Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the recent advances in the immunological surveillance system, an understanding of the role of host immunity has become essential to the management of carcinogenesis, tumor proliferation, recurrence and metastasis. Although it is important to continue chemical and surgical treatment of cancer, support of the anti-tumor immune system of the host should also be considered. Long term remission has been reported in leukemia by treating with BCG after chemotherapy whereas surgical treatment is usually more effective in preventing cancer recurrence in digestive organ cancer. The first step is extirpating the tumor as thoroughly as possible and the second step is chemo-immunotherapy. Cancer immunity, however weak, constitutes the basis for other treatments in selectively attacking cancer cells remaining after surgery, chemotherapy or irradiation. Immunotherapy should thus not replace chemotherapy or radiotherapy, but these methods should be employed in combination to attain more favorable results.
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PMID:Cancer immunotherapy with surgery. 14 59

The central theme of this communication is the recognition of an immunodiagnostic potential in a herpes virus antigen, the molecular interrelationship of which with cervical tumor cells is described. In addition to the productive infection caused by herpes simplex virus type 2 (HSV-2) we are confronted by latency and, as suggested by recent studies, by cancer. These different types of virus-host cell interactions are discussed at the host, as well as at the cellular level. A defined level of molecular interaction between host and viral gene products must exist if the virus is to co-exist with the host, as is the case in latency and carcinogenesis. The molecular interpretations posit the presence, in the squamous cervical tumor cells, of a product of the expression of the viral genome that has immunodiagnostic potential. The antigen designated AG-4 fulfills these predictions and appears to have immunodiagnostic potential. AG-4 is present in cervical tumor biopsies, but not in normal cervical tissue. It is a structural component of the HSV-2 virion that, in tissue cultures infected with HSV-2, is synthesized preferentially under conditions that prevent the normal replication of the virus. In view of its structural nature it is most probably virus-coded. AG-4 antibody identified in complement fixation assays with antigen prepared in tissue culture, disappears following successful tumor removal and reappears during cancer recurrence. This antibody also potentially identifies those patients with cervical atypia that are at high risk of neoplastic progression. The clinical benefits of the assay are evident.
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PMID:Immunodiagnostic potential of a virus-coded, tumor-associated antigen (AG-4) in cervical cancer. 19 36

After defining chemoprevention a description is given of the phases of differentiation in normal epithelial cells and the features of proliferation in neoplasias developing in this epithelium. The latest studies on carcinogenesis indicate various types of prevention with which one can alter this transformation process. Epidemiological studies have shown that subjects with low serum levels of Vit-A or Beta carotenoids are at high risk of developing epithelial cancer. Three main categories of agents inducing cell transformation are described: a) physiological induction agents; b) non physiological induction agents; c) cytotoxic drugs. In regard to clinical use, some studies have focussed on the importance of Vit-A in chemoprevention of risk conditions (pre-cancerous lesions) and in prevention of cancer recurrence. The authors point out the increasing interest in the use of retinoids in the chemoprevention of head and neck cancer and report some personal clinical experience.
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PMID:[Biological aspects and perspectives applicable to the chemoprevention of cancer of the upper respiratory-digestive tract]. 220 23

Using colonic cancer induced by DMH as experimental model, carcinogenic rate in the rats with or without partial colectomy was compared in order to study the etiology of the local recurrence of large bowel cancer after radical resection and observe the influence of operative injury on carcinogenesis. Sixty five male Wistar rats were divided into two groups: 48 with a partial colectomy (group 1) and 17 controls (group 2). All were given subcutaneous injection of DMH 20 mg/kg weekly for twenty weeks. Then, some rats were killed on scheduled time, the others were sacrificed in the 29th week. The results showed that carcinogenic rate was 87.5% and 58.8% in groups 1 and 2 (P less than 0.05). The tumor number in anastomotic site in group 1 (57.1%) was much higher than that at corresponding site in group 2 (28.6%) (P less than 0.05). It is suggested that the trauma itself be one of the promoting factors for cancer recurrence in addition to implantation during operation, residual tumor, etc. Large bowel cancer induced by DMH in rats may be used as an experimental model in studying the same cancer in the human being. Furthermore, after having given DMH, large bowel cancer incidence of the rats in different intervals is described.
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PMID:[Colonic cancer induced by 1,2-dimethylhydrazine (DMH) in rats after partial colectomy]. 283 58

Increased fruit and vegetable consumption is associated with decreased risk of a number of cancers of epithelial origin, including esophageal cancer. Dietary administration of lyophilized black raspberries (LBRs) has significantly inhibited chemically induced oral, esophageal, and colon carcinogenesis in animal models. Likewise, berry extracts added to cell cultures significantly inhibited cancer-associated processes. Positive results in preclinical studies have supported further investigation of berries and berry extracts in high-risk human cohorts, including patients with existing premalignancy or patients at risk for cancer recurrence. We are currently conducting a 6-mo chemopreventive pilot study administering 32 or 45 g (female and male, respectively) of LBRs to patients with Barrett's esophagus (BE), a premalignant esophageal condition in which the normal stratified squamous epithelium changes to a metaplastic columnar-lined epithelium. BE's importance lies in the fact that it confers a 30- to 40-fold increased risk for the development of esophageal adenocarcinoma, a rapidly increasing and extremely deadly malignancy. This is a report on interim findings from 10 patients. To date, the results support that daily consumption of LBRs promotes reductions in the urinary excretion of two markers of oxidative stress, 8-epi-prostaglandin F2alpha (8-Iso-PGF2) and, to a lesser more-variable extent, 8-hydroxy-2'-deoxyguanosine (8-OHdG), among patients with BE.
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PMID:Transitioning from preclinical to clinical chemopreventive assessments of lyophilized black raspberries: interim results show berries modulate markers of oxidative stress in Barrett's esophagus patients. 1680 Jul 81

