Mutated circulating tumor DNA as a liquid biopsy in lung cancer detection and treatment

Over the past decade, substantial developments have been made in the detection of circulating tumor DNA (ctDNA)-cell-free DNA (cfDNA) fragments released into the circulation from tumor cells and displaying the genetic alterations of those cells. As such, ctDNA detected in liquid biopsies serves as a powerful tool for cancer patient stratification, therapy guidance, detection of resistance, and relapse monitoring. In this Review, we describe lung cancer diagnosis and monitoring strategies using ctDNA detection technologies and compile recent evidence regarding lung cancer-related mutation detection in liquid biopsy. We focus not only on epidermal growth factor receptor (EGFR) alterations, but also on significant co-mutations that shed more light on novel ctDNA-based liquid biopsy applications. Finally, we discuss future perspectives of early-cancer detection and clonal hematopoiesis filtering strategies, with possible inclusion of microbiome-driven liquid biopsy. Liquid biopsy can greatly contribute to better detection and management of lung cancer. ctDNA detection in liquid biopsies is a powerful tool for early detection, cancer patient stratification, therapy guidance, detection of resistance, and relapse monitoring. We describe lung cancer diagnosis and monitoring strategies using ctDNA detection technologies and compile recent evidence on the identification of lung cancer-related mutations through liquid biopsy

Estudis sobre càncer de pulmó a la població espanyola milloren el tractament individualitzat

Abans d'aquest estudi, només s'havia analitzat prospectivament la presència de mutacions de l'oncogen EGFR per a l'adenocarcinoma en població asiàtica. Els investigadors han estudiat la incidència d'aquesta malaltia en població espanyola i la seva resposta al tractament amb erlotinib. Així, s'han establert les característiques del subgrup de pacients amb més possibilitats de trobar les mutacions implicades, el que facilita el seu tractament individualitzat i una supervivència sense progressió de la malaltia mai assolides al càncer de pulmó.Antes de este estudio, sólo se había analizado prospectivamente la presencia de mutaciones del oncogén EGFR para el adenocarcinoma en población asiática. Los investigadores han estudiado la incidencia de esta enfermedad en la población española y su respuesta al tratamiento con erlotinib. Así, se han establecido las características del subgrupo de pacientes con más posibilidades de encontrar las mutaciones implicadas, lo que facilita su tratamiento individualizado y una supervivencia sin progresión de la enfermedad nunca logradas en el cáncer de pulmón

On the structure of two-point Green-functions at next-to-leading order in 1/Nc

The structure of the two-point QCD Green-functions is studied in this note in the limit of large number of colours. Their general form at next-to-leading order in 1/Nc is derived keeping the infinite resonance summation and without relying on a particular realization of the hadronic action. It is found that the contributions from chiral operators without resonance fields of order p^4 or higher are irrelevant for the computation of the correlators and, hence, they can be dropped at the beginning of the calculation. The possibility of a more general cancelation of these local terms at the level of the generating functional is discussed.Comment: 6 pages, 1 figur

Estado de la neumología pública en Cataluña: estudio comparativo entre 1993 y 2003

ResumenEl objetivo de este estudio era realizar un análisis descriptivo de la situación de la neumología pública en Cataluña en el año 2003 y comparar los resultados con datos de 1993.Se remitió un cuestionario a todos los hospitales de la red pública de Cataluña (XHUP) solicitando información sobre el número de neumólogos. También se contactó con los servicios de atención primaria (SAP) de Cataluña para conocer el número de neumólogos que trabajan en atención primaria.Se ha obtenido respuesta del 100% de los hospitales y SAP contactados. El 83% de los hospitales de la XHUP disponen de servicio de neumología, y se observa un incremento significativo en la proporción de hospitales que disponen de la especialidad respecto a 1993. La tasa de neumólogos por 100.000 habitantes para toda Cataluña es de 3,15.El grado de implantación de la neumología en la XHUP ha mejorado significativamente en el decenio 1993-2003.AbstractThe aim of this study was to perform a descriptive analysis of the state of public pneumology in Catalonia (Spain) in 2003 and to compare the results with data from 1993.A questionnaire was sent to all hospitals of the public hospitals network in Catalonia requesting information on the number of pulmonologists. To determine the number of pulmonologists working in primary care, we also contacted all the primary care services (PCS) in Catalonia.All the hospitals and PCS contacted responded. Eighty-three percent of the public network hospitals had a pneumology service. From 1993-2003, the proportion of hospitals with this specialty increased. The rate of pulmonologists per 100,000 persons for the whole of Catalonia was 3.15.The degree of implantation of pneumology in the public hospitals network of Catalonia significantly improved in the decade between 1993 and 2003

