78 research outputs found
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo
<p>Abstract</p> <p>Background</p> <p>Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), increases survival in patients with advanced EGFR-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the antitumor mechanism of this therapeutic drug.</p> <p>Results</p> <p>EGFR-expressing lung cancer cell lines were able to bind cetuximab and initiate complement activation by the classical pathway, irrespective of the mutational status of EGFR. This activation led to deposition of complement components and increase in complement-mediated cell death. The influence of complement activation on the activity of cetuximab <it>in vivo </it>was evaluated in xenografts of A549 lung cancer cells on nude mice. A549 cells express wild-type EGFR and have a KRAS mutation. Cetuximab activity against A549 xenografts was highly dependent on complement activation, since complement depletion completely abrogated the antitumor efficacy of cetuximab. Moreover, cetuximab activity was significantly higher on A549 cells in which a complement inhibitor, factor H, was genetically downregulated.</p> <p>Conclusions</p> <p>We demonstrate for the first time that the <it>in vivo </it>antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response.</p
Resultados a medio y largo plazo de la utilización de videotoracoscopia en la cirugía de resección de las metástasis pulmonares
The surgical resection of pulmonary metastases is a
method of treatment accepted as habitual in thoracic
surgery. However, it continues to be a source of
controversy if this resection must be realised by
thoracotomy or by modern video-assisted techniques.
With the aim of finding a response to this controversy in
our work milieu, a review was made of the surgical
interventions carried out in order to resect pulmonary
metastases. Between January 1997 and December 2001,
56 patients were found whose pulmonary metastases
had been resected by videothorascopy out of a total of
252 metastasectomies (22.2%). The primary tumours
were classified in 4 groups: sarcoma (n=11); colorectal
(n=25); renal (n=5); and others (n=15). Videothoroscopy
was carried out on the right hemithorax (n=28), left
hemithorax (n=22) or on both at once (n=6). Operational
mortality was nil and the only morbidity attributable to
the technique was a defect of re-expansion following the
removal of the thoracic drainage in one patient. Using
the Kaplan-Meier method, the probability of survival in
this series of patients was 60.4% after 5 years, with an
average survival time of 48 months. All of this data
supports the use of videothorascopy in our milieu on
patients with pulmonary metastases. However, in the
light of the results, it is important in using this technique
to place special emphasis on obtaining good margins of
resection, due to the real risk of local recurrence on
these margins in the medium term
Selection of extreme phenotypes: the role of clinical observation in translational research
Systematic collection of phenotypes and their correlation with molecular data has been proposed as a useful method to advance in the study of disease. Although some databases for animal species are being developed, progress in humans is slow, probably due to the multifactorial origin of many human diseases and to the intricacy of accurately classifying phenotypes, among other factors. An alternative approach has been to identify and to study individuals or families with very characteristic, clinically relevant phenotypes. This strategy has shown increased efficiency to identify the molecular features underlying such phenotypes. While on most occasions the subjects selected for these studies presented harmful phenotypes, a few studies have been performed in individuals with very favourable phenotypes. The consistent results achieved suggest that it seems logical to further develop this strategy as a methodology to study human disease, including cancer. The identification and the study with high-throughput techniques of individuals showing a markedly decreased risk of developing cancer or of cancer patients presenting either an unusually favourable prognosis or striking responses following a specific treatment, might be promising ways to maximize the yield of this approach and to reveal the molecular causes that explain those phenotypes and thus highlight useful therapeutic targets. This manuscript reviews the current status of selection of extreme phenotypes in cancer research and provides directions for future development of this methodology
Tratamiento del cáncer de próstata en función de la esperanza de vida, la comorbilidad y las guías de práctica clínica
En un número anterior de la revista de Anales del Sistema Sanitario de Navarra, Barceló y col realizaron una interesante y útil revisión de los pacientes con cáncer de próstata tratados en un gran centro hospitalario español durante un año, centrándose en sus características basales, el tratamiento realizado y el grado de seguimiento de las Guías de Práctica Clínica (GPC) y las complicaciones asociadas a los tratamientos realizados
Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology
Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often causes dose reductions and/or delays in administering the prescribed therapy, which can affect patient survival and quality of life. It is, therefore, important to prevent the occurrence of these adverse effects, or to treat unavoidable ones as soon as possible. This requires cooperation between medical oncologists and dermatologists. This article reviews the various dermatological toxicities associated with targeted therapies and immunotherapies, along with their diagnosis and therapeutic management
Frozen cancellous bone allografts: positive cultures of implanted grafts in posterior fusions of the spine
We have carried out a study on the behaviour pattern of implanted allografts
initially stored in perfect conditions (aseptically processed, culture-negative
and stored at -80 degrees C) but which presented positive cultures at the
implantation stage. There is no information available on how to deal with this
type of situation, so our aim was to set guidelines on the course of action which
would be required in such a case. This was a retrospective study of 112 patients
who underwent a spinal arthrodesis and in whom a total of 189 allograft pieces
were used. All previous bone and blood cultures and tests for hepatitis B and C,
syphilis and HIV (via PCR techniques) were negative. The allografts were stored
by freezing them at -80 degrees C. A sample of the allograft was taken for
culture in the operating theatre just before its implantation in all cases. The
results of the cultures were obtained 3-5 days after the operation. There were 22
allografts with positive culture results (12%) after implantation. These
allografts were implanted in 16 patients (14%). Cultures were positive for
staphylococci coagulase negative (ECN) in 10 grafts (46%), Pseudomonas stutzeri
in two grafts (9%), Corynebacterium jeikeium in two grafts (9%), staphylococci
coagulase positive in two grafts (9%) and for each of the following organisms in
one case each (4%): Corynebacterium spp., Actinomyces odontolyticus,
Streptococcus mitis, Peptostreptococcus spp., Rhodococcus equi and Bacillus spp.
No clinical infection was seen in any of these patients. Positive cultures could
be caused by non-detected contamination at harvesting, storing or during
manipulation before implantation. The lack of clinical signs of infection during
the follow-up of our patients may indicate that no specific treatment different
from our antibiotic protocol is required in the case of positive culture results
of a graft piece after implantation
Carcinoma microcítico de pulmón
El cáncer microcítico de pulmón es uno de los tumores sólidos más
agresivos, por su rápido crecimiento y por su tendencia a metastatizar
desde fases tempranas. Sin embargo, también es uno de los tumores
más sensibles a los tratamientos de quimioterapia y radioterapia, con
los cuales algunos pacientes con enfermedad limitada pueden sobre-
vivir a largo plazo. Estas características han hecho de este tumor un
modelo clínico sobre el cual se han probado múltiples estrategias de
tratamiento, incluyendo tratamientos concomitantes con quimioterapia
y radioterapia, esquemas de quimioterapia alternante o de altas dosis
con soporte hematológico o la utilización de radioterapia holocraneal
profi
láctica. Además en los últimos años el cáncer microcítico de pulmón
también se ha empleado como plataforma de desarrollo de tratamientos
dirigidos contra dianas específi
cas o de inmunoterapia. INGLÉS: Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches
The dynamic use of EGFR mutation analysis in cell-free DNA as a follow-up biomarker during different treatment lines in non-small-cell lung cancer patients
Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed
in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a
complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either
EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with
known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and
EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at
baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline
(median = 11, IQR = 9 5-13) to the best response (median = 0, IQR = 0-0, p < 0 01), followed by a significant increase at
progression (median = 11, IQR = 11-15, p < 0 01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained
with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital
PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA
multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients
independently of the drug received
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