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1.
Am J Transplant ; 24(6): 1087-1090, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38219868

RESUMEN

Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Vena Porta , Trombosis de la Vena , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/complicaciones , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/complicaciones , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Vena Porta/patología , Masculino , Trombosis de la Vena/etiología , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/terapia , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pronóstico
2.
Ann Oncol ; 31(8): 1030-1039, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32339648

RESUMEN

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Anticuerpos Monoclonales Humanizados , Axitinib , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Neoplasias Renales/tratamiento farmacológico , Sunitinib/uso terapéutico
3.
J Indian Assoc Pediatr Surg ; 21(1): 41-3, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26862296

RESUMEN

Reconstruction of hepatic veins in living donor liver transplantation (LDLT) is often technically challenging and a good venous outflow is essential for survival of the graft and patient. We describe a quadrangular patch venoplasty technique used for the reconstruction of a rare variant of the left hepatic vein (LHV) in a pediatric LDLT with left lateral segment (LLS) graft. Segment II vein in the graft was draining directly into the inferior vena cava (IVC) and segment III vein was draining into the middle hepatic vein (MHV) after receiving a tributary from segment IV so that there were two widely separated ostia at the cut surface. This is one of the rarest variations of the LHV and is so called type 3 variant; it is usually reconstructed using interposition tubular conduits necessitating two separate anastomoses at the IVC.

4.
Klin Onkol ; 36(1): 35-44, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36868831

RESUMEN

BACKGROUND: Cancer mortality has doubled in India, a lower and middle-income country, from 1990 to 2016, depicting the ever-increasing burden of non-communicable disease. Karnataka, situated in the south of India, is one of the states with a rich medical college and hospital milieu. We present the status of cancer care across the state from the data collected by the investigators through public registries and personal communication to the concerned units to know the distribution of various services across the districts and give probable directives to improve on the present situation with emphasis on radiation therapy. This study may be taken as a bird's eye view of the situation across the country and form a basis based on which future planning of services and areas to emphasize on, may be considered. PURPOSE: The establishment of a radiation therapy center holds the key to the establishment of comprehensive cancer care centers. The existing situation of such centers and the need and scope for inclusion and expansion of cancer units is presented in this article.


Asunto(s)
Creación de Capacidad , Neoplasias , Humanos , India , Sistema de Registros , Investigadores
5.
ESMO Open ; 7(5): 100564, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36037566

RESUMEN

BACKGROUND: C-reactive protein (CRP) is an important prognostic and predictive factor in advanced renal cell carcinoma (aRCC). We report the association of CRP levels at baseline and early after treatment with efficacy of avelumab plus axitinib or sunitinib from the phase III JAVELIN Renal 101 trial. PATIENTS AND METHODS: Patients were categorized into normal (baseline CRP <10 mg/l), normalized (baseline CRP ≥10 mg/l and ≥1 CRP value decreased to <10 mg/l during 6-week treatment), and non-normalized (CRP ≥10 mg/l at baseline and during 6-week treatment) CRP groups. Progression-free survival and best overall response from the second interim analysis and overall survival (OS) from the third interim analysis were assessed. RESULTS: In the avelumab plus axitinib and sunitinib arms, respectively, 234, 51, and 108 patients and 232, 36, and 128 patients were categorized into normal, normalized, and non-normalized CRP groups. In respective CRP groups, objective response rates [95% confidence interval (CI)] were 56.0% (49.4% to 62.4%), 66.7% (52.1% to 79.2%), and 45.4% (35.8% to 55.2%) with avelumab plus axitinib and 30.6% (24.7% to 37.0%), 41.7% (25.5% to 59.2%), and 19.5% (13.1% to 27.5%) with sunitinib; complete response rates were 3.8%, 11.8%, and 0.9% and 3.0%, 0%, and 1.6%, respectively. Median progression-free survival (95% CI) was 15.2 months (12.5-21.0 months), not reached (NR) [11.1 months-not estimable (NE)], and 7.0 months (5.6-9.9 months) with avelumab plus axitinib and 11.2 months (8.4-13.9 months), 11.2 months (6.7-13.8 months), and 4.2 months (2.8-5.6 months) with sunitinib; median OS (95% CI) was NR (42.2 months-NE), NR (30.4 months-NE), and 23.0 months (18.4-33.1 months) and NR (39.0 months-NE), 39.8 months (21.7-NE), and 19.1 months (16.3-25.3 months), respectively. Multivariate analyses demonstrated that normalized or non-normalized CRP levels were independent factors for the prediction of objective response rate or OS, respectively, with avelumab plus axitinib. CONCLUSIONS: In patients with aRCC, CRP levels at baseline and early after treatment may predict efficacy with avelumab plus axitinib.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Axitinib/farmacología , Axitinib/uso terapéutico , Proteína C-Reactiva , Carcinoma de Células Renales/tratamiento farmacológico , Estudios de Seguimiento , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Sunitinib/farmacología , Sunitinib/uso terapéutico
6.
ESMO Open ; 6(3): 100101, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33901870

