FMSP-Nanoparticles Induced Cell Death on Human Breast Adenocarcinoma Cell Line (MCF-7 Cells: Morphometric Analysis

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Firdos Alam Khan

2018-05-01

Full Text Available Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7. We tested different concentrations (1.25, 12.5 and 50 µg/mL of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.

Ajwa Date (Phoenix dactylifera L. Extract Inhibits Human Breast Adenocarcinoma (MCF7 Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest.

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Fazal Khan

Full Text Available Phoenix dactylifera L (Date palm is a native plant of the Kingdom of Saudi Arabia (KSA and other Middle Eastern countries. Ajwa date has been described in the traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remains to be scientifically validated. Herein, we evaluated the anticancer effects of the Methanolic Extract of Ajwa Date (MEAD on human breast adenocarcinoma (MCF7 cells in vitro.MCF7 cells were treated with various concentrations (5, 10, 15, 20 and 25 mg/ml of MEAD for 24, 48 and 72 h and changes in cell morphology, cell cycle, apoptosis related protein and gene expression were studied.Phase contrast microscopy showed various morphological changes such as cell shrinkage, vacuolation, blebbing and fragmentation. MTT (2-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay demonstrated statistically significant dose-dependent inhibitions of MCF7 cell proliferation from 35% to 95%. Annexin V-FITC and TUNEL assays showed positive staining for apoptosis of MCF7 cells treated with MEAD (15 mg and 25 mg for 48 h. Flow cytometric analyses of MCF7 cells with MEAD (15 mg/ml and 20 mg/ml for 24 h demonstrated cell cycle arrest at 'S' phase; increased p53, Bax protein expression; caspase 3activation and decreased the mitochondrial membrane potential (MMP. Quantitative real time PCR (qRT-PCR analysis showed up-regulation of p53, Bax, Fas, and FasL and down-regulation of Bcl-2.MEAD inhibited MCF7 cells in vitro by the inducing cell cycle arrest and apoptosis. Our results indicate the anticancer effects of Ajwa dates, which therefore may be used as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer.

Appendiceal goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid are genetically distinct from primary colorectal-type adenocarcinoma of the appendix

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Jesinghaus, Moritz; Konukiewitz, Björn; Foersch, Sebastian

2018-01-01

The appendix gives rise to goblet cell carcinoids, which represent special carcinomas with distinct biological and histological features. Their genetic background and molecular relationship to colorectal adenocarcinoma is largely unknown. We therefore performed a next-generation sequencing analysis...... a morphomolecular entity, histologically and genetically distinct from appendiceal colorectal-type adenocarcinomas and its colorectal counterparts. Altered Wnt-signaling associated genes, apart from APC, may act as potential drivers of these neoplasms. The absence of KRAS/NRAS mutations might render some....../adenocarcinoma ex-goblet cell carcinoid (n=2, respectively). Mutations in colorectal cancer-related genes (eg, TP53, KRAS, APC) were rare to absent in both, goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid, but frequent in primary colorectal-type adenocarcinomas of the appendix. Additional large...

Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

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Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-01-01

Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

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2014-05-28

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

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M. Ryan Smith

2016-08-01

Full Text Available Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP, decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231 breast adenocarcinoma cells up to 6 days after an initial 24 h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10 µM of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC protein levels, although other protein levels were

Deleterious effects on MDAMB-231 breast adenocarcinoma cell lineage submitted to Ho-166 radioactive seeds at very low activity

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Falcao, Patricia L.; Campos, Tarcisio P.R., E-mail: campos@nuclear.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear; Sarmento, Eduardo V. [Centro de Desenvolvimento de Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Cuperschmid, Ethel M. [Universidade Federal de Minas Gerais (CEMEMOR/UFMG), Belo Horizonte, BR (Brazil). Fac. de Medicina. Centro de Memoria da Medicina

2011-07-01

Herein, the deleterious effect of ionizing radiation provided by Ho-166 radioactive seeds at low activity were addressed, based on experimental in vitro assays at the MDA MB231 cell lineage, a breast adenocarcinoma, compared to PBMC - peripheral blood cells. The methodology involves of the MDBMB-231 and PBMC expansion in culture in suitable environment in 30mm well plates and T-25 flasks. Seeds were synthesized with Ho-165 incorporated and characterized previously. Activation was processed at IPR1 reactor at the peripheral table, at 8h exposition. Three groups of seeds were tested: 0,34 mCi, 0,12 mCi activity, and control group. Such seeds were placed on culture and held to a period of 05 half-lives of the radionuclide. The biological responses at these exposure were documented by inverse microscopic photographic in time. Also, MTT essay were performed. A fast response in producing deleterious effects at cancer cell was observed even if for the low activity seeds. Also, a biological response dependent to a radial distance of the seed was observed. At conclusion, viability clonogenic control of MDAMB231 is identified at the exposition to Ho-166 ceramic seeds, even if at low activity of 0,1 to 0,3mCi. (author)

Deleterious effects on MDAMB-231 breast adenocarcinoma cell lineage submitted to Ho-166 radioactive seeds at very low activity

International Nuclear Information System (INIS)

Falcao, Patricia L.; Campos, Tarcisio P.R.; Cuperschmid, Ethel M.

