Search results for " enzymes"

Profiling the physiological and molecular response to sulfonamidic drag in Procambarus clarkii

2014

Sulfamethoxazole (SMZ) is one of the most widely employed sulfonamides. Because of the widespread use of SMZ, a considerable amount is indeed expected to be introduced into the environment. The cytotoxicity of SMZ relies mainly on arylhydroxylamine metabolites (S-NOH) of SMZ and it is associated with the production of reactive oxygen species (ROS). There is limited information about the toxic potential of SMZ at the cellular and molecular levels, especially in aquatic and/or non-target organisms. In the present study, the red swamp crayfish (Procambarus clarkii), being tolerant to extreme environmental conditions and resistant to disease, was used as a model organism to profile the molecula…

Cathepsin L in metastatic bone disease: therapeutic implications

2010

AbstractCathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests that this endopeptidase might also be implicated in the regulation of other important biological functions, including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodeling processes, could contribute to facilitate bone metastasis formation. In support of this hypothesis, recent studies indicate that cathepsin L can foster this process by triggering multiple mechanisms which, in part, differ from those of t…

DOPAMINE PRO-DRUGS FOR CNS TARGETING: SYNTHESIS, CHARACTERIZATION AND HYDROLYSIS BY BRAIN ENZYMES.

2004

Why do results conflict regarding the prognostic value of the methylation status in colon cancers? The role of the preservation method.

2012

Abstract Background In colorectal carcinoma, extensive gene promoter hypermethylation is called the CpG island methylator phenotype (CIMP). Explaining why studies on CIMP and survival yield conflicting results is essential. Most experiments to measure DNA methylation rely on the sodium bisulfite conversion of unmethylated cytosines into uracils. No study has evaluated the performance of bisulfite conversion and methylation levels from matched cryo-preserved and Formalin-Fixed Paraffin Embedded (FFPE) samples using pyrosequencing. Methods Couples of matched cryo-preserved and FFPE samples from 40 colon adenocarcinomas were analyzed. Rates of bisulfite conversion and levels of methylation of …

The “unnatural” history of colorectal cancer in Lynch syndrome : lessons from colonoscopy surveillance

2021

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alon…

The Peroxisome Proliferator WY-14,643 Promotes Hepatocarcinogenesis Caused by Endogenously Generated Oxidative DNA Base Modifications in Repair-Defic…

2007

Abstract Basal levels of endogenously generated oxidative DNA modifications such as 7,8-dihydro-8-oxoguanine (8-oxoG) are present in apparently all mammalian cells, but their relevance for the generation of spontaneous cancers remains to be established. Both the 8-oxoG levels and the resulting spontaneous mutations are increased in the livers of Csbm/m/Ogg1−/− mice, which are deficient in the repair of 8-oxoG. In order to determine the consequences of these additional oxidative DNA modifications and mutations and thus assess the tumor initiating potency of this type of endogenous DNA damage, we treated Csbm/m/Ogg1−/− mice and repair-proficient controls with the peroxisome proliferator WY-14…

Temozolomide- and fotemustine-induced apoptosis in human malignant melanoma cells: response related to MGMT, MMR, DSBs, and p53

2009

Malignant melanomas are highly resistant to chemotherapy. First-line chemotherapeutics used in melanoma therapy are the methylating agents dacarbazine (DTIC) and temozolomide (TMZ) and the chloroethylating agents BCNU and fotemustine. Here, we determined the mode of cell death in 11 melanoma cell lines upon exposure to TMZ and fotemustine. We show for the first time that TMZ induces apoptosis in melanoma cells, using therapeutic doses. For both TMZ and fotemustine apoptosis is the dominant mode of cell death. The contribution of necrosis to total cell death varied between 10 and 40%. The O(6)-methylguanine-DNA methyltransferase (MGMT) activity in the cell lines was between 0 and 1100 fmol m…

pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-…

2003

The estrogen receptor-alpha (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-alpha gene expression are not fully understood. Here we show a new molecular mechanism of ER-alpha gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between p…

Lysosomal alterations in heart and liver of mice treated with doxorubicin.

1985

This study was carried out to evaluate the influence of long-term treatment with doxorubicin (DXR) (4mg/kg IV for 5 weeks) on heart and liver lysosomes of mice. We evaluated the variations in both total and "sedimentable" enzyme activity of cathepsin D, which is the major endopeptidase of myocites and probably involved in physiologic and pathologic degradation of actomyosin and mitochondria, and that of acid phosphatase, which is more prominent in interstitial cells. Our results show that marked changes occur in both total and sedimentable enzyme activity of cathepsin D in the heart of treated animals and to a lesser extent in the liver. In contrast, no modification of either total or sedim…

Sensitivity of liver metabolism in jerboa (Jaculus orientalis) to ciprofibrate, a peroxisome proliferator.

2009

International audience; Ciprofibrate is a well-known drug used to normalize lipid parameters and fibrinogen in atherosclerosis patients. In laboratory rodents such as rats or mice, ciprofibrate exhibits peroxisome proliferator activity. However, to date, no clear alterations or side effects caused by ciprofibrate have been noted in humans. In order to further investigate such possible relationships, we studied the effects of sustained ciprofibrate treatment in jerboas (Jaculus orientalis). In these rodents, ciprofibrate does not induce hepatomegaly or promote liver cell DNA replication, confirming that this species more closely resembles humans than do rats or mice. The jerboas were treated…