouracil (5-FU) with convenient oral dosing. Leucovorin is combined with UFT to further potentiate the effect of 5-FU on tumor cells. Orally administered UFT and leucovorin provide higher peak plasma concentrations of 5-FU and prolonged therapeutic 5-FU concentrations compared with continuous infusion of 5-FU.

Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR.

Somatic activating mutations in EGFR identify a subset of non-small cell lung cancer that respond to tyrosine kinase inhibitors. Acquisition of drug resistance is linked to a specific secondary somatic mutation, EGFR T790M. Here we describe a family with multiple cases of non-small cell lung cancer associated with germline transmission of this mutation.

A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim.

HTLV-I-associated myelopathy and polymyositis in a US native.

A patient who had always lived in the United States had an HTLV-I infection and a chronic myelopathy clinically mimicking amyotrophic lateral sclerosis. Needle EMG and nerve conduction studies were consistent with anterior horn cell disease but muscle biopsy showed denervation and an inflammatory myopathy. Serum HTLV-I antibody tests were positive and HTLV-I DNA was present in peripheral leukocytes.

Neuroendocrine differentiation in prostatic carcinomas. A retrospective autopsy study.

Neuroendocrine differentiation in prostatic neoplasms has in the past been considered extremely uncommon. The histologic neuroendocrine patterns reported previously vary from small cell to carcinoidlike to mixed adenocarcinoma--small cell or carcinoid. The majority of the tumors reported are of the mixed variety.