TTF-1/p63-positive poorly differentiated NSCLC: A histogenetic hypothesis from the basal reserve cell of the terminal respiratory unit

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast

Equilibrium hydrostatic equation and Newtonian limit of the singular f(R) gravity

We derive the equilibrium hydrostatic equation of a spherical star for any gravitational Lagrangian density of the form $L=\sqrt{-g}f(R)$. The Palatini variational principle for the Helmholtz Lagrangian in the Einstein gauge is used to obtain the field equations in this gauge. The equilibrium hydrostatic equation is obtained and is used to study the Newtonian limit for $f(R)=R-\frac{a^{2}}{3R}$. The same procedure is carried out for the more generally case $f(R)=R-\frac{1}{n+2}\frac{a^{n+1}}{R^{n}}$ giving a good Newtonian limit.Comment: Revised version, to appear in Classical and Quantum Gravity

Poliploidía inducida en amarantos

El objetivo del presente trabajo fue determinar el efecto de la inducción de poliploidía con colchicina sobre caracteres morfológicos y fisiológicos en 11 genotipos de Amaranthus. Los materiales genéticos utilizados fueron: A. caudatus L. cv Osear Blanco (TI) y cv Blanco Molinera (T2); A. mantegazzinus Passer cv Don manuel (T·), cv Don Juan (T4), cv panoja roja precoz (T5), cv panoja roja tardío (T6), A. hipocondriacus L. cv Artasa 9122 (T7), cv Anguil 59 (T8), cv Horticola (T9), A. cruentus L. cv Don Guiem (TIO) y cv Don Armando (TII). Los tratamientos fueron los siguientes: T: plantas tratadas con solución de colchicina al 2 % en el estado de plántula y NT: plantas no tratadas. El diseño dispuestas al azar en parcelas apareadas y con treinta repeticiones para cada cultivar. Las variables a medir fueron: altura de planta, días a floración de TI, 1'2, T3, T4 T5 YTlI, tamaño de estomas y células parenquimáticas del TI y peso de mil semillas. Los resultados se analizaron mediante" t" de Student para determinar el significado estadístico de las diferencias de medias entre plantas tratadas y no tratadas. Para el carácter altura de planta se encontraron diferencias significativas (p<0,05) en Tl0 (T= 92,5; NT= 103,8) Y en TII (T=64; NT=85,5) Y diferencias altamente significativas (p<0,01) en el T6 (T= 98,5; NT= 132,5). Para los días desde emergencia a floración se encontraron diferencias significativas (p<0,05) en el TI (T= 171,6; NT = 169,4) Y diferencias altamente significativas (p<0,01) en el 1'2 (T= 172; NT = 166,3) Y TII (T= 137,7; NT = 130,8). Para el peso de mil semillas no se encontraron diferencias significativas (p<0,05) entre T y NT para ninguno de los cultivares inducidos con colchicina. Para el carácter tamaño de estomas y células parenquimáticas del TI se encontraron diferencias altamente significativas (p<0,01) (T = 29,8 micrones NT = 21 micrones) y T= 62 micrones NT= 50,2, respectivamente. Esta efectividad debe corroborarse cultivando las semillas obtenidas analizando los mismos caracteres y efectuando un conteo de cromosomas.Director: Ing. Agr. Guillermo F. Covas. Cátedra de Genética y mejoramiento de plantas y animales. Facultad de Agronomía UNLPa

Relativistic dynamics of cylindrical shells of counter-rotating particles

Although infinite cylinders are not astrophysical entities, it is possible to learn a great deal about the basic qualitative features of generation of gravitational waves and the behavior of the matter conforming such shells in the limits of very small radius. We describe the analytical model using kinetic theory for the matter and the junction conditions through the shell to obtain its equation of motion. The nature of the static solutions are analyzed, both for a single shell as well as for two concentric shells. In this second case, for a time dependent external shell, we integrate numerically the equation of motion for several values of the constants of the system. Also, a brief description in terms of the Komar mass is given to account for the gravitational wave energy emitted by the system.Comment: 19 pages, 8 figure

Accelerated Cosmological Models in Ricci squared Gravity

Alternative gravitational theories described by Lagrangians depending on general functions of the Ricci scalar have been proven to give coherent theoretical models to describe the experimental evidence of the acceleration of universe at present time. In this paper we proceed further in this analysis of cosmological applications of alternative gravitational theories depending on (other) curvature invariants. We introduce Ricci squared Lagrangians in minimal interaction with matter (perfect fluid); we find modified Einstein equations and consequently modified Friedmann equations in the Palatini formalism. It is striking that both Ricci scalar and Ricci squared theories are described in the same mathematical framework and both the generalized Einstein equations and generalized Friedmann equations have the same structure. In the framework of the cosmological principle, without the introduction of exotic forms of dark energy, we thus obtain modified equations providing values of w_{eff}<-1 in accordance with the experimental data. The spacetime bi-metric structure plays a fundamental role in the physical interpretation of results and gives them a clear and very rich geometrical interpretation.Comment: New version: 26 pages, 1 figure (now included), Revtex

Nintedanib in NSCLC: Evidence to date and place in therapy

The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both preclinical and clinical phase I and II trials; however, its approval for the use in clinical practice has been possible because of the positive results of the LUME-Lung 1 trial (nintedanib + docetaxel versus docetaxel alone) in terms of progression-free survival and overall survival, and a manageable tolerability profile. Therefore, the good results seen in the clinical trials with nintedanib in the second-line setting for NSCLC patients with adenocarcinoma subtype are encouraging enough to recommend it in clinical practice

Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—Prevalence and geographic distribution of pathogenic variants in BRCA1/2 genes

Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlinico “P. Giaccone” of Palermo from January 1999 to October 2019. Thirty PVs were more frequently observed in the Sicilian population but only some of these showed a specific territorial prevalence, unlike other Italian and European regions. This difference could be attributed to the genetic heterogeneity of the Sicilian people and its historical background. Therefore hereditary breast and ovarian cancers could be predominantly due to BRCA1/2 PVs different from those usually detected in other geographical areas of Italy and Europe. Our investigation led us to hypothesize that a higher prevalence of some germline BRCA PVs in Sicily could be a population-specific genetic feature of BRCA-positive carriers