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)

Human astrocytoma cells were cultured and inoculated into the rat brain. From the pre-clinical to the terminal state, tumour growth was monitored by in vivo MR imaging and by localized water-suppressed 1H spectroscopy (0.12-0.15 cm3 volumes) and spectroscopic imaging (0.01 cm3 voxels) employing the ACE localization technique. The MR experiments were conducted completely non-invasively, leaving the scalp intact. Brain spectra were obtained, showing distinct resonances for more than five different brain metabolites; they were not contaminated with lipid signals because of the adequate localization. Tumour progression, monitored in a selected volume of interest, was reflected in the corresponding spectra by decreasing intensities for resonances of N-acetyl aspartate and (phospho)creatine and increasing intensities for resonances of choline compounds and lactate. From spectroscopic imaging experiments metabolic heterogeneity could be deduced within the tumorous region. At particular times during tumour development spectra were obtained greatly resembling localized 1H MR spectra obtained from patients with astrocytomas by the use of similar localization methods. This emphasizes the relevance of animal model study for the evaluation of MR spectroscopic investigations in human brain tumour diagnosis and therapy evaluation.
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PMID:Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time. 191 Oct 99

Twenty-eight patients who were previously treated by aggressive surgery and radiation and were diagnosed with supratentorial malignant gliomas received a combination of nimustine hydrochloride; 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cisplatin and etoposide (ACE therapy) as primary treatment. Cisplatin and etoposide were given at doses of 20 and 60 mg/m2/day for 5 days, respectively, ACNU doses 80 mg/m2/day on the first day. Treatment was repeated at 4-week intervals for up to 3 cycles. Seventeen patients (60.7%) complained of nausea. Grade 3 or 4 hematological toxicity occurred in 11 patients (39.3%), and grade 3 or 4 renal toxicity occurred in 2 patients. The percentage of patients who showed complete or partial response was 28.6% (8/28). The median time of tumor progression was 40 weeks, and the median survival time was 146 weeks. There were some long-surviving patients who may have benefited from ACE combination. This study demonstrated the effects of ACE combination in patients with supratentorial malignant gliomas.
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PMID:A phase II study of nimustine hydrochloride, cisplatin, and etoposide combination chemotherapy for supratentorial malignant gliomas. 1121

To detect altered gene expression associated with mouse lung tumor progression, we compared the gene expression profile of lung adenocarcinomas with that of lung adenomas and normal lungs. Autoradiographic analysis showed that among the 588 genes surveyed, 152 genes were detected and the remaining 436 genes did not give any signals. A gene-specific semiquantitative reverse transcription polymerase chain reaction method was used to confirm the expression profile. A total of 29 genes was found to be differentially expressed in mouse lung tumors when compared to normal lungs. The pattern of expression, either underexpression or overexpression, was the same for 10 genes between adenocarcinomas and adenomas. Among them, seven genes were overexpressed, two genes were underexpressed and one gene was lost. Interestingly, 19 genes showed differential expression or increased incidence or difference in level of change between lung adenomas and adenocarcinomas, including Stat1, ADAP, IGFBP-6, PDGF-A, TGF-beta2, Int-3, VEGFR2, BAX, BAG-1, c-Jun, FasL, TRAIL, YB-1, CD31, Cdc42, B-raf, Rab-2, Abi-1, and ACE. These genes can be designated as candidate 'lung tumor progression' (LTP) genes because their expression changes may specifically affect lung tumor progression in mice. Further analyses of these candidate LTP genes may provide new leads for elucidation of lung tumor progression in mice.
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PMID:Differentially expressed genes associated with mouse lung tumor progression. 1217 53

