0000000000916745
AUTHOR
Ignacio Petschen
Primitive neuroectodermal kidney tumor
To the Editor: Primitive neuroectodermal tumors (PNET) and Ewing sarcoma (ES) belong to a group of neoplasms de®ned by neuroectodermal differentiation and a characteristic cytogenetic translocation, t(11;22) (q24;q12) or gene rearrangements between chromosomes 21 and 22 [1]. They are generally aggressive tumors that present as metastatic disease in nearly 50% of the cases. ES is frequently a bone disease, whereas PNET can occur in bones, soft tissues, or any other site. Renal PNETs are extremely rare, with only a few cases reported [2]. We here record an adult with renal PNET and bone metastases at diagnosis. Because these tumor can also be found in children [3] our experience may therefore…
Glutamine potentiates TNF-α-induced tumor cytotoxicity
L-glutamine (Gln) sensitizes tumor cells to tumor necrosis factor (TNF)-alpha-induced cytotoxicity. The type and mechanism of cell death induced by TNF-alpha was studied in Ehrlich ascites tumor (EAT)-bearing mice fed a Gln-enriched diet (GED; where 30% of the total dietary nitrogen was from Gln). A high rate of Gln oxidation promotes a selective depletion of mitochondrial glutathione (mtGSH) content to approximately 58% of the level found in tumor mitochondria of mice fed a nutritionally complete elemental diet (standard diet, SD). The mechanism of mtGSH depletion involves a glutamate-induced inhibition of GSH transport from the cytosol into mitochondria. The increase in reactive oxygen in…
Changes in glutathione status and the antioxidant system in blood and in cancer cells associate with tumour growth in vivo
The relationship among cancer growth, the glutathione redox cycle and the antioxidant system was studied in blood and in tumour cells. During cancer growth, the glutathione redox status (GSH/GSSG) decreases in blood of Ehrlich ascites tumour-bearing mice. This effect is mainly due to an increase in GSSG levels. Two reasons may explain the increase in blood GSSG: (a) the increase in peroxide production by the tumour that, in addition to changes affecting the glutathione-related and the antioxidant enzyme activities, can lead to GSH oxidation within the red blood cells; and (b) an increase of GSSG release from different tissues into the blood. GSH and peroxide levels are higher in the tumour …
Bcl-2 and glutathione depletion sensitizes B16 melanoma to combination therapy and eliminates metastatic disease.
Abstract Purpose: Advanced melanoma resists all current therapies, and metastases in the liver are particularly problematic. Prevalent resistance factors include elevated glutathione (GSH) and increased expression of bcl-2 in melanoma cells. GSH has pleiotropic effects promoting cell growth and broad resistance to therapy, whereas Bcl-2 inhibits the activation of apoptosis and contributes to elevation of GSH. This study determined the in vivo efficacy of combination therapies administered while GSH and Bcl-2 were individually and simultaneously decreased in metastatic melanoma lesions. Experimental Design: Highly metastatic murine B16 melanoma (B16M-F10) cells have elevated levels of both G…