Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiologic evidence in humans suggests a role for selenium in reducing cancer incidence and mortality. The aim of the present study was that to assess the ability of selenium dioxide (SeO2) to enhance the lymphocyte progression through the cell cycle in patients with advanced (stage IV) cancer. Ten patients (mean age 51.9 years, range: 32-74; M/F ratio: 3/7) with tumors at different sites were included in the study. The addition into culture of SeO2 1.5 microM enhanced significantly the progression into S phase of PBMCs isolated from cancer patients, whilst no significant effect was observed on PBMCs isolated from controls. ROS levels were significantly higher, whereas GPx activity was significantly lower in cancer patients than controls. Serum levels of IL-6 and TNFalpha were significantly higher in cancer patients than controls. Our results show the ability of selenium to induce a progression of PBMCs from cancer patients into the cell cycle, which is an essential prerequisite for the physiological functioning of the immune system and thus positively influence the immune status of advanced cancer patients. The mechanism of action of selenium could be to downregulate the production and release of proinflammatory cytokines, which have a role in cancer progression and particularly in the onset of cachexia.
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PMID:Selenium is effective in inducing lymphocyte progression through cell cycle in cancer patients: potential mechanisms for its activity. 1525 93

Cellular prion protein (PrP(C)), a glycosylphosphatidylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immuno histochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrP(C) expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrP(C) and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrP(C) suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrP(C)-transfected cells. A reverse effect was observed in PrP(C) siRNA-transfected cells. These results strongly suggested that PrP(C) might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma.
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PMID:Overexpression of PrPC and its antiapoptosis function in gastric cancer. 1658 85

Reactive oxygen species and tumor biology are intertwined in a complex web, making it difficult to understand which came first, whether oxidants are required for tumor cell growth, and whether oxidant stress can be exploited therapeutically. Evidence suggests that transformed cells use ROS signals to drive proliferation and other events required for tumor progression. This confers a state of increased basal oxidative stress, making them vulnerable to chemotherapeutic agents that further augment ROS generation or that weaken antioxidant defenses of the cell. In this respect, it appears that tumor cells may die by the same systems they require.
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PMID:Reactive oxygen species in cancer cells: live by the sword, die by the sword. 1695 15

Ceramides have been proposed as potential therapeutic strategy with regard to their ability to induce cell death. We previously demonstrated that C2-ceramide generated apoptosis in bronchocarcinoma BZR cells. We here investigated whether ceramides also target other molecules involved in cell-cell or cell-matrix interactions during cancer progression. A SuperArray(R) analysis showed that ceramides modulate gene expression after 2 h. Among deregulated genes, we observed an inhibition of the transcript coding for the pro-metastatic enzyme MMP-2. The pharmacological inhibitor of caspases cascade, ZVAD-fmk, did not prevent C2-ceramide-induced down-regulation of MMP-2 ruling out apoptosis as a mediator of this event, whereas inhibition of oxidative stress using NAC confirmed a role for ROS. This effect of C2-ceramide was associated with changes in histone H3 acetylation. However, although histone deacetylase inhibitors are also currently under investigation for their anti-tumor activity, we demonstrated here that a combined treatment with trichostatin A abrogated both MMP-2 down-regulation and reduced invasive properties elicited by C2-ceramide alone. Hence, this study demonstrates that besides its apoptotic effect, C2-ceramide also exhibits anti-invasive properties, showing a dual beneficial effect against cancer progression, but casts some doubt on the use of HDAC inhibitors as combined treatment with drugs that trigger the ceramide pathway.
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PMID:Ceramide inhibition of MMP-2 expression and human cancer bronchial cell invasiveness involve decreased histone acetylation. 1859 24

The decrease in the copy number of mitochondrial DNA (mtDNA) in cancer tissues might be associated with a decrease in oxidative mtDNA damage to achieve cancer immortalization and progression. Lung cancer specimens were collected from 29 patients with stage III non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgical resection. The relative mtDNA copy number and the oxidative mtDNA damage (formation of 8-OHdG in mtDNA) of each cancer tissue were measured by quantitative real-time PCR. Seven female and 22 male lung cancer patients, with a mean age of 63.5 years were evaluated. Tumors of five patients became progressive, 13 stable, and 11 partially responsive after preoperative chemotherapy. Low mtDNA copy number (P=0.089) and low degree of oxidative mtDNA damage (P=0.036) were found to associate with tumor progression. Moreover, mtDNA copy number was significantly related to the degree of oxidative mtDNA damage (P=0.031). The mtDNA copy number and oxidative mtDNA damage were lower in advanced NSCLC after chemotherapy. This finding suggests that a decrease in the content of mtDNA may result in a decrease of mitochondrial density in cancer cells, which leads to a decrease of endogenous ROS production and reduction of ROS-triggered DNA damage to achieve immortalization.
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PMID:Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. 1868 21

As we gain a better understanding of the factors affecting cancer etiology, we can design improved treatment strategies. Over the past three to four decades, there have been numerous successful efforts in recognizing important cellular proteins essential in cancer growth and therefore these proteins have been targeted for cancer treatment. However, studies have shown that targeting one or two proteins in the complex cancer cascade may not be sufficient in controlling and/or inhibiting cancer growth. Therefore, there is a need to examine features which are potentially involved in multiple facets of cancer development. In this review we discuss the targeting of the elevated copper (both in serum and tumor) and oxidative stress levels in cancer with the aid of a copper chelator d-penicillamine (d-pen) for potential cancer treatment. Numerous studies in the literature have reported that both the serum and tumor copper levels are elevated in a variety of malignancies, including both solid tumor and blood cancer. Further, the elevated copper levels have been shown to be directly correlated to cancer progression. Enhanced levels of intrinsic oxidative stress has been shown in variety of tumors, possibly due to the combination of factors such as elevated active metabolism, mitochondrial mutation, cytokines, and inflammation. The cancer cells under sustained ROS stress tend to heavily utilize adaptation mechanisms and may exhaust cellular ROS-buffering capacity. Therefore, the elevated copper levels and increased oxidative stress in cancer cells provide for a prospect of selective cancer treatment.
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PMID:Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. 1877 52

