Diagnostic utility of phosphorylated signal transducer and activator of transcription 5 immunostaining in the diagnosis of mammary analogue secretory carcinoma of the salivary gland: A comparative study of salivary gland cancers.

Background: Mammary analogue secretory carcinoma (MASC) with an ETS variant gene 6 (ETV6)-neurotrophic tyrosine kinase receptor type 3 (NTRK3) translocation is a newly described type of salivary gland cancer. It is known that overexpression of signal transducer and activator of transcription 5a (STAT5a) occurs in secretory carcinoma of the breast and MASC, and STAT5a expression may be related to the ETV6-NTRK3 translocation. It was hypothesized that phosphorylated signal transducer and activator of transcription 5 (p-STAT5) might be specifically expressed in MASC of the salivary gland.

Epidermal growth factor receptor mutation status in cell-free DNA supernatant of bronchial washings and brushings.

Background: The aim of the current study was to examine whether it would be possible to detect epidermal growth factor receptor (EGFR) mutations in cytology cell-free DNA (ccfDNA) from the supernatant fluids of bronchial cytology samples.

Methods: This study investigated cell damage via immunostaining with a cleaved caspase 3 antibody and the quantity of cell-free DNA in supernatant fluid from 2 cancer cell lines, and the EGFR mutation status was evaluated via polymerase chain reaction (PCR) analysis. EGFR mutations were also evaluated via PCR analysis in 74 clinical samples of ccfDNA from bronchial washing samples with physiological saline or from bronchial brushing liquid-based cytology samples with CytoRich Red.

INSECT PHYLOGENOMICS. Response to Comment on "Phylogenomics resolves the timing and pattern of insect evolution".

Tong et al. comment on the accuracy of the dating analysis presented in our work on the phylogeny of insects and provide a reanalysis of our data. They replace log-normal priors with uniform priors and add a "roachoid" fossil as a calibration point.

Wolbachia in butterflies and moths: geographic structure in infection frequency.

Introduction: Butterflies and moths (Lepidoptera) constitute one of the most diverse insect orders, and play an important role in ecosystem function. However, little is known in terms of their bacterial communities. Wolbachia, perhaps the most common and widespread intracellular bacterium on Earth, can manipulate the physiology and reproduction of its hosts, and is transmitted vertically from mother to offspring, or sometimes horizontally between species.

A framework to assess evolutionary responses to anthropogenic light and sound.

Human activities have caused a near-ubiquitous and evolutionarily-unprecedented increase in environmental sound levels and artificial night lighting. These stimuli reorganize communities by interfering with species-specific perception of time-cues, habitat features, and auditory and visual signals. Rapid evolutionary changes could occur in response to light and noise, given their magnitude, geographical extent, and degree to which they represent unprecedented environmental conditions.

Comprehensive analysis of sphingosine-1-phosphate receptor mutants during zebrafish embryogenesis.

The lipid mediator sphingosine-1-phosphate (S1P) regulates various physiological and pathological phenomena such as angiogenesis and oncogenesis. Secreted S1P associates with the G-protein-coupled S1P receptors (S1PRs), leading to the activation of downstream signaling molecules. In mammals, five S1prs have been identified and the genetic disruption of a single S1pr1 gene causes vascular defects.

Role of Caribbean Islands in the diversification and biogeography of Neotropical Heraclides swallowtails.

Numerous hypotheses on the evolution of Neotropical biodiversity have stimulated research to provide a better understanding of diversity dynamics and distribution patterns of the region. However, few studies integrate molecular and morphological data with complete sampling of a Neotropical group, and so there has been little synthesis of the multiple processes governing biodiversity through space and time. Here, a total-evidence phylogenetic approach is used to reconstruct the evolutionary history of the butterfly subgenus Heraclides.

Induction of PD-L1 Expression by the EML4-ALK Oncoprotein and Downstream Signaling Pathways in Non-Small Cell Lung Cancer.

Purpose: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in a subset of patients with non-small cell lung cancer (NSCLC). We have now examined PD-L1 expression and its regulation in NSCLC positive for the EML4-ALK fusion gene.

Experimental Design: The expression of PD-L1 at the protein and mRNA levels in NSCLC cell lines was examined by flow cytometry and by reverse transcription and real-time PCR analysis, respectively.

Efficient Multiple Genome Modifications Induced by the crRNAs, tracrRNA and Cas9 Protein Complex in Zebrafish.

The type II clustered regularly interspaced short palindromic repeats (CRISPR) associated with Cas9 endonuclease (CRISPR/Cas9) has become a powerful genetic tool for understanding the function of a gene of interest. In zebrafish, the injection of Cas9 mRNA and guide-RNA (gRNA), which are prepared using an in vitro transcription system, efficiently induce DNA double-strand breaks (DSBs) at the targeted genomic locus. Because gRNA was originally constructed by fusing two short RNAs CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), we examined the effect of synthetic crRNAs and tracrRNA with Cas9 mRNA or Cas9 protein on the genome editing activity.

Reversible methotrexate-associated lymphoma of the liver in rheumatoid arthritis: a unique case of primary hepatic lymphoma.

Primary hepatic lymphoma (PHL) is an extremely rare disease, frequently associated with viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immune deficiency virus (HIV). On the other hand, an increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with immunosuppressive drugs such as methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of the immunodeficiency-associated LPDs.

Body size affects the evolution of eyespots in caterpillars.

