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2.
J Pers Med ; 14(2)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38392609

RESUMEN

Sepsis and septic shock are associated with high mortality, with diagnosis and treatment remaining a challenge for clinicians. Their management classically encompasses hemodynamic resuscitation, antibiotic treatment, life support, and focus control; however, there are aspects that have changed. This narrative review highlights current and avant-garde methods of handling patients experiencing septic shock based on the experience of its authors and the best available evidence in a context of uncertainty. Following the first recommendation of the Surviving Sepsis Campaign guidelines, it is recommended that specific sepsis care performance improvement programs are implemented in hospitals, i.e., "Sepsis Code" programs, designed ad hoc, to achieve this goal. Regarding hemodynamics, the importance of perfusion and hemodynamic coherence stand out, which allow for the recognition of different phenotypes, determination of the ideal time for commencing vasopressor treatment, and the appropriate fluid therapy dosage. At present, this is not only important for the initial timing, but also for de-resuscitation, which involves the early weaning of support therapies, directed elimination of fluids, and fluid tolerance concept. Finally, regarding blood purification therapies, those aimed at eliminating endotoxins and cytokines are attractive in the early management of patients in septic shock.

4.
J Appl Clin Med Phys ; 24(8): e14006, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37097754

RESUMEN

PURPOSE: To study and analyze the effect of the use of a thin guide-wire instead of a Foley catheter for urethral definition in prostate stereotactic body radiation therapy (SBRT) treatments and to compare treatment parameters in both situations. MATERIAL AND METHODS: Thirty-seven prostate SBRT patients were employed in this study. A Foley catheter was employed in nine of them, and a guide-wire was employed in the other 28 patients. For each of the 28 patients in which the guide-wire was employed, a comparison between urethral positions in both situations was performed, allowing for a margin definition of the urethra when a Foley catheter was employed. Displacements of the prostate during treatment were obtained, allowing for an analysis of prostate positions in both situations. Also, different treatment parameters such as the number of treatment interruptions, couch movements performed, and x-rays needed were gathered. RESULTS: Large differences between urethral positions can be found in the anterior-posterior (AP) directions compared to those in the lateral (LAT) direction. Differences are also larger in areas closer to the base of the prostate, where margins applied in the case of using a Foley catheter are 16 mm with a mean displacement of 6 mm in the posterior direction. No differences in the treatment parameters were found during treatment in both situations. The difference found in absolute prostate pitch rotations suggests that the Foley catheter provokes a shift of the prostate position, which does not occur when employing the guide-wire. CONCLUSIONS: Foley catheters shift the urethral position, making them a wrong surrogate of the urethra when no catheters are present. The margins needed to assess uncertainties introduced by the use of a Foley catheter are larger than those usually applied. The use of a Foley catheter did not present any additional difficulty during treatment delivery in terms of images employed or interruptions produced.


Asunto(s)
Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Uretra , Próstata , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Cateterismo Urinario
5.
Oncology ; 101(1): 1-11, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36063800

RESUMEN

INTRODUCTION: Cancer patients are more susceptible to infections, and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others. METHODS: We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers, and cancer-related features were analyzed. RESULTS: 2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2,527 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer, and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate were those diagnosed with lung cancer (OR 5.6 95% CI: 2.2-14.1). In the multivariate study, active oncological treatment (OR 2.259 95% CI: 1.35-3.77) and chemotherapy treatment (OR 3.624 95% CI: 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively. CONCLUSION: Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.


Asunto(s)
COVID-19 , Neoplasias Pulmonares , Humanos , COVID-19/epidemiología , Oncología Médica , Estudios Retrospectivos , SARS-CoV-2
6.
J Clin Transl Res ; 8(6): 465-469, 2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36452000

RESUMEN

Background and Aim: The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or 18fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation. Methods: Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol. Results: The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT (P=0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) (P=0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET. Conclusions: Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement. Relevance for Patients: The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment.