2011-01-01

Herein, the deleterious effect of ionizing radiation provided by Ho-166 radioactive seeds at low activity were addressed, based on experimental in vitro assays at the MDA MB231 cell lineage, a breast adenocarcinoma, compared to PBMC - peripheral blood cells. The methodology involves of the MDBMB-231 and PBMC expansion in culture in suitable environment in 30mm well plates and T-25 flasks. Seeds were synthesized with Ho-165 incorporated and characterized previously. Activation was processed at IPR1 reactor at the peripheral table, at 8h exposition. Three groups of seeds were tested: 0,34 mCi, 0,12 mCi activity, and control group. Such seeds were placed on culture and held to a period of 05 half-lives of the radionuclide. The biological responses at these exposure were documented by inverse microscopic photographic in time. Also, MTT essay were performed. A fast response in producing deleterious effects at cancer cell was observed even if for the low activity seeds. Also, a biological response dependent to a radial distance of the seed was observed. At conclusion, viability clonogenic control of MDAMB231 is identified at the exposition to Ho-166 ceramic seeds, even if at low activity of 0,1 to 0,3mCi. (author)

Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

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Michelle Visagie

Full Text Available 2-Methoxyestradiol (2ME2 is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

Effect of acadesine on breast cancer cells under hypoxia

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A. M. Shcherbakov

2017-01-01

Full Text Available The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК, an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen, acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia, acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.

Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines

International Nuclear Information System (INIS)

Plummer, Howard K III; Yu, Qiang; Cakir, Yavuz; Schuller, Hildegard M

2004-01-01

Previous research has indicated that at various organ sites there is a subset of adenocarcinomas that is regulated by beta-adrenergic and arachidonic acid-mediated signal transduction pathways. We wished to determine if this regulation exists in breast adenocarcinomas. Expression of mRNA that encodes a G-protein coupled inwardly rectifying potassium channel (GIRK1) has been shown in tissue samples from approximately 40% of primary human breast cancers. Previously, GIRK channels have been associated with beta-adrenergic signaling. Breast cancer cell lines were screened for GIRK channels by RT-PCR. Cell cultures of breast cancer cells were treated with beta-adrenergic agonists and antagonists, and changes in gene expression were determined by both relative competitive and real time PCR. Potassium flux was determined by flow cytometry and cell signaling was determined by western blotting. Breast cancer cell lines MCF-7, MDA-MB-361 MDA-MB 453, and ZR-75-1 expressed mRNA for the GIRK1 channel, while MDA-MB-468 and MDA-MB-435S did not. GIRK4 was expressed in all six breast cancer cell lines, and GIRK2 was expressed in all but ZR-75-1 and MDA-MB-435. Exposure of MDA-MB-453 cells for 6 days to the beta-blocker propranolol (1 μM) increased the GIRK1 mRNA levels and decreased beta 2 -adrenergic mRNA levels, while treatment for 30 minutes daily for 7 days had no effect. Exposure to a beta-adrenergic agonist and antagonist for 24 hours had no effect on gene expression. The beta adrenergic agonist, formoterol hemifumarate, led to increases in K + flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a high affinity agonist for beta-adrenergic receptors stimulated activation of Erk 1/2 in MDA-MB-453 cells. Our data suggests β-adrenergic receptors and GIRK channels may play a role in breast cancer

Trans- and cis-2-phenylindole platinum(II) complexes as cytotoxic agents against human breast adenocarcinoma cell lines

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Tomé, Maria; López, Concepción; González, Asensio; Ozay, Bahadir; Quirante, Josefina; Font-Bardía, Mercè; Calvet, Teresa; Calvis, Carme; Messeguer, Ramon; Baldomá, Laura; Badía, Josefa

2013-09-01

The synthesis and characterization of the new 2-phenylindole derivative: C8H3N-2-C6H5-3NOMe-5OMe (3c) and the trans- and cis-isomers of [Pt(3c)Cl2(DMSO)] complexes (4c and 5c, respectively) are described. The crystal structures of 4c·CH2Cl2 and 5c confirm: (a) the existence of a Pt-Nindole bond, (b) the relative arrangement of the Cl- ligands [trans- (in 4c) or cis- (in 5c)] and (c) the anti-(E) configuration of the oxime. The cytotoxic assessment of C8H3N-2-(C6H4-4‧R1)-3NOMe-5R2 [with R1 = R2 = H (3a); R1 = Cl, R2 = H (3b) and R1 = H, R2 = OMe (3c)] and the geometrical isomers of [Pt(L)Cl2(DMSO)] with L = 3a-3c [trans- (4a-4c) and cis- (5a-5c), respectively] against human breast adenocarcinoma cell lines (MDA-MB231 and MCF-7) is also reported and reveals that all the platinum(II) complexes (except 4a) are more cytotoxic than cisplatin in front of the MCF7 cell line. Electrophoretic DNA migration studies of the synthesized compounds in the absence and in the presence of topoisomerase-I have been performed, in order to get further insights into their mechanism of action.

Cytotoxic effects of ultra-diluted remedies on breast cancer cells.

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Frenkel, Moshe; Mishra, Bal Mukund; Sen, Subrata; Yang, Peiying; Pawlus, Alison; Vence, Luis; Leblanc, Aimee; Cohen, Lorenzo; Banerji, Pratip; Banerji, Prasanta

2010-02-01

The use of ultra-diluted natural products in the management of disease and treatment of cancer has generated a lot of interest and controversy. We conducted an in vitro study to determine if products prescribed by a clinic in India have any effect on breast cancer cell lines. We studied four ultra-diluted remedies (Carcinosin, Phytolacca, Conium and Thuja) against two human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) and a cell line derived from immortalized normal human mammary epithelial cells (HMLE). The remedies exerted preferential cytotoxic effects against the two breast cancer cell lines, causing cell cycle delay/arrest and apoptosis. These effects were accompanied by altered expression of the cell cycle regulatory proteins, including downregulation of phosphorylated Rb and upregulation of the CDK inhibitor p27, which were likely responsible for the cell cycle delay/arrest as well as induction of the apoptotic cascade that manifested in the activation of caspase 7 and cleavage of PARP in the treated cells. The findings demonstrate biological activity of these natural products when presented at ultra-diluted doses. Further in-depth studies with additional cell lines and animal models are warranted to explore the clinical applicability of these agents.

