Neuroendocrine differentiation and neuroendocrine morphology as two different patterns in large-cell bronchial carcinomas: outcome after complete resection

BACKGROUND: In 1999, large-cell neuroendocrine carcinoma of the lung was introduced by the World Health Organization (WHO) as a new tumor entity in the group of non-small cell, epithelial tumors, a differentiated classification of neuroendocrine tumors of the lung not existing until this time. Scientific knowledge on prognosis and therapy of these tumors, especially between those with neuroendocrine morphology only and those showing additional expression of neuroendocrine markers, is fragmentary. In this analysis, we studied the clinical behavior and the prognosis of these two rare tumor entities. PATIENTS AND METHODS: The analysis comprises 12 patients of a total of 2053, who underwent thoracotomy for non small-cell lung carcinoma between 1997 and 2005 in the Department of Thoracic Surgery at the University Hospital of Freiburg. Clinical data, pathological examinations as well as complete follow-up were reviewed from large-cell carcinoma with neuroendocrine morphology only (n=4) and from large-cell carcinoma expressing neuroendocrine markers (n=8). RESULTS: The median survival of patients with neuroendocrine morphology was 30 months (11–96 months). In the patient group showing the expression of neuroendocrine markers, the median survival time was 20 months (2–26 months). Tumor recurrences occurred in the group with neuroendocrine morphology, without exception, in the form of distant metastases and in the group with neuroendocrine markers as intrapulmonary metastases. CONCLUSION: Large-cell neuroendocrine carcinomas of the lung show aggressive behavior with a poor prognosis. Expression of neuroendocrine markers markedly reduce tumor-free interval as well as survival and might influence the site of metastases

A fully planar solar pumped laser based on a luminescent solar collector

A solar-pumped laser (SPL) that converts sunlight directly into a coherent and intense laser beam generally requires a large concentrating lens and precise solar tracking, thereby limiting its potential utility. Here, we demonstrate a fully-planar SPL without a lens or solar tracking. A Nd3+-doped silica fiber is coiled into a cylindrical chamber filled with a sensitizer solution, which acts as a luminescent solar collector. The body of the chamber is highly reflective while the top window is a dichroic mirror that transmits incoming sunlight and traps the fluorescence emitted by the sensitizer. The laser-oscillation threshold was reached at a natural sunlight illumination of 60% on the top window. Calculations indicated that a solar-to-laser power-conversion efficiency could eventually reach 8%. Such an SPL has potential applications in long-term renewable-energy storage or decentralised power supplies for electric vehicles and Internet-of-Things devices

Structural Observation of the Primary Isomerization in Vision with Femtosecond-Stimulated Raman

the substrate surface (27) with DOS of polymers could occur, or there could be charge transfer (28) based on the interaction between the polymers and the I-Au(111). These electronic interactions between the polymers and the surface might reduce the HOMO-LUMO gaps compared with those in solution. Chem. Soc. 124, 11862 (2002). 11. H. Sakaguchi, H. Matsumura, H. Gong, Nat. Mater. 3, 551 (2004 Science 271, 1705Science 271, (1996. Adv. Mater. 4, 282 (1992 The primary event that initiates vision is the light-induced 11-cis to all-trans isomerization of retinal in the visual pigment rhodopsin. Despite decades of study with the traditional tools of chemical reaction dynamics, both the timing and nature of the atomic motions that lead to photoproduct production remain unknown. We used femtosecond-stimulated Raman spectroscopy to obtain time-resolved vibrational spectra of the molecular structures formed along the reaction coordinate. The spectral evolution of the vibrational features from 200 femtoseconds to 1 picosecond after photon absorption reveals the temporal sequencing of the geometric changes in the retinal backbone that activate this receptor. Understanding the mechanism of a chemical reaction requires measuring the structure of the reactant as it evolves into product. Many of the most intriguing and efficient photochemical and photobiological reactions take place on ultrafast time scales and their kinetics have been well characterized by femtosecond absorption and fluorescence spectroscopies (1-5). Although x-ray diffraction is being developed for timeresolved structural studies of reactions, this approach is challenging to apply in the condensed phase and currently limited to processes slower than È100 ps (6). Ultrafast vibrational spectroscopy is advantageous in this quest because it offers both excellent temporal and structural information (7). The traditional picosecond timeresolution limitation (8) is being transcended through the use of femtosecond pulses in the infrared (IR) in multidimensional as well as direct time-resolved experiments of ultrafast chemical and biological processes (9-11). The complementary Raman vibrational techniques have also advanced with the recent development of stimulated Raman in the femtosecond time domain (12, 13), which is valuable because of its ability to interrogate biological processes in aqueous media. Here, we demonstrate the capabilities of femtosecond-stimulated Raman spectroscopy (FSRS) in studies of reaction dynamics by elucidating the molecular mechanism of the primary photochemical events in vision. In FSRS, two laser pulses drive the Raman transition: a picosecond BRaman pulse[ and a femtosecond broadband continuum Bprobe pulse[ that stimulates the scattering of any vibrational modes with frequencies between 600 and 2000 cm j1 . The use of the additional probe pulse to induce the Raman scattering offers a number of notable improvements over traditional timeresolved spontaneous Raman spectroscopy (14), such as greatly enhanced cross sections and an order-of-magnitude improvement in time resolution (G100 fs) while maintaining excellent energy resolution (G15 cm j1 ) (15, 16). The impulsive creation of vibrational coherence by the Raman and probe pulses reveals highly time-resolved vibrational structural information that is not accessible by incoherent processes such as spontaneous Raman. The primary step in vision is the photochemical cis-trans isomerization of the 11-cis retinal chromophore in rhodopsin We address these questions by acquiring femtosecond time-resolved vibrational spectra of retinal in rhodopsin throughout the reaction. Modeling of the vibrational structural features after rapid internal conversion to the ground state reveals the highly distorted structure of photorhodopsin. Surprisingly, a large fraction of the atomic rearrangement leading to the formation of fully isomerized bathorhodopsin is shown to occur in the ground electronic state. Vivid details of thi

