Uveal vs. cutaneous melanoma. Origins and causes of the differences

Melanoma is a malignant tumour derived from melanocytes (dendritic cells originated from the neural crest and capable to produce melanin synthesis) that could be established on the skin or less frequently on the uvea. The cellular origin from both kind of melanoma seems to be the same but the melanocytes migrates to the epithelia for cutaneous melanoma, while for uveal melanoma, they migrate to mesodermic tissues. Despite the common origin, both melanomas show extreme differences in their metastatic potential, clinical response to treatments, immune response and genetic alterations. We will describe some of those differences in this review (AU)

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Viral gene therapy.

Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

Viral gene therapy

Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment (AU)

La actividad de la Caspasa-1 como gen sensibilizador a radio y quimioterapia es independiente de las vías de JNK y p38 / Caspase-1 as a radio and chemosensitizer regardless of JNK and p38 pathways

El efecto citotóxico de las drogas antitumorales es producido mediante la inducción de apoptosis. Esta observaciónimplica la posibilidad de que los factores que afecten la activación de caspasas pueden ser determinantesimportantes como sensibilizantes a los tratamientos antitumorales. Aquí, examinamos el efecto de la sobreexpresiónde caspasa-1 en la respuesta a la quimio y radioterapia. La expresión de la caspasa-1 mediada porun vector adenoviral fue capaz de matar directamente a las células y de sensibilizar las restantes a cisplatino oradiación gamma in vitro. En células HeLa transfectadas establemente con caspasa-1, la sensibilización a cisplatinofue debida a una amplificación en la vía mitocondrial de apoptosis inducida por cisplatino pero esteefecto es independiente del estado de p53, JNK o p38 en la célula

The cytotoxic effect of anticancer drugs has been shown to involve induction of apoptosis. This observationraises the possibility that factors affecting caspase activation might be important determinants as anticancerdrug sensitivity. Ectopic expression of caspase-1 has been shown to trigger apoptosis. Here, we examine theeffect of caspase-1 over-expression on the response to chemotherapy and radiotherapy. Caspase-1 expressionmediated by an adenoviral vector was able to kill directly cells and to sensitize the remaining cells to cisplatinor ã-radiation in vitro. In HeLa cells stably transfected with caspase-1, sensitisation to cisplatin was due to anamplification of the cisplatin-induced mitochondrial apoptotic pathway activation but this effect is independentof p53, JNK or p38 status

Routine perioperative pulmonary artery catheterization has no effect on rate of complications in vascular surgery: a meta-analysis.

Despite widespread use pulmonary artery catheterization has not been proven to reduce complications or mortality. One study supported the use of routine preoperative pulmonary artery catheterization in moderate-risk vascular surgery patients; several other studies have reported that pulmonary artery catheterization is not efficacious. Our goal was to scrutinize the data using meta-analysis. This is a systematic review of the literature. MEDLINE was searched for all articles on pulmonary artery catheterization, optimization, oxygen delivery, and preoperative preparation of vascular surgery patients. Data from papers judged appropriate for inclusion were analyzed using a computer program, Easy MA. Complications were defined as only those that could have reasonably have been prevented by or resulted from pulmonary artery catheterization. Of hundreds of possible papers only four were found to be adequate randomized prospective studies with similar exclusions, therapeutic endpoints, and interpretable complication and mortality rates. Controls included 174 patients versus 211 in the protocol group. Power analysis showed that the combined sample sizes were adequate. The meta-analysis demonstrates that the studies are homogeneous. The use of a pulmonary artery catheter does not prevent morbidity or mortality. Of the studies providing data on the amount of intravenous fluid administered three reported that statistically significantly more fluid was given to patients who underwent pulmonary artery catheterization. Meta-analysis indicates that in moderate-risk vascular surgery patients routine preoperative pulmonary artery catheterization is not associated with improved outcomes.

Significance of scapular fracture in the blunt-trauma patient.

STUDY OBJECTIVE: To determine the significance of scapular fractures in blunt-trauma patients compared with blunt-trauma patients without scapular fractures. DESIGN: Retrospective chart review of 11,500 blunt-trauma patients with a control group matched for age, sex, and mechanism of injury. SETTING: Two Level I trauma centers. PARTICIPANTS: Ninety-two blunt-trauma patients with scapular fractures and 81 control patients. RESULTS: Mortality, neurovascular injury, and injury severity scores were compared for blunt-trauma patients with scapular fractures with those of the control group. Analysis revealed a 1% incidence of scapular fractures in blunt trauma with no neurovascular injury and no mortality. Scapular fractures were associated with thoracic injury in 49% of the patients, compared with 6% in the control group (difference, 43%; 95% confidence interval, 31.6 to 51.4; P < .001, Fisher's exact test). CONCLUSION: Scapular fractures are not a significant marker of greater mortality or of neurovascular morbidity in blunt-trauma patients.