Many caterpillars have conspicuous eye-like markings, called eyespots. Despite recent work demonstrating the efficacy of eyespots in deterring predator attack, a fundamental question remains: Given their protective benefits, why have eyespots not evolved in more caterpillars? Using a phylogenetically controlled analysis of hawkmoth caterpillars, we show that eyespots are associated with large body size. This relationship could arise because (i) large prey are innately conspicuous; (ii) large prey are more profitable, and thus face stronger selection to evolve such defenses; and/or (iii) eyespots are more effective on large-bodied prey.

Tempo and mode of antibat ultrasound production and sonar jamming in the diverse hawkmoth radiation.

The bat-moth arms race has existed for over 60 million y, with moths evolving ultrasonically sensitive ears and ultrasound-producing organs to combat bat predation. The evolution of these defenses has never been thoroughly examined because of limitations in simultaneously conducting behavioral and phylogenetic analyses across an entire group. Hawkmoths include >1,500 species worldwide, some of which produce ultrasound using genital stridulatory structures.

Neoplastic spindle cells are an independent prognostic factor in pancreatic cancer.

Objective: Several reports showed that neoplastic spindle cells (NSCs) may be strongly involved in the invasion, metastasis, and poor prognosis, as well as in epithelial-mesenchymal transition (EMT). It has not yet been investigated that NSCs relate to the recurrence and prognosis in various cancers. Furthermore, NSCs participate in EMT in pancreatic cancer (PC) too.

Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study.

Objective: Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR.

Maternal and Zygotic Sphingosine Kinase 2 Are Indispensable for Cardiac Development in Zebrafish.

Sphingosine 1-phosphate (S1P) is synthesized from sphingosine by sphingosine kinases (SPHK1 and SPHK2) in invertebrates and vertebrates, whereas specific receptors for S1P (S1PRs) selectively appear in vertebrates, suggesting that S1P acquires novel functions in vertebrates. Because the developmental functions of SPHK1 and SPHK2 remain obscure in vertebrates, we generated sphk1 or sphk2 gene-disrupted zebrafish by introducing premature stop codons in their coding regions using transcription activator-like effector nucleases. Both zygotic sphk1 and sphk2 zebrafish mutants exhibited no obvious developmental defects and grew to adults.

Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas: a comparative study between small biopsy and excision samples.

Introduction: The standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has been reported as a potential method in screening for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinomas (NSCLC), whereas several authors have reported a discordance between FISH and IHC results. We investigated the heterogeneity of ALK gene rearrangement in excision specimens by FISH and also examined whether the FISH score of ALK gene rearrangement corresponded in excision and biopsy samples from the same patient.

Precise in-frame integration of exogenous DNA mediated by CRISPR/Cas9 system in zebrafish.

The CRISPR/Cas9 system provides a powerful tool for genome editing in various model organisms, including zebrafish. The establishment of targeted gene-disrupted zebrafish (knockouts) is readily achieved by CRISPR/Cas9-mediated genome modification. Recently, exogenous DNA integration into the zebrafish genome via homology-independent DNA repair was reported, but this integration contained various mutations at the junctions of genomic and integrated DNA.

Moth tails divert bat attack: evolution of acoustic deflection.

Adaptations to divert the attacks of visually guided predators have evolved repeatedly in animals. Using high-speed infrared videography, we show that luna moths (Actias luna) generate an acoustic diversion with spinning hindwing tails to deflect echolocating bat attacks away from their body and toward these nonessential appendages. We pit luna moths against big brown bats (Eptesicus fuscus) and demonstrate a survival advantage of ∼ 47% for moths with tails versus those that had their tails removed.

Lung adenocarcinoma metastasis to the male breast: a case report.

We report the case of a 60-year-old male patient who was diagnosed with metastasis from primary lung cancer to the breast. The patient presented with a mass in the right breast. Mammography, ultrasound, and magnetic-resonance imaging each suggested primary breast cancer.

Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer.

Background: Programmed cell death 1 receptor-ligand interaction is a major pathway often hijacked by tumors to suppress immune control. The aim of this retrospective study was to investigate the prevalence and prognostic roles of programmed cell death -ligand 1 (PD-L1) expression in small cell lung cancer (SCLC).

Methods: The expression of PD-L1 was evaluated by immunohistochemical analysis in 102 specimens of SCLC.

Phylogenomics resolves the timing and pattern of insect evolution.

Insects are the most speciose group of animals, but the phylogenetic relationships of many major lineages remain unresolved. We inferred the phylogeny of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide and amino acid sequences, with site-specific nucleotide or domain-specific amino acid substitution models, produced statistically robust and congruent results resolving previously controversial phylogenetic relations hips.

Phase II study of personalized peptide vaccination for previously treated advanced colorectal cancer.

The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events.

Feasibility study of personalized peptide vaccination for advanced non-small cell lung cancer patients who failed two or more treatment regimens.

The prognosis of non-small cell lung cancer (NSCLC) patients who failed two or more treatment regimens remains very poor. We conducted a phase II study to explore the feasibility of personalized peptide vaccination (PPV), in which peptides are selected and administered based on the pre-existing host immunity before vaccination, as a third or more line treatment in advanced NSCLC patients who failed two or more regimens. Among 57 patients enrolled, 23 or 16 patients received PPV with chemotherapy or targeted therapy, respectively, whereas 18 patients received PPV alone.

Evaluation of immunohistochemistry using two different antibodies and procedures for primary lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangement.

Rearrangements of anaplastic lymphoma kinase (ALK) have been recently identified in non-small cell lung carcinomas. Previous studies have revealed characteristic features, including adenocarcinoma histology and mucin production, in ALK-positive lung carcinoma. The present study evaluated immunohistochemistry (IHC) in ALK-positive lung carcinoma using two different antibodies, clone 5A4 and D5F3, and compared the results.