Effects of Urtica dioica dichloromethane extract on cell apoptosis and related gene expression in human breast cancer cell line (MDA-MB-468).

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Mohammadi, A; Mansoori, B; Goldar, S; Shanehbandi, D; Khaze, V; Mohammadnejad, L; Baghbani, E; Baradaran, B

2016-02-29

Breast cancer is the most common cancer among women in worldwide, especially in developing countries. Therefore, a large number of anticancer agents with herbal origins have been reported against this deadly disease. This study is the first to examine the cytotoxic and apoptotic effects of Urtica dioica in MDA-MB-468, human breast adenocarcinoma cells. The 3-(4,5-dimethylethiazol-2 yl)-2,5- diphenyltetrazolium (MTT) reduction and trypan-blue exclusion assay were performed in MDA-MB-468 cells as well as control cell line L929 to analyze the cytotoxic activity of the dichloromethane extract. In addition, Apoptosis induction of Urtica dioica on the MDA-MB-468 cells was assessed using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis and real-time polymerase chain reaction (PCR). The results showed that the extract significantly inhibited cell growth and viability without inducing damage to normal control cells. Nuclei Staining in TUNEL and DNA fragments in DNA fragmentation assay and increase in the mRNA expression levels of caspase-3, caspase-9, decrease in the bcl2 and no significant change in the caspase-8 mRNA expression level, showed that the induction of apoptosis was the main mechanism of cell death that induce by Urtica dioica extract. Our results suggest that urtica dioica dichloromethane extract may contain potential bioactive compound(s) for the treatment of breast adenocarcinoma.

File list: His.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines hg19 Histone Lung Lung adenocarcino...ma cell lines SRX1143596,SRX1143597,SRX1143598,SRX1143599 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

International Nuclear Information System (INIS)

Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

2013-01-01

There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma

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Myung-Giun Noh

2017-07-01

Full Text Available Background Yes-associated protein (YAP in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10 than in carcinomas with a low Gleason grades (6–7 (p < .01. There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR–free survival was significantly lower in patients with high YAP expressing cancers (p = .02. However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

Trefoil Factor 3 as a Novel Biomarker to Distinguish Between Adenocarcinoma and Squamous Cell Carcinoma

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Wang, Xiao-Nan; Wang, Shu-Jing; Pandey, Vijay; Chen, Ping; Li, Qing; Wu, Zheng-Sheng; Wu, Qiang; Lobie, Peter E.

2015-01-01

Abstract In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an

Neurological manifestation of colonic adenocarcinoma

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Uzair Chaudhary

2012-04-01

Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

The comparison of CT findings between peripheral pulmonary squamous cell carcinoma and pulmonary adenocarcinoma

International Nuclear Information System (INIS)

Tan Guosheng; Yang Xufeng; Zhou Xuhui; Li Ziping; Fan Miao; Chen Jindi

2007-01-01

Objective: To compare the principal HRCT features of peripheral pulmonary squamous cell carcinoma and pulmonary adenocarcinoma and to explore their pathological mechanism, in order to improve the recognition of the CT signs of peripheral pulmonary carcinoma. Methods: The principal HRCT signs of thirty-five cases with pathologically proved peripheral pulmonary squamous cell carcinoma and forty cases with pathologically proved peripheral pulmonary adenocarcinoma were analyzed retrospectively to explore the relationship between CT features and pathological findings. Results: The main features of peripheral pulmonary squamous cell carcinoma included larger masses, clear boundary, superficial sublobes and intra-tumor necrosis. While peripheral pulmonary adenocarcinoma mostly demonstrated as smaller nodules, deep sublobes, spiculations, spiculate protuberance, pleural indentation, vessel converging signs, and vacuole signs. The different of these above findings of peripheral pulmonary squamous cell carcinoma and adenocarcinoma were significant (P<0.05). Peripheral pulmonary squamous cell carcinoma may depict bronchial casts and polygonal nodules; and peripheral pulmonary adenocarcinoma may demonstrate ground glass-like nodules. Conclusion: The difference of the CT findings between peripheral pulmonary squamous cell carcinoma and peripheral adenocarcinoma is based on their different histological features and biological behaviors. It is possible to differentiate them before operation in combination with clinical information. (authors)

Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer Cells

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Tuğba Alarcon Martinez

2018-05-01

Full Text Available Background: Recently, cytotoxic effects of statins on breast cancer cells have been reported. However, the mechanism of anti-proliferative effects is currently unknown. Autophagy is non-apoptotic programmed cell death, which is characterized by degradation of cytoplasmic components and as having a role in cancer pathogenesis. Aims: To investigate the anti-proliferative effects of atorvastatin on MCF-7 human breast adenocarcinoma cells with respect to both autophagy and apoptosis. Study Design: Cell culture study. Methods: Cell viability was analyzed using WST-1 cell proliferation assay. Apoptosis was determined by the TUNEL method, whereas autophagy was assessed by Beclin-1 and LC3B immunofluorescence staining. Ultrastructural analysis of cells was performed by electron microscopy. Results: Atorvastatin reduced MCF-7 cell proliferation in a dose- and time-dependent manner inducing TUNEL-, Beclin-1-, and LC3B-positive cells. Moreover, ultrastructural analysis showed apoptotic, autophagic, and necrotic morphological changes in treatment groups. A statistically significant increase in the apoptotic index was detected with higher concentrations of atorvastatin at 24 h and 48 h (p<0.05. Conclusion: The anti-proliferative effects of atorvastatin on breast cancer cells is mediated by the induction of both apoptosis and autophagy which shows statins as a potential treatment option for breast cancer.