7.
Rep Pract Oncol Radiother ; 27(3): 527-544, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36186687

RESUMEN

Background: The development of brain metastases is a common problem in patients diagnosed with non-small cell lung carcinoma (NSCLC). Technological advances in surgery and radiotherapy have allowed greater local control. Moreover, the emergence of targeted therapies and immunotherapy with greater activity on the central nervous system than classical chemotherapy have given way to new strategies in the treatment of brain metastases. We review the current role of local treatments, surgery and radiotherapy, and the most effective combination strategies with the new systemic treatments. Relevance for patients: Brain metastases frequently occur during the course of NSCLC. In recent years, a range of treatments have appeared, such as targeted treatments or immunotherapy, with greater activity at the brain level than classical chemotherapy. Radiotherapy treatment is also now much more conformal and ablative doses can be delivered to the volume of the metastatic area, providing greater local control and less neurological toxicity. However, surgery is still required in cases where anatomopathological specimens are needed and when compressive effects appear. An important challenge is how to combine these treatments to achieve the best control and minimise patients' neurological impairments, especially because of limited experience with the new target drugs, and the unknown toxicity of the different combinations. Future research should therefore focus on these areas in order to establish the best strategies for the treatment of brain metastases from non-small cell lung cancer. Core tips: In this work, we intend to elucidate the best therapeutic options for patients diagnosed with brain metastases of NSCL, which include: surgery, WBRT, radiosurgery or systemic treatment, and the most effective combinations and timings of them, and the ones with the lowest associated toxicity.

8.
World J Clin Oncol ; 13(7): 652-662, 2022 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-36157159

RESUMEN

BACKGROUND: Approximately 30% of patients with localized prostate cancer (PCa) who undergo radical prostatectomy will develop biochemical recurrence. In these patients, the only potentially curative treatment is postoperative radiotherapy (PORT) with or without hormone therapy. However, the optimal radiotherapy dose is unknown due to the limited data available. AIM: To determine whether the postoperative radiotherapy dose influences biochemical failure-free survival (BFFS) in patients with PCa. METHODS: Retrospective analysis of patients who underwent radical prostatectomy for PCa followed by PORT-either adjuvant radiotherapy (ART) or salvage radiotherapy (SRT)-between April 2002 and July 2015. From 2002 to 2010, the prescribed radiation dose to the surgical bed was 66-70 Gy in fractions of 2 Gy; from 2010 until July 2015, the prescribed dose was 70-72 Gy. Patients were grouped into three categories according to the total dose administered: 66-68 Gy, 70 Gy, and 72 Gy. The primary endpoint was BFFS, defined as the post-radiotherapy prostate-specific antigen (PSA) nadir + 0.2 ng/mL. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS; based on conventional imaging tests). Treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity was evaluated according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Finally, we aimed to identify potential prognostic factors. BFFS, OS, CSS, and MFS were calculated with the Kaplan-Meier method and the log-rank test. Univariate and multivariate Cox regression models were performed to explore between-group differences in survival outcome measures. RESULTS: A total of 301 consecutive patients were included. Of these, 93 (33.6%) received ART and 186 (66.4%) SRT; 22 patients were excluded due to residual macroscopic disease or local recurrence in the surgical bed. In this subgroup (n = 93), 43 patients (46.2%) were Gleason score (GS) ≤ 6, 44 (47.3%) GS 7, and 6 (6.5%) GS ≥ 8; clinical stage was cT1 in 51 (54.8%), cT2 in 35 (39.3%), and cT3 in one patient (1.1%); PSA was < 10 ng/mL in 58 (63%) patients, 10-20 ng/mL in 28 (30.6%), and ≥ 20 ng/mL in 6 (6.4%) patients. No differences were found in BFFS in this patient subset versus the entire cohort of patients (P = 0.66). At a median follow-up of 113 months (range, 4-233), 5- and 10-year BFFS rates were 78.8% and 73.7%, respectively, with OS rates of 93.3% and 81.4%. The 5-year BFFS rates in three groups were as follows: 69.6% (66-68 Gy), 80.5% (70 Gy) and 82.6% (72 Gy) (P = 0.12):the corresponding 10-year rates were 63.9%, 72.9%, and 82.6% (P = 0.12), respectively. No significant between-group differences were observed in MFS, CSS, or OS. On the univariate analysis, the following variables were significantly associated with BFFS: PSA at diagnosis; clinical stage (cT1 vs cT2); GS at diagnosis; treatment indication (ART vs SRT); pre-RT PSA levels; and RT dose 66 -68 Gy vs. 72 Gy (HR: 2.05; 95%CI: 1.02-4.02, P = 0.04). On the multivariate analysis, the following variables remained significant: biopsy GS (HR: 2.85; 95%CI: 1.83-4.43, P < 0.001); clinical stage (HR: 2.31; 95%CI: 1.47-4.43, P = 0.01); and treatment indication (HR: 4.11; 95%CI: 2.06-8.17, P < 0.001). Acute grade (G) 1 GU toxicity was observed in 11 (20.4%), 17 (19.8%), and 3 (8.3%) patients in each group (66-68 Gy, 70 Gy and 72 Gy), respectively (P = 0.295). Acute G2 toxicity was observed in 2 (3.7%), 4 (4.7%) and 2 (5.6%) patients, respectively (P = 0.949). Acute G1 GI toxicity was observed in 16 (29.6%), 23 (26.7%) and 2 (5.6%) patients in each group, respectively (P = 0.011). Acute G2 GI toxicity was observed in 2 (3.7%), 6 (6.9%) and 1 (2.8%) patients, respectively (P = 0.278). No cases of acute G3 GI toxicity were observed. CONCLUSION: The findings of this retrospective study suggest that postoperative radiotherapy dose intensification in PCa is not superior to conventional radiotherapy treatment.

