Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new human esophageal cancer cell line (YES-1) was established from a subcutaneous tumor implanted into nude mice, which had been transplanted from a surgical specimen obtained 50-year-old Japanese male patient. This cell line has been maintained for 33 months through 94 passages with stable growth. YES-1 cells are mainly polygonal-to-spindle shaped, have eosinophilic cytoplasm and oval-to-round nuclei with some prominent nucleoli. There are also some cells having clear cytoplasm and round nuclei with prominent nucleoli. The cells proliferate in a pavement-like cell arrangement and show a lack of contact inhibition. The doubling time at the 33rd passage was 35.2 hours. YES-1 cells produce carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC antigen) and tissue polypeptide antigen (TPA) as tumor markers. Chromosome study have shown that the chromosome number ranges from 47 to 54 with a mode of 51. Tumorigenicity has been identified by the development of tumors after the subcutaneous injection of YES-1 cells into nude mice, which were found to be similar to the original tumor on histological examination. Thus, these findings indicate that the YES-1 cell line is available as a new human esophageal cancer cell line which should be useful for various studies.
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PMID:Establishment and characterization of a new human esophageal cancer cell line (YES-1). 181 37

We reported that human esophageal cancer cell lines (ECC) (YES-1, -2, -3, -4, -5, and -6) produced interleukin-6 (IL-6). We, therefore, investigated the growth effects ([3H]thymidine uptake assay and direct cell count) of IL-6 on these ECC. IL-6 receptor (R) and GP-130 mRNA were detected in all the ECC, using reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and IL-6R was detected in one (YES-3) by immunohistochemical staining. IL-6, anti-IL-6 monoclonal antibody (mAb), or anti-IL-6R mAb caused no reproducible enhancement or suppression of [3H]thymidine uptake by all six ECC. Direct cell count also revealed that the growth enhancement or suppression by IL-6, anti-IL-6 mAb, or anti-IL-6R mAb was relatively small. Particularly, there was no significant sensitivity of YES-3 cells, which definitely produce IL-6 and express IL-6R for IL-6, anti-IL-6 mAb, or anti-IL6R mAb. These results suggest that some esophageal cancers may produce IL-6 and express IL-6R. However, no major interactions between IL-6 and the growth of human esophageal cancer cell lines were detected in this study.
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PMID:The influence of interleukin-6 on the growth of human esophageal cancer cell lines. 897 1

Our previous study demonstrated that the herbal medicine, Oren-to, had antitumor effects on esophageal cancer cells (ECCs) in vitro. The purpose of this study was to examine which of the seven constituents of Oren-to had antitumor effects on esophageal cancer cells. MTT assay showed that, of the seven constituents, only the aqueous extract of Coptidis Rhizoma had potent inhibitory effect on the proliferation of two types of ECC lines, YES-3 and YES-4. In addition, the proliferation of all six types of ECC lines (YES-1 to YES-6) was inhibited in a dose-dependent manner (P<0.001 for all), when co-cultured at each concentration of Coptidis Rhizoma for 72 h. The ID50 of Coptidis Rhizoma for YES-1 to YES-6 was 2.2 microg/ml, 3.0 microg/ml, 0.25 microg/ml, 2.8 microg/ml, 2.5 microg/ml, and 0.5 microg/ml, respectively, berberine, one of protoberberine components of Coptidis Rhizoma, showed potent antitumor effects on all six types of ECC lines as well as Coptidis Rhizoma. In addition, the ID50 of berberine showed a positive correlation with that of Coptidis Rhizoma in six types of ECC lines examined (r2 = 0.763, P = 0.023). Cell cycle analysis of Coptidis Rhizoma-treated cancer cells showed the accumulation of cells in the G0/G1 phase and relative decrease of the S phase. These results support the possibility that the use of Coptidis Rhizoma containing abundant berberine may be useful as one of alternative therapies for esophageal cancers.
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PMID:Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. 1068 May 88

Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.
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PMID:Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6. 1094 May 6

Esophageal cancer is one of the most lethal human tumors, characterized by relative chemoresistance and poor prognosis. Researchers have been seeking for multimodality to improve its outcome of therapy. PUMA (p53 upregulated modulator of apoptosis) is a potent proapoptotic molecule that is rapidly induced in cells following DNA damage and is required for p53-induced apoptosis. We evaluated the therapeutic potential of PUMA adenovirus against esophageal cancer cell lines (KYSE-150, KYSE-410, KYSE-510 and YES-2). Infection with Ad-PUMA (PUMA Adenovirus) resulted in the more powerful cytotoxicity in these cell lines compared with Ad-p53. Furthermore, we assessed the efficacy of a combined treatment with Ad-PUMA and anticancer drug (cisplatin, paclitaxel, 5-fluorouracil, respectively) for these cells and found PUMA significantly increased the chemosensitivity of esophageal cancer cells, which may result from more abundant apoptosis induction. Interestingly, Ad-PUMA was found to be more efficient than Ad-p53 in inhibiting cell growth and enhancing the chemosensitivity of esophageal cancer cell lines irrespective of the p53 status. These results suggest that Ad-PUMA is a potent cytotoxic agent and could be a promising alternative in the cancer gene therapy in combination with chemotherapeutic agents.
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PMID:Administration of PUMA adenovirus increases the sensitivity of esophageal cancer cells to anticancer drugs. 1648 41