Cytomorphological features of ALK-positive lung adenocarcinomas: psammoma bodies and signet ring cells.

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Pareja, Fresia; Crapanzano, John P; Mansukhani, Mahesh M; Bulman, William A; Saqi, Anjali

2015-03-01

Correlation between histology and genotype has been described in lung adenocarcinomas. For example, studies have demonstrated that adenocarcinomas with an anaplastic lymphoma kinase (ALK) gene rearrangement may have mucinous features. The objective of the current study was to determine whether a similar association can be identified in cytological specimens. A retrospective search for ALK-rearranged cytopathology (CP) and surgical pathology (SP) lung carcinomas was conducted. Additional ALK-negative (-) lung adenocarcinomas served as controls. For CP and SP cases, the clinical data (i.e., age, sex, and smoking history), architecture, nuclear features, presence of mucin-containing cells (including signet ring cells), and any additional salient characteristics were evaluated. The search yielded 20 ALK-positive (+) adenocarcinomas. Compared with patients with ALK(-) lung adenocarcinomas (33 patients; 12 with epidermal growth factor receptor [EGFR]-mutation, 11 with Kristen rat sarcoma [KRAS]-mutation, and 10 wild-type adenocarcinomas), patients with ALK(+) adenocarcinoma presented at a younger age; and there was no correlation noted with sex or smoking status. The most common histological pattern in SP was papillary/micropapillary. Mucinous features were associated with ALK rearrangement in SP specimens. Signet ring cells and psammoma bodies were evident in and significantly associated with ALK(+) SP and CP specimens. However, psammoma bodies were observed in rare adenocarcinomas with an EGFR mutation. Both the ALK(+) and ALK(-) groups had mostly high nuclear grade. Salient features, including signet ring cells and psammoma bodies, were found to be significantly associated with ALK(+) lung adenocarcinomas and are identifiable on CP specimens. Recognizing these may be especially helpful in the molecular triage of scant CP samples. © 2014 American Cancer Society.

Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case report

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Marcelo Lorenzi Marques

Full Text Available CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.

Emerging immunotherapeutics in adenocarcinomas: A focus on CAR-T cells.

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Yazdanifar, Mahboubeh; Zhou, Ru; Mukherjee, Pinku

2016-01-01

More than 80% of all cancers arise from epithelial cells referred to as carcinomas. Adenocarcinomas are the most common type of carcinomas arising from the specialized epithelial cells that line the ducts of our major organs. Despite many advances in cancer therapies, metastatic and treatment-refractory cancers remain the 2 nd leading cause of death. Immunotherapy has offered potential opportunities with specific targeting of tumor cells and inducing remission in many cancer patients. Numerous therapies using antibodies as antagonists or checkpoint inhibitors/immune modulators, peptide or cell vaccines, cytokines, and adoptive T cell therapies have been developed. The most innovative immunotherapy approach so far has been the use of engineered T cell, also referred to as chimeric antigen receptor T cells (CAR-T cells). CAR-T cells are genetically modified naïve T cells that express a chimeric molecule which comprises of the antigen-recognition domains (scFv) of an anti-tumor antibody and one, two, or three intracellular signaling domains of the T cell receptor (TCR). When these engineered T cells recognize and bind to the tumor antigen target via the scFv fragment, a signal is sent to the intracellular TCR domains of the CAR, leading to activation of the T cells to become cytolytic against the tumor cells. CAR-T cell therapy has shown tremendous success for certain hematopoietic malignancies, but this success has not been extrapolated to adenocarcinomas. This is due to multiple factors associated with adenocarcinoma that are different from hematopoietic tumors. Although many advances have been made in targeting multiple cancers by CAR-T cells, clinical trials have shown adverse effects and toxicity related to this treatment. New strategies are yet to be devised to manage side effects associated with CAR-T cell therapies. In this review, we report some of the promising immunotherapeutic strategies being developed for treatment of most common adenocarcinomas with

Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.

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Tsai, Chung-Lin; Chiu, Ying-Ming; Ho, Tin-Yun; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Wu, Yi-Ying

2018-04-01

Gastric cancer is one of the most common malignant cancers with a poor prognosis and high mortality rate worldwide. Current treatment of gastric cancer includes surgery and chemotherapy as the main modalities, but the potentially severe side-effects of chemotherapy present a considerable challenge. Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect against a variety of cancer cells. The purpose of this study was to determine the anti-cancer activity of Galla chinensis and its main component gallic acid on human gastric adenocarcinoma cells. MTT assay and cell death ELISA were used to determine the apoptotic effect of Gallic Chinensis and gallic acid on human gastric adenocarcinoma cells. To determine the pathway and relevant components by which gallic acid-induced apoptosis is mediated through, cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000. Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5 expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced gallic acid-induced cell death. In addition, p53 was shown to be involved in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis in AGS cells. These results suggest that gallic acid has a potential role in the treatment of gastric cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Tissue detection of natural killer cells in colorectal adenocarcinoma