RESUMEN

BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Axitinib , Carcinoma de Células Renales , Neoplasias Renales , Sunitinib , Protocolos de Quimioterapia Combinada Antineoplásica , Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Sunitinib/uso terapéutico
7.
Sex Transm Infect ; 86(3): 193-8, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19965800

RESUMEN

OBJECTIVES: We undertook a prospective evaluation of the Qualpro Syphicheck-WB rapid syphilis test to measure its diagnostic performance and utility as a point-of-care (POC) screening test among female sex workers (FSWs) in Bangalore, India. METHODS: From August 2008 to May 2009, FSWs without a laboratory-confirmed history of syphilis attending STI clinics in Bangalore underwent POC syphilis screening using finger-prick whole blood, with onsite treatment if indicated. Serum samples were collected for local laboratory offsite rapid plasma reagin (RPR) testing and reference laboratory RPR, Treponema pallidum haemagglutination assay (TPHA), and rapid syphilis testing. FSWs who participated in standard offsite RPR screening from August 2007 to May 2008 in the same clinics formed the comparison group for treatment coverage. RESULTS: Of the 1617 women who underwent POC syphilis testing, 7.4% had laboratory evidence of active syphilis with reactive RPR and TPHA, and 3.7% had an RPR titre > or = 1:8. Compared with the reference RPR and TPHA, the sensitivity and specificity of the POC syphilis test were 70.8% (95% CI 62.7 to 79.0) and 97.8% (95% CI 97.1 to 98.5). Because of the low rate of women returning for their test results after offsite RPR screening, the proportion of women with active syphilis who were appropriately treated rose from 44.8% to 68.3% with the use of POC syphilis screening (p=0.003). CONCLUSION: The Syphicheck-WB test utilising finger-prick whole blood has a relatively low sensitivity in detecting active syphilis. However, among hard-to-reach populations who may not return for follow-up treatment, POC screening with this assay could still confer an advantage over offsite RPR testing with respect to treatment coverage.


Asunto(s)
Sistemas de Atención de Punto/normas , Trabajo Sexual/estadística & datos numéricos , Serodiagnóstico de la Sífilis/normas , Sífilis/prevención & control , Adulto , Femenino , Humanos , India/epidemiología , Tamizaje Masivo , Estudios Prospectivos , Sensibilidad y Especificidad , Sífilis/epidemiología , Serodiagnóstico de la Sífilis/métodos
8.
Ann Transl Med ; 7(17): 408, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31660307

RESUMEN

Cangrelor is a relatively new antiplatelet drug that has been approved for use as an adjunct therapy to percutaneous coronary intervention (PCI) to decrease peri-procedural myocardial infarction (MI), coronary revascularization, and stent thrombosis. Cangrelor is an adenosine triphosphate analogue with a pharmacokinetic mechanism based on a reversible, dose-dependent inhibition adenosine diphosphate (ADP)-induced platelet aggregation. This drug has lately been in the spotlight as a possible bridge therapy for anti-platelet medication prior to cardiac and non-cardiac surgeries. Platelet function is usually restored within sixty minutes of cessation of therapy, thereby decreasing the risk of bleeding while providing adequate pre-procedural coverage to reduce ischemic events. This manuscript reviews the literature on cangrelor and summarizes its role as a peri-procedural bridge.