Global Regulation by Horizontally Transferred Regulators Establishes the Pathogenicity of Escherichia coli

Enterohemorrhagic Escherichia coli is an emerging pathogen that causes diarrhea and hemolytic uremic syndrome. Much of the genomic information that affects virulence is acquired by horizontal transfer. Genes necessary for attaching and effacing lesions are located in the locus for enterocyte effacement (LEE) pathogenicity island. LEE gene transcription is positively regulated by Ler, which is also encoded by the LEE, and by Pch regulators, which are encoded at other loci. Here we identified genes whose transcription profiles were similar to those of the LEE genes, by comparing the effects of altering ler and pch transcript levels. We assigned these genes into two classes, according to their transcription profiles. By determining the binding profiles for Ler and Pch, we showed that both were involved in regulating one class of genes, but only Pch was involved in regulating the other class. Binding sites were found in the coding region as well as the promoter region of regulated genes, which include genes common to K12 strains as well as 0157-specific genes, suggesting that both act as a global regulator. These results indicate that Ler and Pch orchestrate the transcription of virulence genes, which are captured by horizontal transfer and scattered throughout the chromosome

Pulmonary Sclerosing Hemangioma Detected by Fluorodeoxyglucose Positron Emission Tomography in Familial Adenomatous Polyposis: Report of a Case

We present a 53-year-old female suffering from familial adenomatous polyposis, who was found to have a positive nodus, lateral to the hilus of the left lung, on routine FDG-PET scan. This lesion was found to be a sclerosing hemangioma. We found an aberrant β-catenin expression on immunohistochemical staining, suggesting that sclerosing hemangioma and familial adenomatous polyposis share the same pathophysiology. It is important to be aware of the association of familial adenomatous polyposis and sclerosing hemangioma

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Clinicopathological characteristics of resected adenosquamous cell carcinoma of the lung: Risk of coexistent double cancer

<p>Abstract</p> <p>Background</p> <p>adenosquamous carcinoma (ADSQ) of non-small cell lung cancer (NSCLC) is a rare disease and the biological behavior and clinicopathological characteristics have not yet been thoroughly described.</p> <p>Method</p> <p>This study reviewed the patient charts of 11 (1.6%) ADSQ cases among 779 patients with primary lung cancer who underwent a lung resection. The characteristics and clinicopathological factors were evaluated retrospectively.</p> <p>Results</p> <p>Six of the 11 patients with ADSQ were male and five were female. The mean age was 67.3 years' olds. Three patients had pathological stage IA, one patient each had stage IB and IIA, five patients had stage IIIA, and one patient stage IIIB. Five patients had coexistent double cancer including 2 gastric, 1 rectal, 1 prostate and 1 bladder cancer. ADSQ was found less frequently in males than squamous cell carcinoma (SQ). ADSQ was found more frequently in older patients, with advanced stage, advanced T status, and lymph node metastases than adenocarcinoma (AD). The proportion with coexistent double cancer of AD, SQ, and ADSQ were 21.1, 17.6, and 45.5%, respectively. ADSQ had a significantly correlation with double cancer (ADSQ vs. non- ADSQ p = 0.03). A multivariate analysis showed no significant prognostic difference between the patients with ADSQ and non- ADSQ.</p> <p>Conclusions</p> <p>In this study, cases with ADSQ showed no significantly prognostic difference in comparison to AD and SQ. However, surgeons must be cautious of any coexistent double cancer because approximately half of all patients with ADSQ of the lung have double cancer.</p