We previously demonstrated that pleiotrophin (PTN the protein, Ptn the gene) highly regulates the levels of expression of the genes encoding the proteins of the renin-angiotensin pathway in mouse aorta. We now demonstrate that the levels of expression of these same genes are significantly regulated in mouse aorta by the PTN family member midkine (MK the protein, Mk the gene); a 3-fold increase in expression of renin, an 82-fold increase in angiotensinogen, a 6-fold decrease in the angiotensin converting enzyme, and a 6.5-fold increase in the angiotensin II type 1 and a 9-fold increase in the angiotensin II type 2 receptor mRNAs were found in Mk-/- mouse aorta in comparison with the wild type (WT, +/+). The results in Mk-/- mice are remarkably similar to those previously reported in Ptn-/- mouse aorta, with the single exception of that the levels of the angiotensinogen gene expression in Ptn-/- mice are equal to those in WT+/+ mouse aorta, and thus, in contrast to Mk gene expression unaffected by levels of Ptn gene expression. The data indicate that MK and PTN share striking but not complete functional redundancy. These data support potentially high levels importance of MK and the MK/PTN developmental gene family in downstream signals initiated by angiotensin II either in development or in the many pathological conditions in which MK expression levels are increased, such as atherosclerosis and many human neoplasms that acquire constitutive endogenous Mk gene expression by mutation during tumor progression and potentially provide a target through the renin-angiotensin pathway to treat advanced malignancies.
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PMID:Midkine, a newly discovered regulator of the renin-angiotensin pathway in mouse aorta: significance of the pleiotrophin/midkine developmental gene family in angiotensin II signaling. 1597 60

Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphism was not found to be linked with H. pylori seropositivity or gastric atrophy. However, among H. pylori seropositive subjects with atrophy, those with the I/D genotype had an increased risk of gastric cancer (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not lower the age at diagnosis of gastric cancer. Confirmation of the association between ACE polymorphisms and development of gastric cancer requires much larger studies, and the biological role also needs to be fully elucidated.
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PMID:The ACE gene polymorphism is associated with the incidence of gastric cancer among H. pylori seropositive subjects with atrophic gastritis. 1643 92

Hepatocellular carcinoma (HCC) is a hypervascular tumor, and tumor progression and prognosis is associated with angiogenesis. Extracellular matrix remodeling and inflammation play important roles in hepatocarcinogenesis. Some ingredients of extracellular matrix such as endostatin and sulfated polysaccharide, some immunomodulatory agents and cox-2 inhibitor suppress the angiogenesis of HCC. Because vasculogenic mimicry is associated with high tumor grade, some differentiation agents are used to inhibit antiagiogenesis. Besides suppressing the proliferation directly, somatostatin inhibits angiogenesis to suppress growth indirectly. Copper chelator prevents copper from functioning as a cofactor in angiogenesis. The renin-angiotensin system is frequently activated in patients with chronic liver diseases. Perindopril, an angiotensin converting enzyme inhibitor, inhibits angiogenesis by reducing vascular endothelial growth factor (VEGF) production. Kinase inhibitors of VEGF and epidermal growth factor receptors are expected to be of benefit for some patients. Following transarterial embolisation and/or resection, antiangiogenic therapy could prevent the recurring and metastasis. Hypoxia enhances the proliferation, suppresses the differentiation and apoptosis, and induces multidrug resistance of HCC. Because antiangiogenic therapies induce hypoxia, it should be borne in mind the side affects of antiangiogenic therapy. Because long-acting antiangiogenent are needed to control cancer, it needs more clinical studies to confirm the drug resistance of antiangiogenetic therapy.
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PMID:New strategy of antiangiogenic therapy for hepatocellular carcinoma. 1899 74

Targeting metabolism represents a possible successful approach to treat cancer. Dichloroacetate (DCA) is a drug known to divert metabolism from anaerobic glycolysis to mitochondrial oxidative phosphorylation by stimulation of PDH. In this study, we investigated the response of two pancreatic cancer cell lines to DCA, in two-dimensional and three-dimension cell cultures, as well as in a mouse model. PANC-1 and BXPC-3 treated with DCA showed a marked decrease in cell proliferation and migration which did not correlate with enhanced apoptosis indicating a cytostatic rather than a cytotoxic effect. Despite PDH activation, DCA treatment resulted in reduced mitochondrial oxygen consumption without affecting glycolysis. Moreover, DCA caused enhancement of ROS production, mtDNA, and of the mitophagy-marker LC3B-II in both cell lines but reduced mitochondrial fusion markers only in BXPC-3. Notably, DCA downregulated the expression of the cancer stem cells markers CD24/CD44/EPCAM only in PANC-1 but inhibited spheroid formation/viability in both cell lines. In a xenograft pancreatic cancer mouse-model DCA treatment resulted in retarding cancer progression. Collectively, our results clearly indicate that the efficacy of DCA in inhibiting cancer growth mechanistically depends on the cell phenotype and on multiple off-target pathways. In this context, the novelty that DCA might affect the cancer stem cell compartment is therapeutically relevant.
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PMID:Dichloroacetate Affects Mitochondrial Function and Stemness-Associated Properties in Pancreatic Cancer Cell Lines. 3110 89