The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2 cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer.
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PMID:Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo. 1946 49

Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents to control esophageal cancer. Herein, we investigated that the effect and mechanism of tetrandrine (TET) in the human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP. The human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP was isolated by stepwise selection in increasing concentrations of cisplatin. The CCK-8 method was carried out to measure the cell viability when cells were exposed to TET with or without cisplatin, and the IC50 and resistance index (RI) of cisplatin was then calculated. Real-time RT-PCR and western blotting were used to detect the mRNA and protein expression of multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), respectively. Flow cytometry was adopted to determine CMFDA efflux and cell apoptosis, respectively. The resulting cell line YES-2/DDP was 16.4-fold resistant to cisplatin, the cytotoxicity of cisplatin to YES-2/DDP cells was enhanced by TET in a dose-dependent manner. Further, it was found that the expression of MDR1 and BCRP was similar in different treated cells. In contrast, the expression of MRP1 was markedly increased in YES-2/DDP cells, which was dose-dependently decreased by TET. In agreement with the results, MRP1 activity was also reversed by TET. In conclusion, TET possesses a reversal effect on drug resistance in YES-2/DDP cells through downregulation of MRP1, and has the potential to be an adjunct to chemotherapy for esophageal cancer.
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PMID:Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1. 2294 7

Cancer stem cells (CSCs) appear to resist chemo-radiotherapy and initiate tumor recurrence in patients. Isolation and further characterization of this subpopulation is important for targeting CSCs. Flow cytometry using Aldefluor, a fluorescent substrate of aldehyde dehydrogenase, has been used to isolate CSCs from various cancer cell lines. However, new techniques are needed to locate and identify CSCs in culture for live-cell analyses such as fluorescence microscopy without introducing artifacts during cell sorting and to observe CSC and non-CSC interactions. Previously, we characterized a distinct CSC subpopulation within human esophageal cancer cell lines (ESCC). In this study we introduce the attached-cell Aldefluor method (ACAM) to detect CSCs in ESCC cell lines (KY-5, KY-10, TE-1, TE-8, YES-1, YES-2). To validate this technique, we isolated CSCs from the YES-2 parental line using standard Aldefluor flow cytometry to create a cell line enriched in CSCs (YES-2CSC). This line showed significantly greater ACAM staining and higher CD44 levels than YES-2. ACAM also showed significantly higher ALDH activity in YES-2CSC than in YES-2S, a cell line that has a diminished CSC subpopulation after having survived treatment with curcumin. ACAM stained cells within tumorspheres made from the CSC-enriched line but not differentiating cells from the tumorspheres. This study also demonstrates a new method for generating and growing tumorspheres without the growth factor supplements normally used in medium to form tumorspheres. ACAM should be evaluated using other cancer cell lines to further substantiate its effectiveness and to characterize CSCs in culture through various imaging techniques.
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PMID:A new method for identifying stem-like cells in esophageal cancer cell lines. 2398 18

Targeting genetic alterations of oncogenes by molecular-targeted agents (MTA) is an effective approach for treating cancer. However, there are still no clinical MTA options for many cancers, including esophageal cancer. We used a short hairpin RNA library to screen for a new oncogene in the esophageal cancer cell line KYSE70 and identified YES proto-oncogene 1 (YES1) as having a significant impact on tumor growth. An analysis of clinical samples showed that YES1 gene amplification existed not only in esophageal cancer but also in lung, head and neck, bladder, and other cancers, indicating that YES1 would be an attractive target for a cancer drug. Because there is no effective YES1 inhibitor so far, we generated a YES1 kinase inhibitor, CH6953755. YES1 kinase inhibition by CH6953755 led to antitumor activity against YES1-amplified cancers in vitro and in vivo. Yes-associated protein 1 (YAP1) played a role downstream of YES1 and contributed to the growth of YES1-amplified cancers. YES1 regulated YAP1 transcription activity by controlling its nuclear translocation and serine phosphorylation. These findings indicate that the regulation of YAP1 by YES1 plays an important role in YES1-amplified cancers and that CH6953755 has therapeutic potential in such cancers. SIGNIFICANCE: These findings identify the SRC family kinase YES1 as a targetable oncogene in esophageal cancer and describe a new inhibitor for YES1 that has potential for clinical utility.See related commentary by Rai, p. 5702.
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PMID:YES1 Is a Targetable Oncogene in Cancers Harboring YES1 Gene Amplification. 3177 72