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Patsouris Efstratios S

2004-09-01

Full Text Available Abstract Background Natural killer (NK cells represent a first line of defence against a developing cancer; however, their exact role in colorectal cancer remains undetermined. The aim of the present study was to evaluate the expression of CD16 and CD57 [immunohistochemical markers of natural NK cells] in colorectal adenocarcinoma. Methods Presence of NK cells was investigated in 82 colorectal adenocarcinomas. Immunohistochemical analysis was performed, using 2 monoclonal antibodies (anti-Fc Gamma Receptor II, CD16 and an equivalent to Leu-7, specific for CD-57. The number of immunopositive cells (% was evaluated by image analysis. The cases were characterized according to: patient gender and age, tumor location, size, grade, bowel wall invasion, lymph node metastases and Dukes' stage. Results NK cells were detected in 79/82 cases at the primary tumor site, 27/33 metastatic lymph nodes and 3/4 hepatic metastases; they were detected in levels similar to those reported in the literature, but their presence was not correlated to the clinical or pathological characteristics of the series, except for a negative association with the patients' age (p = 0.031. Conclusions Our data do not support an association of NK cell tissue presence with clinical or pathological variables of colorectal adenocarcinoma, except for a negative association with the patients' age; this might possibly be attributed to decreased adhesion molecule expression in older ages.

Vanadium(III)-l-cysteine enhances the sensitivity of murine breast adenocarcinoma cells to cyclophosphamide by promoting apoptosis and blocking angiogenesis.

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Basu, Abhishek; Bhattacharjee, Arin; Baral, Rathindranath; Biswas, Jaydip; Samanta, Amalesh; Bhattacharya, Sudin

2017-05-01

Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium-based compounds. In addition to its preventive efficacy, studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively toward malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium complex, vanadium(III)-l-cysteine. In this study, vanadium(III)-l-cysteine (1 mg/kg body weight, per os) was administered alone as well as in combination with cyclophosphamide (25 mg/kg body weight, intraperitoneal) in concomitant and pretreatment schedule in mice bearing breast adenocarcinoma cells. The results showed that the combination treatment significantly decreased the tumor burden and enhanced survivability of tumor-bearing mice through generation of reactive oxygen species in tumor cells. These ultimately led to DNA damage, depolarization of mitochondrial membrane potential, and apoptosis in tumor cells. Further insight into the molecular pathway disclosed that the combination treatment caused upregulation of p53 and Bax and suppression of Bcl-2 followed by the activation of caspase cascade and poly (ADP-ribose) polymerase cleavage. Administration of vanadium(III)-l-cysteine also resulted in significant attenuation of peritoneal vasculature and sprouting of the blood vessels by decreasing the levels of vascular endothelial growth factor A and matrix metalloproteinase 9 in the ascites fluid of tumor-bearing mice. Furthermore, vanadium(III)-l-cysteine significantly attenuated cyclophosphamide-induced hematopoietic, hepatic, and genetic damages and provided additional survival advantages. Hence, this study suggested that vanadium(III)-l-cysteine may offer potential therapeutic benefit in combination with cyclophosphamide by augmenting anticancer efficacy and

Estrogen regulation of TRPM8 expression in breast cancer cells

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Chodon, Dechen; Guilbert, Arnaud; Dhennin-Duthille, Isabelle; Gautier, Mathieu; Telliez, Marie-Sophie; Sevestre, Henri; Ouadid-Ahidouch, Halima

2010-01-01

The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer. RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques. TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E 2 , 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca 2+ entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER + ) status of the tumours. Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha

Estrogen-Responsive Genes Overlap with Triiodothyronine-Responsive Genes in a Breast Carcinoma Cell Line

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Nancy Bueno Figueiredo

2014-01-01

Full Text Available It has been well established that estrogen plays an important role in the progression and treatment of breast cancer. However, the role of triiodothyronine (T3 remains controversial. We have previously shown its capacity to stimulate the development of positive estrogen receptor breast carcinoma, induce the expression of genes (PR, TGF-alpha normally stimulated by estradiol (E2, and suppress genes (TGF-beta normally inhibited by E2. Since T3 regulates growth hormones, metabolism, and differentiation, it is important to verify its action on other genes normally induced by E2. Therefore, we used DNA microarrays to compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated with E2 and T3. Several genes were modulated by both E2 and T3 in MCF-7 cells (Student’s t-test, P 2.0, pFDR < 0.05. We confirmed our microarray results by real-time PCR. Our findings reveal that certain genes in MCF-7 cells can be regulated by both E2 and T3.

A case with primary signet ring cell adenocarcinoma of the prostate and review of the literature

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Orcun Celik

2014-06-01

Full Text Available Primary signet cell carcinoma of the prostate is a rare histological variant of prostate malignancies. It is commonly originated from the stomach, colon, pancreas, and less commonly in the bladder. Prognosis of the classical type is worse than the adenocarcinoma of the prostate. Primary signet cell adenocarcinoma is diagnosed by eliminating the adenocarcinomas of other organs such as gastrointestinal tract organs. In this case report, we present a case with primary signet cell adenocarcinoma of the prostate who received docetaxel chemotherapy because of short prostate specific antigen doubling time.

Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells

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Kinjo, T; Kamiyama, K; Chinen, K; Iwamasa, T; Kurihara, K; Hamada, T

2003-01-01

Background/Aim: It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, ...

ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

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Takafumi Kuroda

Full Text Available Cancer stem-like cells (CSCs/cancer-initiating cells (CICs are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas by the ALDEFLUOR assay. ALDH1(high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high cells. ALDH1(high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

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Cheng, Ya-Hsin; Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan; Li, Lih-Ann

2012-01-01

Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

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Cheng, Ya-Hsin [Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Li, Lih-Ann, E-mail: lihann@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China)

2012-03-15

Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

Flavonoid C-glucosides derived from flax straw extracts reduce human breast cancer cell growth in vitro and induce apoptosis.

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Magdalena Czemplik

2016-08-01

Full Text Available Flax straw of flax varieties that are grown for oil production is a byproduct which represents a considerable biomass source. Therefore its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7. The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT and sulforhodamine B (SRB assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic towards MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered. These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells.

trans-11 18:1 Vaccenic Acid (TVA Has a Direct Anti-Carcinogenic Effect on MCF-7 Human Mammary Adenocarcinoma Cells

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Ji-Na Lim

2014-02-01

Full Text Available Trans vaccenic acid (TVA; trans-11 18:1 is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA, a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1 in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products.

WIF-1 and Ihh Expression and Clinical Significance in Patients With Lung Squamous Cell Carcinoma and Adenocarcinoma.

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Zhang, Yue; Hu, Chunhong

2016-10-31

This study investigated the expression of wingless-type inhibitory factor-1 (WIF-1) and Ihh protein in tumor tissues and their clinical significance in patients with lung squamous cell carcinoma and adenocarcinoma. The expression of WIF-1 and Ihh protein in 74 squamous cell carcinomas and 76 adenocarcinomas was measured by immunohistochemistry. The percentage of positive WIF-1 protein expression was significantly higher, while positive Ihh protein expression was significantly lower in patients with well-differentiated lung squamous cell carcinoma and adenocarcinoma, tumor node metastasis (TNM) stage I disease, and lymph node metastasis than that in patients with poorly differentiated tumor, TNM stage III disease, and lymph node metastasis (PIhh protein expression survived significantly shorter than patients with negative Ihh protein expression. In contrast, no significant difference in mean survival was observed in patients with lung squamous cell carcinoma and adenocarcinoma with positive and negative WIF-1 protein expression (P>0.05). Ihh is a marker for poor prognosis in patients with lung squamous cell carcinoma and adenocarcinoma. WIF-1 is not a predictive marker for lung cancer.

Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo model of spontaneous metastatic breast cancer.

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Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Lagioia, Michelle; Gendler, Sandra J; Mukherjee, Pinku

2004-11-01

Cyclooxygenase-2 (COX-2) inhibitors are rapidly emerging as a new generation of therapeutic drug in combination with chemotherapy or radiation therapy for the treatment of cancer. The mechanisms underlying its antitumor effects are not fully understood and more thorough preclinical trials are needed to determine if COX-2 inhibition represents a useful approach for prevention and/or treatment of breast cancer. The purpose of this study was to evaluate the growth inhibitory mechanism of a highly selective COX-2 inhibitor, celecoxib, in an in vivo oncogenic mouse model of spontaneous breast cancer that resembles human disease. The oncogenic mice carry the polyoma middle T antigen driven by the mouse mammary tumor virus promoter and develop primary adenocarcinomas of the breast. Results show that oral administration of celecoxib caused significant reduction in mammary tumor burden associated with increased tumor cell apoptosis and decreased proliferation in vivo. In vivo apoptosis correlated with significant decrease in activation of protein kinase B/Akt, a cell survival signaling kinase, with increased expression of the proapoptotic protein Bax and decreased expression of the antiapoptotic protein Bcl-2. In addition, celecoxib treatment reduced levels of proangiogenic factor (vascular endothelial growth factor), suggesting a role of celecoxib in suppression of angiogenesis in this model. Results from these preclinical studies will form the basis for assessing the feasibility of celecoxib therapy alone or in combination with conventional therapies for treatment and/or prevention of breast cancer.

Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma.

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Cao, Lin-Lin; Du, Changzheng; Liu, Hangqi; Pei, Lin; Qin, Li; Jia, Mei; Wang, Hui

2018-04-01

Lysine-specific demethylase 2A (KDM2A), a specific H3K36me1/2 demethylase, has been reported to be closely associated with several types of cancer. In this study, we aimed to investigate the expression and function of KDM2A in colorectal adenocarcinoma. A total of 215 colorectal adenocarcinoma specimens were collected, and then subjected to immunohistochemistry assay to evaluate the expression levels of KDM2A, cyclin D1 and other proteins in colorectal adenocarcinoma tissues. Real-time polymerase chain reaction, Western blot, and other molecular biology methods were used to explore the role of KDM2A in colorectal adenocarcinoma cells. In this study, we report that the expression level of KDM2A is high in colorectal adenocarcinoma tissues, and this high expression promotes the proliferation and colony formation of colorectal adenocarcinoma cells, as demonstrated by KDM2A knockdown experiments. In addition, the expression of KDM2A is closely associated with cyclin D1 expression in colorectal adenocarcinoma tissues and cell lines. Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.

Cell kinetic parameters of a solid mammary adenocarcinoma

International Nuclear Information System (INIS)

Porschen, R.; Feinendegen, L.E.

1978-01-01

Several cell kinetic parameters of the mammary adenocarcinoma EO 771 were evaluated by means of tumor volume measurements and of 125 I-UdR. The in-situ measured activity loss rate is disturbed by a slow elimination of labelled necrotic cells and by reutilization of 125 I-UdR. The restrictions of the I-UdR method are mentioned and the measured activity loss rates are compared with calculated volume loss rates. (orig./MG) [de

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line.