9.
World J Clin Oncol ; 13(4): 237-266, 2022 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-35582651

RESUMEN

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.

10.
J Clin Oncol ; 39(28): 3118-3127, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34379442

RESUMEN

PURPOSE: Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS: This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS: Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION: Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.


Asunto(s)
Neoplasias Encefálicas/prevención & control , Irradiación Craneana , Hipocampo/efectos de los fármacos , Neoplasias Pulmonares/radioterapia , Traumatismos por Radiación/prevención & control , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Cognición/efectos de la radiación , Irradiación Craneana/efectos adversos , Irradiación Craneana/mortalidad , Fraccionamiento de la Dosis de Radiación , Femenino , Hipocampo/fisiopatología , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Recuerdo Mental/efectos de la radiación , Persona de Mediana Edad , Tratamientos Conservadores del Órgano , Calidad de Vida , Traumatismos por Radiación/etiología , Traumatismos por Radiación/fisiopatología , Traumatismos por Radiación/psicología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/secundario , España , Factores de Tiempo , Resultado del Tratamiento
11.
J Hepatol ; 74(6): 1429-1441, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33515644

RESUMEN

BACKGROUND & AIMS: Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. METHODS: STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). RESULTS: Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, ß-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. CONCLUSIONS: The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. LAY SUMMARY: Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.


Asunto(s)
Ácidos y Sales Biliares/biosíntesis , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/metabolismo , Mitocondrias/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fosfoproteínas/metabolismo , Transducción de Señal/genética , Adulto , Anciano , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Células Cultivadas , Estudios de Cohortes , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Femenino , Eliminación de Gen , Hepatocitos/metabolismo , Humanos , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/genética , Fosfoproteínas/genética , Adulto Joven
12.
Exp Gerontol ; 142: 111118, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33091525