9.
Toxicol Sci ; 91(2): 467-75, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16565513

RESUMEN

The goal of this study was to determine if the expression of the metallothionein (MT)-1/2 proteins might serve as a biomarker for the development of bladder cancer. A retrospective analysis of MT-1/2 staining was performed on 343 tissue sections from patients referred for the diagnosis of bladder cancer. The specimens were subdivided into six categories: benign, dysplastic, low-grade cancer, high-grade cancer with no evidence of invasion, high-grade cancer with evidence of invasion, and carcinoma in situ. There was no expression of MT-1/2 in benign lesions and low-grade cancers, a low incidence of expression in dysplastic lesions and high-grade cancers with no evidence of muscle invasion, and a significantly increased incidence of MT-1/2 in high-grade cancers that had invaded the underlying matrix. The expression of MT-1/2 varied in intensity from sample to sample and was focal in its expression. It was concluded from these findings that MT-1/2 may be a prognostic marker for cancers that are progressing to invade the underlying stroma of the bladder wall. The expression of MT-1/2 was also determined in a cell culture model of human urothelium that had been malignantly transformed by Cd2+ and As3+ and shown to be capable of tumor formation in nude mice. It was demonstrated that the expression of MT-1/2 in the tumor heterotransplants was similar to the pattern found in archival specimens of high-grade bladder cancers. The MT-1/2 staining in the heterotransplants was focal in pattern, varied in intensity, and highest in the less differentiated cells of the tumor. These findings indicate that the cell culture model may serve to help define the role of MT-1/2 expression in bladder cancer invasion.


Asunto(s)
Biomarcadores de Tumor , Metalotioneína/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Urotelio/metabolismo , Animales , Arsénico/toxicidad , Cadmio/toxicidad , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Línea Celular Transformada , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metalotioneína/genética , Ratones , Ratones Desnudos , Invasividad Neoplásica , Trasplante de Neoplasias , Pronóstico , ARN Mensajero/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Urotelio/efectos de los fármacos , Urotelio/patología
10.
J Phys Chem B ; 110(2): 772-6, 2006 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-16471601

RESUMEN

Layered double hydroxide (LDH)-monodispersed 4-nm CdSe nanoparticle composites were prepared through restacking of layers of colloidally dispersed delaminated LDH in the presence of CdSe nanoparticles in 1-butanol. The composites exhibit a blue shift for CdSe absorption, which increases with a decrease in nanoparticle content. The observed blue shift is due to the interaction of the quantum dots with the LDH layers, which leads to surface modification of the nanoparticles.

11.
J Colloid Interface Sci ; 294(1): 234-9, 2006 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-16084521

RESUMEN

The delamination-restacking behavior of a number of layered double hydroxides (LDHs) differing in [M(II)]/[M(III)] ratio, constituent metal ions and intercalated surfactant anions in different organic solvents has been studied. Colloidal dispersion due to delamination and the stability of the colloid obtained have been found to be not affected much by the nature of the constituent metal ions but increase with increase in the size of the surfactant anion. LDHs with low [M(II)]/[M(III)] ratio delaminate better than the ones with high [M(II)]/[M(III)] ratio. Delamination is best in alcohols such as 1-butanol, 1-hexanol, 1-octanol and 1-decanol, while a little delamination occurs in nonpolar solvents such as hexane. In all the cases, the original layered solid could be obtained through restacking of layers from the colloidal dispersion.

12.
Ultrastruct Pathol ; 30(3): 135-41, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16825114

RESUMEN

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.


