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

Myoglobin is a multifunctional heme protein that is thought to be expressed exclusively in myocytes. Its importance in both oxygen transport and free radical scavenging has been extensively characterized. We hypothesized that solid tumors could take advantage of proteins such as myoglobin to cope with hypoxic conditions and to control the metabolism of reactive oxygen and nitrogen species. We therefore sought to establish whether myoglobin might be expressed and functionally regulated in epithelial tumors that are known to face hypoxia and oxidative stress during disease progression. We analyzed the expression of myoglobin in human epithelial cancers at both transcriptional and protein levels; moreover, we investigated the expression levels of myoglobin in cancer cell lines subjected to different conditions, including hypoxia, oxidative stress, and mitogenic stimuli. We provide evidence that human epithelial tumors, including breast, lung, ovary, and colon carcinomas, express high levels of myoglobin from the earliest stages of disease development. In human cancer cells, myoglobin is induced by a variety of signals associated with tumor progression, including mitogenic stimuli, oxidative stress, and hypoxia. This study provides evidence that myoglobin, previously thought to be restricted to myocytes, is expressed at high levels by human carcinoma cells. We suggest that myoglobin expression is part of a cellular program aimed at coping with changed metabolic and environmental conditions associated with neoplastic growth.
 ...
PMID:Expression and functional regulation of myoglobin in epithelial cancers. 1954 31

BNIP3 belongs to the Bcl-2 protein family that regulates programmed cell death. It is the only known pro-apoptotic protein expressed during hypoxia and this effect is determined by the HIF-1 responsive element in the bnip3 promoter. However, there is evidence that hypoxia is not a sufficient factor to activate BNIP3; possible cell death dependent on this protein occurs as a result of secondary effects of oxygen deprivation, such as acidosis. BNIP3 expression is also regulated by other factors, such as E2F-1, NF-kappaB, and Rb during hypoxia and nitrogen oxide during normoxia. Posttranslational modifications also seem to be essential for BNIP3 activity, but their actual significance is still unclear. Phosphorylation of BNIP3 by PKC promotes its accumulation under hypoxic conditions, but phosphorylation by CK2 can accelerate its degradation. In turn, glycosylation and interactions with anti-apoptotic Bcl-2 proteins suppress BNIP3 activity. Our knowledge about the role of BNIP3 protein in tumor progression is incomplete. It seems to be dependent on the stage of tumor progression. Tumor cells evolved multiple mechanisms of silencing BNIP3 expression or activity and promoter methylation is one of the most frequently observed among them
 ...
PMID:[BNIP3 as an atypical representative of the Bcl-2 protein family. Part 2: Regulation of the expression and activity of BNIP3 protein and its role in tumorigenesis]. 1974 28

Platinum compounds are among the most used DNA-damaging anticancer drugs, however they can also be tailored to target biological substrates different from DNA, for instance enzymes involved in cancer progression. We recently reported that some platinum complexes with three labile ligands inhibit matrix metalloproteinase activity in a selective way. We have now extended the investigation to a series of platinum complexes having three chlorido or one chlorido and a dimethylmalonato leaving ligands. All compounds are strong inhibitors of MMP-3 by a noncompetitive mechanism, while platinum drugs in clinical use are not. Structural investigations reveal that the platinum substrate only loses two labile ligands, which are replaced by an imidazole nitrogen of His224 and a hydroxyl group, while it retains one chlorido ligand. A chlorido and a hydroxyl group are also present in the zinc complex inhibitor of carboxypeptidase A, whose active site has strong analogies with that of MMP-3.
 ...
PMID:Mechanistic insight into the inhibition of matrix metalloproteinases by platinum substrates. 1975 21