RESUMEN

With aging the immune response is impaired. This immunosenescence, in which an alteration of the redox state of the immune cells appears, is involved in the rate of aging. Since leukocyte function is a good marker of health and predictor of longevity, the effects of daily oral administration of the antioxidant vitamin C (500 mg), or both vitamin C (500 mg) and vitamin E (200 mg) on several blood neutrophil (adherence, chemotaxis, phagocytosis, and superoxide anion levels) and lymphocyte (adherence, chemotaxis, proliferation, interleukin-2 secretion and natural killer activity) functions were studied in healthy elderly men and women. These parameters were analysed before supplementation, after 3 months of supplementation, and 6 months after the end of supplementation. The results showed that vitamin C, in elderly participants, improved the immune functions studied which achieved values close to those of young adults. These effects were maintained in several functions after 6 months without supplementation. Similar effects were found in the elderly supplemented with both vitamin C and E. Thus, a short period of vitamin C or vitamin C and E ingestion, with the doses used, improves the immune function in elderly men and women and could contribute to a healthy longevity.


Asunto(s)
Ácido Ascórbico , Vitamina E , Anciano , Antioxidantes , Suplementos Dietéticos , Femenino , Humanos , Linfocitos , Masculino
13.
Oncotarget ; 11(11): 1006, 2020 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-32215189

RESUMEN

[This corrects the article DOI: 10.18632/oncotarget.3698.].

14.
Clin Lung Cancer ; 19(5): e693-e697, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29891263

RESUMEN

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of the usual treatment in most patients with small-cell lung cancer (SCLC) and response after treatment of the primary tumor. Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy might play a role in radiation-induced neurocognitive decline. PATIENTS AND METHODS: This study is a multicenter phase III trial (NCT02397733) randomizing SCLC patients after informed consent, to receive standard PCI treatment or PCI with hippocampus avoidance (PCI-HA) by using intensity modulated radiation therapy or volumetric modulated arc therapy. The primary objective is assessment of hippocampus-dependent memory functioning and safety after PCI with or without hippocampus sparing by the Free and Cued Selective Reminding Test. Secondary objectives are assessment of other neurotoxicity/quality of life, radiological brain abnormalities on magnetic resonance images, and evaluation of the incidence and location of brain metastases after PCI-HA compared with standard PCI. The originally planned sample size (n = 150) has been calculated to detect a 50% difference in the 3-month delayed recall score between the 2 treatment arms, with a statistical power of 80% (ß = 20%) and a significance level of 5% (α = 5%), with a maximum loss to follow-up of 10%. CONCLUSION: This study is an important step in introducing a new therapeutic approach to patients with SCLC candidates for PCI.


Asunto(s)
Irradiación Craneana/métodos , Hipocampo/efectos de la radiación , Neoplasias Pulmonares/radioterapia , Tratamientos Conservadores del Órgano/métodos , Selección de Paciente , Proyectos de Investigación , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Calidad de Vida , Planificación de la Radioterapia Asistida por Computador , Carcinoma Pulmonar de Células Pequeñas/patología , Adulto Joven
15.
Redox Biol ; 14: 164-177, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28942194

RESUMEN

Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC), by depleting mitochondrial GSH (mGSH) due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown. Although the transport of mGSH is not fully understood, SLC25A10 (dicarboxylate carrier, DIC) and SLC25A11 (2-oxoglutarate carrier, OGC) have been involved in mGSH transport, and therefore we examined their expression and role in HCC. Unexpectedly, HCC cells and liver explants from patients with HCC exhibit divergent expression of these mitochondrial carriers, with selective OGC upregulation, which contributes to mGSH maintenance. OGC but not DIC downregulation by siRNA depleted mGSH levels and sensitized HCC cells to hypoxia-induced ROS generation and cell death as well as impaired cell growth in three-dimensional multicellular HCC spheroids, effects that were reversible upon mGSH replenishment by GSH ethyl ester, a membrane permeable GSH precursor. We also show that OGC regulates mitochondrial respiration and glycolysis. Moreover, OGC silencing promoted hypoxia-induced cardiolipin peroxidation, which reversed the inhibition of cholesterol on the permeabilization of MOM-like liposomes induced by Bax or Bak. Genetic OGC knockdown reduced the ability of tumor-initiating stem-like cells to induce liver cancer. These findings underscore the selective overexpression of OGC as an adaptive mechanism of HCC to provide adequate mGSH levels in the face of mt-cholesterol loading and suggest that OGC may be a novel therapeutic target for HCC treatment.