Hadronic Light-by-Light Contribution to Muon g-2: Status and Prospects

I review the recent calculations and present status of the hadronic light-by-light contribution to the muon g-2.Comment: 8 pages, 1 figure. Invited talk at PHIPSI08, International Conference on e+e- collisions from Phi to Psi, April 7-10 2008, Frascati, Italy. v2: Wrong year in one referenc

Aluminosi, problema resolt o conflicte latent?

L’ensorrament del sostre d’un edifici del Turó de la Peira de Barcelona va desencadenar una gran alarma social a l’entorn de l’estat del parc edifica t. Una alarma que a poc a poc es va anar apaivagant amb mesures polítiques i tècniques que han permès assolir un bon coneixement dels edificis, del seu estat, de les seves mancances i de la manera de corregir- les. Avui, vint anys després, encara són molts els malentesos de caire tècnic i social que hi ha a l’entorn d’aquest tema i que cal clarificar per evitar les conseqüències perverses que comporten. L’aluminosi ha deixat de ser un problema tècnic per esdevenir un problema de caire socioeconòmic i judicial. El que va començar com un problema estructural dels edificis, la degradació de les biguetes fabricades amb ciment aluminós, –els mitjans de comunicació ho van popularitzar amb el nom d’aluminosi– ha passat a ser: un problema social, ja que els edificis on hi ha ciment aluminós són considerats edificis malalts i perillosos per als seus habitants; un problema econòmic, ja que les entitats financeres concedeixen un valor molt reduït a aquests edificis; i un problema judicial, perquè la simple presència de ciment aluminós en un edifici és considerada una patologia greu per part dels jutges. El concepte científic d’aluminosi el va definir per primer cop, l’any 1989, el químic Rafael Talero, com un fenomen que es podia produir en el formigó fabricat amb ciment aluminós i que necessitava tres processos patològics simultanis: la conversió, la carbonatació i la hidròlisi alcalina. El resultat és un formigó que, com deia Talero, es desfà dins de l’aigua com un terròs de sucre. Però també és cert que la hidròlisi alcalina que sí que existeix als laboratoris, fins ara no l’hem trobada en cap dels edificis ni en els milers de mostres analitzades.Peer ReviewedPostprint (published version

PET/CT Fusion Scan in Lung Cancer: Current Recommendations and Innovations

Abstract:Combined fluorodeoxyglucose-positron emission tomography (PET)/ computed tomography (CT) imaging has the potential to become the new standard imaging modality for the staging and restaging of patients with lung cancer. PET/CT is superior to PET alone, CT alone, and visual correlation of both techniques separately. In particular, it improves T3 and T4 staging and delineation of tumors associated with atelectasis. CT contrast media enhancement is probably only still needed when a substantial mediastinal tumor component is present and delineation of tumor from vascular structures is relevant. PET/CT is very accurate in detecting mediastinal nodal disease, but false-positive results are sufficiently frequent to require sampling in some positive cases. Whole-body PET/CT is the most sensitive technique for detecting extracranial metastatic disease, unexpected additional primary malignancies, and recurrence. Innovations include therapy monitoring, prognostic information, evaluation of small-cell lung cancer, its use for radiotherapy planning, and four-dimensional respiratory gating acquisition

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming.

The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming. Cells undergoing early adaptive drug escape are in proliferative-metabolic quiescent, with enhanced EMT-ness and stem cell signaling, exhibiting global bioenergetics suppression including reverse Warburg, and are susceptible to glutamine deprivation and TGFβ2 inhibition. Our study further supports a preemptive therapeutic targeting of bioenergetics and mitochondrial priming to impact early drug-escape emergence using EGFR precision inhibitor combined with broad BH3-mimetic to interrupt BCL-2/BCL-xL together, but not BCL-2 alone