Obesity is a complex disease and a global epidemic. It is a risk factor for other chronic diseases including breast cancer, especially in women after menopause. Diverse etiologies underlie the relationship between obesity and breast cancer. Adipose tissue is in part responsible for these interactions. In obesity, adipose tissue undergoes several metabolic dysregulations resulting in the secretion of many pro-inflammatory cytokines, growth factors, and hormones which in turn, can promote tumor microenvironment (TME) formation and cancer progression within the breast tissue. Angiotensin II (Ang II) is a well-known hypertensive hormone produced systemically and locally by the renin-angiotensin system (RAS). Activation of this system in obesity is a potential contributor to local and systemic inflammation in breast adipose tissue. Ang II actions are primarily mediated through binding to its two receptors, type 1 (AT1R) and type 2 (AT2R). RAS inhibitors include angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) which are currently prescribed as safe antihypertensive therapies. Recent studies have explored the potential use of ACE-I and ARBs in breast cancer patients as anti-tumor agents. Therefore, it is vital to understand the role of RAS in breast cancer and identify mechanisms of Ang II and RAS inhibitors in the TME and in obesity and breast cancer crosstalk. In this review, we performed a detailed analysis and discussed mechanisms of Ang II-AT1R interactions in breast cancer with emphasis on obesity-associated breast cancer. We further summarized recent in vitro, in vivo and human studies that used ACE-I/ARB interventions to improve breast cancer outcomes.
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PMID:Mechanisms linking the renin-angiotensin system, obesity, and breast cancer. 3152 26

The ongoing coronavirus disease 2019 (COVID-19) pandemic has affected millions worldwide and has been found to cause severe disease in patients with underlying comorbidities. In patients with known malignancies, in addition to constraints in routine healthcare, the risk of being susceptible to developing severe forms of the disease is of grave concern. While follow-up studies on survivors of the severe acute respiratory syndrome (SARS) 2003 outbreak revealed increased susceptibility to infections, tumours and cardiovascular abnormalities, recent studies implicating angiopoietin 2 in induction of inflammatory intussusceptive angiogenesis and diffuse alveolar damage in COVID-19 patients raises the possibility of progression of carcinogenetic processes in patients with known malignancies. Angiotensin converting enzyme-2 (ACE-2) mediated cellular entry of SARS-Cov2 leads to receptor shedding of ACE-2 and disrupts the renin angiotensin aldosterone axis (RAAS). This augments the pro-inflammatory and proliferative effects of RAAS, while attenuating the anti-inflammatory and anti-proliferative angiotensin 1-7 /Mas pathway. Angiopoietin-2, a molecule responsible for angiogenesis and cancer progression which corelates with tumour load in certain cancers, is upregulated by angiotensin 2-AT1 Receptor axis. Tumour microenvironment-comprising of various cells, blood vessels and extra cellular matrix which express the RAAS peptides-plays a key role in cancer initiation, progression and metastasis. Angiotensin 2 induces the formation of a desmoplastic environment, favouring cancer cell growth. ACE-2 downregulation causes bradykinin accumulation which may exert its proliferative action via mitogen activated protein kinase pathways which has established roles in cancers of breast and kidney. In addition to cytokine storm causing organ damage, acute inflammation in COVID-19 may also cause epithelial mesenchymal transition and heat shock protein 27 phosphorylation, both of which are key mediators in cancer signalling pathways. We hypothesise that SARS-Cov2, by impacting the RAAS and immune system, has the potential to cause tumour cell proliferation, apoptosis evasion and metastasis, thereby increasing the possibility of cancer progression in patients with known malignancies.
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PMID:Cancer progression in COVID-19: integrating the roles of renin angiotensin aldosterone system, angiopoietin-2, heat shock protein-27 and epithelial mesenchymal transition. 3308 49