Asunto(s)
Colesterol/metabolismo , Glutatión/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Mitocondrias/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular , Transportadores de Ácidos Dicarboxílicos/antagonistas & inhibidores , Transportadores de Ácidos Dicarboxílicos/genética , Transportadores de Ácidos Dicarboxílicos/metabolismo , Células Hep G2 , Humanos , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Proteínas de Transporte de Membrana/química , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/patología , Membranas Mitocondriales/metabolismo , Estrés Oxidativo , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Ratas
17.
Arch Bronconeumol ; 52 Suppl 1: 2-62, 2016 May.
Artículo en Inglés, Español | MEDLINE | ID: mdl-27389767
18.
Arch. bronconeumol. (Ed. impr.) ; 52(7): 378-388, jul. 2016. tab, ilus
Artículo en Español | IBECS | ID: ibc-154238

RESUMEN

La Sociedad Española de Neumología y Cirugía Torácica (SEPAR), a través de las áreas de Cirugía Torácica y de Oncología Torácica, ha promovido la realización de un manual de recomendaciones para el diagnóstico y el tratamiento del cáncer de pulmón de células no pequeñas. Las elevadas incidencia y mortalidad de esta patología hacen necesaria una constante actualización de las mejores evidencias científicas para su consulta por parte de los profesionales de la salud. Para su confección se ha contado con un amplio grupo de profesionales de distintas especialidades que han elaborado una revisión integral, que se ha concretado en 4 apartados principales. En el primero se ha estudiado la prevención y el cribado de la enfermedad, incluyendo los factores de riesgo, el papel de la deshabituación tabáquica y el diagnóstico precoz mediante programas de cribado. En un segundo apartado se ha analizado la presentación clínica, los estudios de imagen y el riesgo quirúrgico, incluyendo el cardiológico y la evaluación funcional respiratoria. Un tercero trata sobre los estudios de confirmación cito-histológica y de estadificación, con un análisis de las clasificaciones TNM e histológica, métodos no invasivos y mínimamente invasivos, así como las técnicas quirúrgicas para el diagnóstico y estadificación. En un cuarto y último capítulo se han abordado aspectos del tratamiento, como el papel de las técnicas quirúrgicas, la quimioterapia, la radioterapia, el abordaje multidisciplinar por estadios y otros tratamientos dirigidos frente a dianas específicas, terminando con recomendaciones acerca del seguimiento del cáncer de pulmón y los tratamientos paliativos quirúrgicos y endoscópicos en estadios avanzados


The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages


Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Pautas de la Práctica en Medicina , Práctica Clínica Basada en la Evidencia , Cese del Hábito de Fumar
19.
Arch Bronconeumol ; 52(7): 378-88, 2016 Jul.
Artículo en Inglés, Español | MEDLINE | ID: mdl-27237592

RESUMEN

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Biomarcadores de Tumor/sangre , Broncoscopía , Carcinoma de Pulmón de Células no Pequeñas/prevención & control , Quimioradioterapia , Técnicas de Diagnóstico del Sistema Respiratorio/normas , Detección Precoz del Cáncer , Humanos , Neoplasias Pulmonares/prevención & control , Estadificación de Neoplasias , Cuidados Paliativos , Neumonectomía/normas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neumología/organización & administración , Terapia Recuperativa , Cese del Hábito de Fumar , Sociedades Médicas , España , Tomografía Computarizada por Rayos X
20.
Arch. bronconeumol. (Ed. impr.) ; 52(supl.1): 2-62, mayo 2016. tab, graf
Artículo en Español | IBECS | ID: ibc-158439
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