Asunto(s)
Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Miopatías Mitocondriales/complicaciones , Músculo Esquelético/patología , Miocardio/patología , Oftalmoplejía Externa Progresiva Crónica/complicaciones , Deleción Cromosómica , Puente de Arteria Coronaria , ADN Mitocondrial/genética , Glucógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias Cardíacas/enzimología , Mitocondrias Cardíacas/ultraestructura , Mitocondrias Musculares/enzimología , Mitocondrias Musculares/ultraestructura , Músculo Esquelético/enzimología , Miocardio/enzimología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/ultraestructura
13.
Ultrastruct Pathol ; 30(6): 481-7, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17183762

RESUMEN

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.


Asunto(s)
Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/patología , Encefalomiopatías Mitocondriales/complicaciones , Músculo Esquelético/ultraestructura , Miocardio/ultraestructura , Oftalmoplejía Externa Progresiva Crónica/complicaciones , Biopsia , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , ADN Mitocondrial/genética , Complicaciones de la Diabetes/patología , Eliminación de Gen , Glucógeno/ultraestructura , Humanos , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mitocondrias Cardíacas/ultraestructura , Mitocondrias Musculares/ultraestructura , Oftalmoplejía Externa Progresiva Crónica/patología
15.
Toxicol Sci ; 87(1): 66-74, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15958653

RESUMEN

This study was designed to define the effect that overexpression of MT-3 would have on a cell culture model of bladder urothelium. Stable and inducible transfection was used to achieve overexpression of the MT-3 gene in the UROtsa cell line. When the UROtsa cells were stably transfected with the MT-3 coding sequence, there was highly elevated expression of MT-3 mRNA, but no MT-3 protein. An inducible vector showed that low basal levels of MT-3 mRNA and protein could be produced, but that induction only increased MT-3 mRNA and not protein. The clones expressing low basal levels of MT-3 protein also had reduced growth rates compared to control cells. Site directed mutagenesis was used to produce an MT-3 coding sequence where the prolines in positions 7 and 9 were converted to threonines. When this altered MT-3 was stably transfected into the UROtsa cells, the cells were able to accumulate the mutated form of the MT-3 protein. These studies show that MT-3 protein expression is inhibited by post-transcriptional control in the urothelial cell. Modifying the MT-3 protein to resemble the MT-1 isoform removes this component of post-transcriptional control and allows accumulation of the mutated MT-3 protein. The altered sequence involved in post-transcriptional control of MT-3 protein expression is the same sequence implicated in the neuronal growth inhibitory activity associated specifically with the MT-3 isoform of the MT gene family.


Asunto(s)
Metalotioneína/genética , Vejiga Urinaria/metabolismo , Cadmio/toxicidad , Línea Celular , Citomegalovirus/genética , Células Epiteliales/metabolismo , Humanos , Metalotioneína/análisis , Regiones Promotoras Genéticas , Isoformas de Proteínas , ARN Mensajero/análisis , Transcripción Genética , Transfección
16.
Cardiovasc Res ; 49(2): 476-83, 2001 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-11164858