Bisphosphonates are expected to be effective at preventing tumor metastasis to bone tissue. Since protein kinase C (PKC) plays a crucial role in cancer progression, we examined the effect of bisphosphonates on PKC expression to clarify the mechanism behind the inhibition of the bone metastasis of prostate cancer by bisphosphonates. We found that pamidronate inhibits PKC protein expression and PKC activity in prostate cancer PC-3 cells. PKC protein expression was markedly reduced by treatment with 100 microM of pamidronate. The inhibitory effect of PKC expression by pamidronate was specific for PKCalpha and PKCzeta. Nitrogen-containing bisphosphonates are known to inhibit the mevalonate pathway, but the effect of pamidronate on PKC expression was not due to the inhibition of this pathway. Urokinase-type plasminogen activator (uPA) is one of the critical proteins in tumor metastasis and decreased in bisphosphonate-treated PC-3 cells. We also showed that uPA expression was suppressed by PKC inhibitors (calphostin C and staurosporine) and induced by a PKC activator (PMA) in PC-3 cells, suggesting that the inhibition of uPA by bisphosphonates is involved in PKC inhibition. This is the first finding that bisphosphonates suppress PKC expression in cancer cells. These results strongly suggest that one of the mechanisms behind the inhibitory effect of bisphosphonates on tumor bone metastasis is mediated by PKC inhibition.
 ...
PMID:Protein kinase C is inhibited by bisphosphonates in prostate cancer PC-3 cells. 1990 68

Chronic infection and inflammation contribute to a substantial part of environmental carcinogenesis. Recently, it has been estimated that chronic inflammation accounts for approximately 25% of cancer cases. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species, which are generated from inflammatory and epithelial cells, may play an important role in carcinogenesis by causing DNA damage. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. In an earlier publication, our group reported the results of an immunohistochemical analysis of animals infected with the liver fluke Opisthorchis viverrini and demonstrated for the first time that 8-nitroguanine was formed at the sites of carcinogenesis. This DNA lesion was found to accumulate in the carcinogenic process in clinical specimens of cancer-prone inflammatory diseases caused by various pathogens, including human papillomavirus and Epstein-Barr virus. Moreover, strong 8-nitroguanine formation in tumor tissues was closely associated with a poor prognosis. On the basis of these findings, 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related carcinogenesis and the prognosis of cancer patients. In this review, the significance of 8-nitroguanine formation in inflammation-related carcinogenesis and tumor progression will be discussed.
 ...
PMID:Formation of 8-nitroguanine, a nitrative DNA lesion, in inflammation-related carcinogenesis and its significance. 1992 94

Patients with ulcerative colitis and Crohn's disease are at increased risk of developing intestinal cancers via mechanisms that remain incompletely understood. However, chronic inflammation and repeated events of inflammatory relapse in inflammatory bowel disease (IBD) expose these patients to a number of signals known to have tumorigenic effects including persistent activation of the nuclear factor-kappaB and cyclooxygenase-2/prostaglandin pathways, release of proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6, and enhanced local levels of reactive oxygen and nitrogen species. These inflammatory signals can contribute to carcinogenesis via 3 major processes: 1) by increasing oxidative stress, which promotes DNA mutagenesis thus contributing to tumor initiation; 2) by activating prosurvival and antiapoptotic pathways in epithelial cells, thereby contributing to tumor promotion; and 3) by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of tumor cells, thus supporting tumor progression and metastasis. The present review integrates clinical and basic research observations in an attempt to provide a comprehensive understanding of how inflammatory processes may contribute to intestinal cancer development in IBD patients.
 ...
PMID:Mechanisms by which inflammation may increase intestinal cancer risk in inflammatory bowel disease. 2015 48

We have previously shown that ARG2 expression was increased in most malignant thyroid tumors, but absent in benign lesions and normal tissues. Small interfering RNA knockdown was used to investigate the role of ARG2 in a thyroid carcinoma cell line. ARG2 knockdown decreased eNOS expression as well as the expression of eNOS-related genes (p21, Akt1, HIF-1, VEGF, and CAV1). ARG2 silencing changed tumor properties of thyroid cancer cells promoting apoptosis and reduced expression of cell proliferation markers. These results, coupled with enhanced nitric oxide production and elevated reactive oxygen species (ROS) levels, account for the altered intracellular redox environment. Genes related to either production (DUOX1 and NOX4) or catabolism (SODs) of ROS and reactive nitrogen species were negatively modulated by ARG2 knockdown. Additionally, a positive correlation of ARG2 with eNOS and related genes was investigated in thyroid tumors, further substantiating our in vitro findings. Our results suggest that ARG2 and eNOS may work in a coordinated manner and the underlying mechanism might be of major significance for thyroid tumorigenesis and/or tumor progression pathways. Fine modulation of ARG2, eNOS, and related genes may represent a potential source for targeted therapy of several cancer types.
 ...
PMID:Arginase 2 and nitric oxide synthase: Pathways associated with the pathogenesis of thyroid tumors. 2054 7