Inflammation is deeply entangled with redox modulation. Triggering of PRRs on inflammatory cells induces ROS generation. As a consequence, activated cells mount antioxidant responses to counteract the possible harmful effects of oxidation. Therefore, when repair is completed, homeostasis is restored. Here, we describe some recent results showing that an exuberant antioxidant response to pro-oxidant inflammatory stimuli modifies not only the intra- but also the extracellular redox and contributes to the outcome of the inflammatory process. In particular, the role of redox modulation in IL-1beta secretion, in B lymphocyte differentiation to plasma cells, and in tumor progression will be discussed, and the potential consequences of extracellular redox alterations on DAMP activity will be considered.
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PMID:DAMPs and inflammatory processes: the role of redox in the different outcomes. 1956 70

Vascular inflammation is an important event in the development of vascular diseases such as tumor progression and atherosclerosis. In the present study, betulinic acid (BA) treatment was found to show potent inhibitory effect on vascular inflammation process by TNF-alpha in human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with BA was blocked TNF-alpha induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial cell selectin (E-selectin) as well as gelatinase in TNF-alpha-activated HUVEC in a dose-dependent manner. When preincubated with BA, the adhesion of HL-60 cells to TNF-alpha-induced HUVEC was significantly decreased in a concentration-dependent manner. TNF-alpha-induced intracellular ROS was markedly decreased by pretreatment with BA. Furthermore, BA significantly inhibited the translocation and transcriptional activity of NF-kappaB increased by TNF-alpha. In conclusion, these results suggested a vascular protective role of BA via inhibition of ROS and NF-kappaB activation in HUVEC.
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PMID:Protective role of betulinic acid on TNF-alpha-induced cell adhesion molecules in vascular endothelial cells. 1989 62

Anoikis, an apoptosis triggered by loss of cell anchorage, has been shown to be a principal mechanism of inhibition of tumor metastasis. Recently, anti-apoptotic Bcl-2 and Cav-1 proteins have been demonstrated to be highly associated with tumor metastasis and apoptosis resistance. Curcumin, a major active component of turmeric, Curcuma longa, has been shown to inhibit neoplastic evolution and tumor progression; however, the underlying mechanisms are unclear. In this study, we investigated the effect of curcumin on cell anoikis as a possible mechanism of anti-tumorigenic action of curcumin, and evaluated the potential role of Bcl-2 and Cav-1 in this process. Our results showed that ectopic expression of either Bcl-2 or Cav-1 induced anoikis resistance of lung carcinoma H460 cells. Curcumin downregulated Bcl-2 protein during anoikis and sensitized the cells to detachment-induced apoptosis, whereas it had no significant effect on Cav-1 protein expression. Bcl-2 down-regulation as well as anoikis enhancement by curcumin were inhibited by superoxide anion scavenger, Mn(III)tetrakis(4-benzoic acid) porphyrin chloride, but were unaffected by other ROS scavengers including catalase and deferoxamine, suggesting that superoxide anion is a key player in the downregulation of Bcl-2 by curcumin. Furthermore, we provided evidence that curcumin decreased Bcl-2 level through ubiquitin-proteasomal degradation which sensitized cells to detachment-induced apoptosis. These findings indicate a novel pathway for curcumin regulation of Bcl-2 and provide a key mechanism of anoikis regulation that may be exploited for metastatic cancer treatment.
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PMID:Curcumin sensitizes non-small cell lung cancer cell anoikis through reactive oxygen species-mediated Bcl-2 downregulation. 2012 74

HIPK2 is a stress-induced kinase and a transcriptional corepressor that functionally cooperates with p53 to suppress cancer. Activation of the p53 proapoptotic function requires a cascade of phosphorylations and acetylations, and HIPK2 takes part in both modifications in that it phosphorylates p53 Ser46 and induces p53 Lys382 acetylation. Here, to further investigate the role of HIPK2 in p53 activation, we started with the finding that HIPK2 inhibition upregulated Nox1, a homolog of the catalytic subunit of the superoxide-generating NADPH oxidase, involved in tumor progression and ROS production. We found that Nox1 inhibited p53 Lys382 acetylation, which is a target of SIRT1 deacetylase, and impaired p53 proapoptotic transcriptional activity. By the use of either small interfering RNAs to target SIRT1 or the SIRT1 inhibitor nicotinamide we found that Nox1-dependent inhibition of p53 transcriptional activity was SIRT1-dependent. Thus, Nox1 was unable to inhibit p53 when coexpressed with a SIRT1 deacetylase-defective mutant (SIRT1HY), suggesting a link between Nox1 and SIRT1 activity. Finally, recovery of HIPK2 function downregulated Nox1 expression with rescue of p53 Lys382 acetylation and p53 activity. Together, our findings indicate that Nox1 upregulation may activate SIRT1 and inhibit p53 and that Lys382 is important for p53 proapoptotic function.
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PMID:Nox1 is involved in p53 deacetylation and suppression of its transcriptional activity and apoptosis. 2017 Dec 73


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