RESUMEN

OBJECTIVES: Plasminogen activator inhibitor-1 (PAI-1) is a major anti-fibrinolytic glycoprotein thought to promote vascular diseases. Recently we have shown that systemically injecting mice with kainate, an analog of the principal brain excitatory neurotransmitter glutamate, immediately induced PAI-1 mRNA in brain vascular cells which are not known to contain glutamate receptors. Here we further investigated whether: (a) kainate also increases PAI-1 gene expression in the cardiac vascular bed; (b) subunits of kainate/AMPA receptors could be expressed in cardiac and brain vascular cells; and (c) PAI-1 mRNA could be similarly induced by agonists of adrenergic receptors that are candidates to act downstream in kainate-activated pathways. METHODS: We analyzed cardiac and brain cryosections for PAI-1 mRNA, as well as mRNAs encoding three receptor subunits, by in situ hybridization using 35S-labeled specific riboprobes. PAI-1 activity was tested in cardiac homogenates using one-phase reverse zymography. RESULTS: Prominent PAI-1 mRNA hybridization signals were induced in the vascular cells of the heart, and unexpectedly, also in cardiocytes, within 1-2 h after injection of kainate (i.p., 11-25 mg/kg body weight); the signals persisted for at least 8 h and disappeared after 24 h. In addition, PAI-1 activity increased ( approximately 5 fold) 2-10 h after the treatment. In contrast, mRNAs encoding the kainate/AMPA receptor subunits could not be detected. The adrenergic agents adrenaline (3.5 mg/kg) and isoproterenol (200 mg/kg) exerted kainate-like effects in cardiovascular cells. CONCLUSIONS: These results revealed, for the first time, that PAI-1 gene expression can be enhanced locally in the cardiovascular system by a fast-acting neurological mechanism triggered by glutamate receptors, whose pathway and relation to catecholamines, which exerted similar effects, have yet to be resolved. These findings raised the possibility that excessive glutamate, or stress-related catecholamines, may increase the risk of stroke and myocardial infarction.


Asunto(s)
Sistema Cardiovascular/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Kaínico/farmacología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Agonistas Adrenérgicos/farmacología , Agonistas Adrenérgicos beta/farmacología , Animales , Química Encefálica , Electroforesis en Gel de Poliacrilamida , Endotelio Vascular/química , Endotelio Vascular/metabolismo , Epinefrina/farmacología , Femenino , Hibridación in Situ , Isoproterenol/farmacología , Ratones , Músculo Liso Vascular/química , Músculo Liso Vascular/metabolismo , Miocardio/química , Miocardio/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , ARN Mensajero/análisis , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismo
17.
Hepatobiliary Surg Nutr ; 4(5): 354-62, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26605284

RESUMEN

Pancreatic hepatoid carcinoma (HC) is an extremely uncommon neoplasm of pancreas that resembles hepatocellular carcinoma (HCC). We report a case of incidentally detected pancreatic HC combined with a serous microcystic cystadenoma, in a 47-year-old man, while he was being evaluated for renal calculi. Contrast enhanced computed tomography (CECT) of abdomen revealed a lesion with mild heterogeneous enhancement in the tail of pancreas and another proximal lesion having moderate enhancement, and a calculus in the neck of gallbladder. Serum chromogranin, carcinoembryonic antigen (CEA) and CA 19-9 levels were within normal limits. He underwent laparoscopic distal pancreatectomy with splenectomy and cholecystectomy. Pathologically the distal tumor was encapsulated and characterized by eosinophilic cytoplasm, vesicular nucleus with prominent nucleolus and intranuclear eosinophilic inclusions. The cells were arranged in trabecular pattern separated by sinusoids. Canalicular and intercellular bile plugs were seen. On immunohistochemistry tumor cells were positive for hepatocyte specific antigen and weakly positive for alpha fetoprotein (AFP). The proximal tumor showed features of serous microcystic adenoma. Based on these findings, the case was diagnosed as hepatoid tumor of pancreas combined with serous microcystic cystadenoma. Post operative AFP was 1.75 IU/mL. The patient is on follow up for the last eight months and there is no evidence of recurrence.