Malignant melanoma is characterized by a rapid progression, metastasis to distant organs, and resistance to chemo- and radiotherapy. Well-defined immunogenic capacities of melanoma cells should allow a successful application of different immunotherapeutic strategies. However, the overall results of immunotherapeutic clinical studies are not satisfactory. These paradoxical observations are supposed to be due to the profound immunosuppression mediated by different mechanisms dealing with alterations in tumor and surrounding stroma cells. Melanoma microenvironment has been characterized by a remarkable accumulation of highly immunosuppressive regulatory leucocytes, in particular, myeloid-derived suppressor cells (MDSCs). Their migration, retention and high activity in the tumor lesions have been demonstrated to be induced by chronic inflammatory conditions developing in the tumor microenvironment and characterized by the long-term secretion of various inflammatory mediators (cytokines, chemokines, growth factors, reactive oxygen and nitrogen species, prostaglandins etc.) leading to further cancer progression. Here, we discuss the role of chronic inflammation in the recruitment and activation of MDSCs in melanoma lesions as well as therapeutic approaches of MDSC targeting to overcome tumor immunosuppressive microenvironment induced by chronic inflammation and enhance the efficiency of melanoma immunotherapies.
 ...
PMID:Melanoma-induced immunosuppression and its neutralization. 2234 15

Nutritional supplementation with some amino acids may influence host's responses and also certain mechanism involved in tumor progression. It is known that exercise influences body weight and muscle composition. Previous findings from our group have shown that leucine has beneficial effects on protein composition in cachectic rat model as the Walker 256 tumor. The main purpose of this study was to analyze the effects of light exercise and leucine and/or glutamine-rich diet in body composition and skeletal muscle protein synthesis and degradation in young tumor-bearing rats. Walker tumor-bearing rats were subjected to light aerobic exercise (swimming 30 min/day) and fed a leucine-rich (3%) and/or glutamine-rich (4%) diet for 10 days and compared to healthy young rats. The carcasses were analyzed as total water and fat body content and lean body mass. The gastrocnemious muscles were isolated and used for determination of total protein synthesis and degradation. The chemical body composition changed with tumor growth, increasing body water and reducing body fat content and total body nitrogen. After tumor growth, the muscle protein metabolism was impaired, showing that the muscle protein synthesis was also reduced and the protein degradation process was increased in the gastrocnemius muscle of exercised rats. Although short-term exercise (10 days) alone did not produce beneficial effects that would reduce tumor damage, host protein metabolism was improved when exercise was combined with a leucine-rich diet. Only total carcass nitrogen and protein were recovered by a glutamine-rich diet. Exercise, in combination with an amino acid-rich diet, in particular, leucine, had effects beyond reducing tumoral weight such as improving protein turnover and carcass nitrogen content in the tumor-bearing host.
 ...
PMID:Light aerobic physical exercise in combination with leucine and/or glutamine-rich diet can improve the body composition and muscle protein metabolism in young tumor-bearing rats. 2246 Mar 63

Tumor progression has been demonstrated to be supported by chronic inflammatory conditions developed in the tumor microenvironment and characterized by the long-term secretion of various inflammatory soluble factors (including cytokines, chemokines, growth factors, reactive oxygen and nitrogen species, prostaglandins etc.) and strong leukocyte infiltration. Among leukocytes infiltrating tumors, myeloid-derived suppressor cells (MDSCs) represent one of the most important players mediating immunosuppression. These cells may not only strongly inhibit an anti-tumor immune reactions mediated by T cells but also directly stimulate tumorigenesis, tumor growth and metastasis by enhancing neoangiogenesis and creating a suitable environment for the metastatic formation. This review provides an overview of interactions between MDSCs and tumor cells leading to MDSC generation, activation and migration to the tumor site, where they can strongly enhance tumor progression. Better understanding of the MDSC-tumor interplay is critical for the development of new strategies of tumor immunotherapy.
...
PMID:Tumor microenvironment and myeloid-derived suppressor cells. 2324 72


<< Previous 1 2 3 4 5 6 7 8 Next >>