The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P < 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.
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PMID:Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence. 1700 85

Multiple primary cancers including small intestinal tumors are rare. We describe the first curative resection case of metachronous triple early cancers involving the jejunum as well as the stomach and esophagus. The patient had undergone total gastrectomy for a gastric adenocarcinoma and subsequent esophagectomy for an esophageal squamous cell carcinoma. A jejunal adenocarcinoma, the third primary, occurred at the blind stump of the jejunal limb of a Roux-en-Y esophagojejunostomy reconstructed previously. This tumor was removed by partial resection of the limb with the preservation of the esophagojejunostomy. The patient died from complications of acute pancreatitis 3 years after the last operation, without overt clinical signs of cancer recurrence. Immunohistochemistry of the specimen showed the increased expression of p53 and cyclin D1 proteins in all three cancers, suggesting their involvement in metachronous carcinogenesis in this case. Early diagnosis of each cancer was made possible by regular endoscopic follow-up and favorable anatomical location of each tumor, which were considered to allow less invasive surgery as well as to contribute to the favorable outcome. This case suggests the importance of regular surveillance for metachronous carcinogenesis, especially when the preceding cancers carry genetic abnormalities that may potentially increase the risk for subsequent carcinogenesis.
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PMID:Primary jejunal adenocarcinoma as part of multiple primary cancers of the digestive tract. 1839 95

Epigenetic alterations play an important role in carcinogenesis. Recent studies suggested that global histone modifications are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone H3 lysine 4 mono-methyl (H3K4me1), -di-methyl (H3K4me2) and -trimethyl (H3K4me3) patterns in renal cell carcinoma (RCC) using a tissue microarray with 193 RCC (including 142 clear cell, 31 papillary, 10 chromophobe and 10 sarcomatoid RCC) and 10 oncocytoma specimens: H3K4me3 staining was more intense in papillary RCC, whereas H3K4me1 and H3K4me2 were similar in the diverse RCC subtypes. H3K4me2 and H3K4me3 levels were increased in oncocytoma. H3K4me1-3 levels were inversely correlated with Fuhrman grading, pT stage, lymph node involvement and distant metastasis. Progression-free survival and cancer-specific survival were shorter in patients with low levels of H3K4me1-3 in the univariate analysis, but we did not observe a significant correlation of a single modification in a multivariate model, which also included the established prognostic parameters TNM-stage and Fuhrman grade. In comparison, the H3K4me score, which combined staining levels of the H3K4 modifications, was an independent predictor of RCC progression-free survival. Our study on H3K4 methylation supports the concept of global histone modifications as potential cancer prognosis markers.
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PMID:Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. 2016 70

Curcumin (diferuloylmethane), which has no discernible toxicity, inhibits initiation, promotion and progression of carcinogenesis. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces an incomplete response resulting in survival of cells (chemo-surviving cells) that may lead to cancer recurrence. The present investigation was, therefore, undertaken to examine whether addition of curcumin to FOLFOX is a superior therapeutic strategy for chemo-surviving cells. Forty-eight-hour treatment of colon cancer HCT-116 and HT-29 cells with FOLFOX resulted in 60-70% survival, accompanied by a marked activation of insulin like growth factor-1 receptor (IGF-1R) and minor to moderate increase in epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2) as well as v-akt murine thymoma viral oncogene homolog 1 (AKT), cyclooxygenase-2 (COX-2) and cyclin-D1. However, inclusion of curcumin to continued FOLFOX treatment for another 48 h greatly reduced the survival of these cells, accompanied by a concomitant reduction in activation of EGFR, HER-2, IGF-1R and AKT, as well as expression of COX-2 and cyclin-D1. More importantly, EGFR tyrosine kinase inhibitor gefitinib or attenuation of IGF-1R expression by the corresponding si-RNA caused a 30-60% growth inhibition of chemo-surviving HCT-116 cells. However, curcumin alone was found to be more effective than both gefitinib and IGF-1R si-RNA mediated growth inhibition of chemo-surviving HCT-116 cells and addition of FOLFOX to curcumin did not increase the growth inhibitory effect of curcumin. Our data suggest that inclusion of curcumin in conventional chemotherapeutic regimens could be an effective strategy to prevent the emergence of chemoresistant colon cancer cells.
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PMID:Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. 2033 35

Cancer stem cells (CSCs) play an important role in carcinogenesis, resistance to treatment and may lead to cancer recurrence and metastasis. However, the molecular mechanism of CSC involved in these events needs to be further elucidated. In this study, CD133(+) colon cancer cells were cultured, which showed CSC properties both in vitro and in vivo from metastatic tissue. Upstream molecules in Akt and mitogen-activated protein kinase (MAPK) pathways were preferentially expressed in these CD133(+) cells, as revealed by a global gene chip. The kinase activities of Akt and extracellular signal-regulated kinase (Erk)1/2 were also significantly upregulated in CD133(+) cells. In addition, the clonogenic growth of CD133(+) cell was reduced greatly by inhibiting the activity of Akt and Erk1/2. The results revealed the Akt and MAPK pathways were involved in the tumorigenesis of CD133(+) colon cancer cells, suggesting that molecules in these two pathways might be potential targets in the future therapy.
Carcinogenesis 2010 Aug
PMID:Activation of Akt and MAPK pathways enhances the tumorigenicity of CD133+ primary colon cancer cells. 2053 May 54


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