18.
Cancer Chemother Pharmacol ; 76(4): 785-92, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26289594

RESUMEN

BACKGROUND: CP-4126 (gemcitabine elaidate, previously CO-101) is a lipid-drug conjugate of gemcitabine designed to circumvent human equilibrative nucleoside transporter1-related resistance to gemcitabine. The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of CP-4126, and to describe its pharmacokinetic profile. METHODS: Eligible patients with advanced refractory solid tumours, and adequate performance status, haematological, renal and hepatic function, were treated with one of escalating doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and 15 of a 28-day cycle. Blood and urine samples were collected to determine the pharmacokinetics (PKs) of CP-4126. RESULTS: Forty-three patients, median age 59 years (range 18-76; male = 27, female = 16), received one of ten dose levels (30-1600 mg/m(2)). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m(2) on basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven patients achieved stable disease sustained for ≥3 months, including two patients with pancreatic cancer who had progressed on or after gemcitabine exposure. CONCLUSIONS: CP-4126 was well tolerated with comparable toxicity profile to gemcitabine. Future studies are required to determine its anti-tumour efficacy, either alone or in combination with other cytotoxic chemotherapy regimens.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Desoxicitidina/análogos & derivados , Drogas en Investigación/administración & dosificación , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/farmacocinética , Antimetabolitos Antineoplásicos/uso terapéutico , Estudios de Cohortes , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Resistencia a Antineoplásicos , Drogas en Investigación/efectos adversos , Drogas en Investigación/farmacocinética , Drogas en Investigación/uso terapéutico , Femenino , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/metabolismo , Neoplasias/patología , Carga Tumoral/efectos de los fármacos , Adulto Joven
19.
Surg Endosc ; 16(1): 180-3, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11961635

RESUMEN

BACKGROUND: In the light of laparoscopic cholecystectomy increasingly applied to all forms of cholecystitis, this study aimed at evaluating the safety of laparoscopic cholecystectomy applied to all cases of acute cholecystitis, and at determining factors associated with the risk of conversion to open cholecystectomy. METHODS: The clinical, biochemical, radiologic, and operative data from 124 consecutive cases of acute cholecystitis were analyzed retrospectively to determine the complications and morbidity after operation. The data were analyzed further by univariate and multivariate analysis to identify factors associated with conversion. RESULTS: No major bile duct injury or mortality occurred. Bile leak from the stump of the cystic duct developed in four patients. These were managed successfully by endoscopic biliary stent placement. The mean duration of hospital stay was 3.8 days in the laparoscopic group and 8.2 days in the open group. Of the 124 patients (18.5%), 23 underwent conversion to open cholecystectomy. Univariate analysis identified the following factors as associated with conversion: common duct dilation greater than 7 mm observed on ultrasound, (p < 0.05), pericholecystic collection seen on ultrasound (p < 0.0001), emphysematous cholecystitis (p < 0.01), endoscopic retrograde cholangiopancreatographic evidence of Mirizzi syndrome (p < 0.05), and pericholecystic collection at operation (p < 0.0001). On multivariate analysis, only pericholecystic collection (p < 0.015) and gallbladder wall thickness greater than 5 mm (p < 0.013) were statistically significant. CONCLUSIONS: Laparoscopic cholecystectomy for acute cholecystitis can be applied safely to all comers, offering the advantage of a shortened hospital stay. Pericholecystic collection, as observed on ultrasound, is associated with a high risk of conversion to open cholecystectomy.


Asunto(s)
Colecistectomía Laparoscópica/métodos , Colecistitis/cirugía , Enfermedad Aguda , Anciano , Análisis de Varianza , Fístula Biliar/etiología , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
20.
Surg Endosc ; 17(6): 930-2, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12618936

RESUMEN

In light of the explosive increase in laparoscopic surgery, there is concern about the effectiveness of sterilizing reusable laparoscopic instruments by immersion in 2% glutaraldehyde. This article describes the clinical features of eight patients who presented with biopsy-proven tuberculosis at the port-site unassociated with other clinical features of tuberculosis. Three of the eight patients had positive cultures for Mycobacterium tuberculosis. The port-site sinuses healed with antituberculous chemotherapy. There is conflicting information in the literature regarding the effectiveness of a 20-min instrument soak in 2% glutaraldehyde to clear M. tuberculosis. In light of the preceding information, the current practice of glutaraldehyde disinfection for reusable laparoscopes needs to be reexamined.


Asunto(s)
Laparoscopía/efectos adversos , Infección de la Herida Quirúrgica/diagnóstico , Tuberculosis/diagnóstico , Adulto , Anciano , Femenino , Humanos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Infección de la Herida Quirúrgica/microbiología
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