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Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila M M; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy C R; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

2014-01-01

Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

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Foroulis Christophoros N

2008-12-01

Full Text Available Abstract Background Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. Case presentation A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14. The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. Conclusion This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for

Primary Signet Ring Cell Adenocarcinoma of the Urinary Bladder: A Report of 2 Cases

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Wiem Boukettaya

2014-05-01

Full Text Available Primary signet ring cell carcinoma of the urinary bladder is a rare and aggressive histologic subtype of adenocarcinoma. In general, this tumor occurs in the middle age, and clinical presentation does not differ from transitional cell carcinomas. The prognosis is often poor, given the advanced stage at diagnosis. To our knowledge, <100 cases of signet ring cell adenocarcinoma of the urinary bladder have been reported. We report 2 cases with bladder linitis plastica primitive, and we draw attention to its pathologic, anatomoclinical, and evolution specificity to optimize its therapeutic management.

Malignant myoepithelial cells are associated with the differentiated papillary structure and metastatic ability of a syngeneic murine mammary adenocarcinoma model

International Nuclear Information System (INIS)

Bumaschny, Viviana; Urtreger, Alejandro; Diament, Miriam; Krasnapolski, Martín; Fiszman, Gabriel; Klein, Slobodanka; Joffé, Elisa Bal de Kier

2004-01-01

The normal duct and lobular system of the mammary gland is lined with luminal and myoepithelial cell types. Although evidence suggests that myoepithelial cells might suppress tumor growth, invasion and angiogenesis, their role remains a major enigma in breast cancer biology and few models are currently available for exploring their influence. Several years ago a spontaneous transplantable mammary adenocarcinoma (M38) arose in our BALB/c colony; it contains a malignant myoepithelial cell component and is able to metastasize to draining lymph nodes and lung. To characterize this tumor further, primary M38 cultures were established. The low-passage LM38-LP subline contained two main cell components up to the 30th subculture, whereas the higher passage LM38-HP subline was mainly composed of small spindle-shaped cells. In addition, a large spindle cell clone (LM38-D2) was established by dilutional cloning of the low-passage MM38-LP cells. These cell lines were studied by immunocytochemistry, electron microscopy and ploidy, and syngeneic mice were inoculated subcutaneously and intravenously with the different cell lines, either singly or combined to establish their tumorigenic and metastatic capacity. The two subpopulations of LM38-LP cultures were characterized as luminal and myoepithelium-like cells, whereas LM38-HP was mainly composed of small, spindle-shaped epithelial cells and LM38-D2 contained only large myoepithelial cells. All of them were tumorigenic when inoculated into syngeneic mice, but only LM38-LP cultures containing both conserved luminal and myoepithelial malignant cells developed aggressive papillary adenocarcinomas that spread to lung and regional lymph nodes. The differentiated histopathology and metastatic ability of the spontaneous transplantable M38 murine mammary tumor is associated with the presence and/or interaction of both luminal and myoepithelial tumor cell types

Extracts of strawberry fruits induce intrinsic pathway of apoptosis in breast cancer cells and inhibits tumor progression in mice.

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Ranganatha R Somasagara

Full Text Available The consumption of berry fruits, including strawberries, has been suggested to have beneficial effects against oxidative stress mediated diseases. Berries contain multiple phenolic compounds and secondary metabolites that contribute to their biological properties.Current study investigates the anticancer activity of the methanolic extract of strawberry (MESB fruits in leukaemia (CEM and breast cancer (T47D cell lines ex vivo, and its cancer therapeutic and chemopreventive potential in mice models. Results of MTT, trypan blue and LDH assays suggested that MESB can induce cytotoxicity in cancer cells, irrespective of origin, in a concentration- and time-dependent manner. Treatment of mice bearing breast adenocarcinoma with MESB blocked the proliferation of tumor cells in a time-dependent manner and resulted in extended life span. Histological and immunohistochemical studies suggest that MESB treatment affected tumor cell proliferation by activating apoptosis and did not result in any side effects. Finally, we show that MESB can induce intrinsic pathway of apoptosis by activating p73 in breast cancer cells, when tumor suppressor gene p53 is mutated.The present study reveals that strawberry fruits possess both cancer preventive and therapeutic values and we discuss the mechanism by which it is achieved.

A hybrid of coumarin and phenylsulfonylfuroxan induces caspase-dependent apoptosis and cytoprotective autophagy in lung adenocarcinoma cells.

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Wang, Qian; Guo, Yalan; Jiang, Shanshan; Dong, Mengxue; Kuerban, Kudelaidi; Li, Jiyang; Feng, Meiqing; Chen, Ying; Ye, Li

2018-01-15

Lung adenocarcinoma is the most primary histologic subtype of non-small cell lung cancer (NSCLC). Compound 8b, a novel coumarin derivative with phenylsulfonylfuroxan group, shows significant antiproliferation activity against lung adenocarcinoma cell with low toxicity. This study aims to uncover the potential of compound 8b in relation to apoptosis as well as autophagy induction in lung adenocarcinoma cells. The cytotoxicity and apoptosis of A549 and H1299 cells induced by compound 8b were detected by MTT, microscope and western blot analysis. Autophagy was determined by TEM, confocal microscopy and western blot analysis. Akt/mTOR and Erk signaling pathway were also examined by western blot analysis. First, significant growth inhibition and caspase-dependent apoptosis were observed in compound 8b-treated A549 and H1299 cells. Then, we confirmed compound 8b-induced autophagy by autophagosomes formation, upregulated expression of autophagy-related protein LC3-II and autophagic flux. Importantly, abolishing autophagy using inhibitors and ATG5 siRNA enhanced the cytotoxicity of compound 8b, indicating the cytoprotective role of autophagy in lung adenocarcinoma. Further mechanistic investigations suggested that Akt/mTOR and Erk signaling pathways contributed to autophagy induction by compound 8b. This results demonstrate that compound 8b induces caspase-dependent apoptosis as well as cytoprotective autophagy in lung adenocarcinoma cells, which may provide scientific evidence for developing this furoxan-based NO-releasing coumarin derivative as a potential anti-lung adenocarcinoma therapeutic agents. Copyright © 2017 Elsevier GmbH. All rights reserved.

Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma

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Lipika Lipi

2014-01-01

Full Text Available A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.

Neurinoma del plexo braquial simulando metastasis de adenocarcinoma de mama Schwannoma of the brachial plexus resembling a breast adenocarcinoma metastasis

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Gregorio Rodríguez Boto

2011-10-01

Full Text Available Los neurinomas del plexo braquial son tumores infrecuentes que pueden confundirse con otras lesiones de índole tumoral. Se presenta el caso de una mujer de 40 años, tratada previamente de un adenocarcinoma de mama derecha en el pasado, que en el estudio de extensión realizado 5 años después se detectó una lesión localizada en el plexo braquial derecho. La paciente se encontraba asintomática. El diagnóstico radiológico de presunción fue metástasis de adenocarcinoma mamario. Se realizó un abordaje axilar derecho descubriendo una lesión bien delimitada en el plexo braquial. Con ayuda de la monitorización neurofisiológica intraoperatoria, se observó que la lesión dependía de la rama cubital y se pudo realizar una resección completa preservando la función de dicho nervio. El estudio anatomopatológico confirmó que se trataba de un neurinoma, descartando así la existencia de metástasis. La evolución postoperatoria fue satisfactoria. Seis años después de la intervención no existe recidiva tumoral. En nuestro conocimiento este es el primer caso publicado en la literatura de un neurinoma del plexo braquial dependiente de la rama cubital. La monitorización neurofisiológica intraoperatoria resulta fundamental para abordar este tipo de lesiones con baja morbilidad.Schwa nomas originating from the brachial plexus, although rare, may be mistaken for another type of tumour. A 40 year-old woman, who had been treated years earlier for a breast adenocarcinoma, showed in the 5-year follow-up magnetic resonance examination a localized lesion in the right brachial plexus. The presumptive radiological diagnosis was a metastasis from the primary adenocarcinoma. Following surgical access via the right axilla, a well-circumscribed mass in the brachial plexus was detected. Under intraoperative electrophysiological guidance, the lesion was observed to depend on the ulnar nerve and its complete resection was possible without compromising nerve

Apoptotic-like tumor cells and apoptotic neutrophils in mitochondrion-rich gastric adenocarcinomas: a comparative study with light and electronmicroscopy between these two forms of cell death

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Antonio Venuti

2013-04-01

Full Text Available Mitochondrion-rich adenocarcinomas represent a rare variant of gastric adenocarcinomas composed predominantly of columnar adenocarcinoma cells with eosinophilic cytoplasm, a strong supranuclear immunoreactivity for antimitochondrial antibody, and a marked neutrophil infiltration associated to tumor cell death. The purpose of this work is to investigate, using correlated light and electron microscopy, mitochondrion-rich gastric adenocarcinomas focusing on the nature of the death in neoplastic cells and in infiltrating neutrophils. Adenocarcinoma cells, single or in small clusters, showed convoluted nuclei, irregularly condensed chromatin, loss of microvilli, and nuclear envelope dilatation. No nuclear fragmentation was observed in these dying cells and the plasma membrane did not show signs of disruption. These ultrastructural findings represent intermediate aspects between apoptosis and necrosis and are compatible with apoptosis-like programmed cell death. By contrast, some infiltrating neutrophils showed ultrastructural signs of classic apoptosis such as chromatin condensation into compact geometric (globular, crescent-shaped figures, tightly packed cytoplasmic granules and intact cell membrane. Our study provides ultrastructural evidence of apoptosis-like tumour cell death in mitochondrion-rich gastric carcinomas and confirms that stereotyped outcome either as apoptosis or necrosis of tumor cells cannot always be expected in human neoplasms.

Correlation of matrix metalloproteinases and their inhibitors with hypoxia and angiogenesis in premenopausal patients with adenocarcinoma of the breast.

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Vinothini, Govindarajah; Aravindraja, Chairmandurai; Chitrathara, K; Nagini, Siddavaram

2011-08-01

The present study was designed to correlate the expression of proteins regulating invasion and angiogenesis in patients with adenocarcinoma of the breast. Seventy-five premenopausal breast cancer patients histologically categorized as grades I, II and III were chosen for the study. We analyzed the expression of MMP-2, and -9 and their inhibitors TIMP-2 and RECK together with HIF-1α and VEGF in tumor, adjacent tissues and serum samples by immunohistochemical and Western blot analysis. The breast tumors analyzed in the present study were characterized by increased expression of MMP-2, -9, HIF-1α and VEGF with differential expression patterns of TIMP-2 and downregulation of RECK. The simultaneous analysis of the expression of these molecular markers is important to understand the intricate network between key molecules involved in invasion and angiogenesis that eventually determines the clinical course of the disease. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma

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Yuan, Yang; Wang, Weixing; Li, Huizhong; Yu, Yongwei; Tao, Jin; Huang, Shengdong; Zeng, Zhiyong

2015-01-01

Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS

Treatment of squamous cell and adenocarcinoma of the esophagus

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Rathbone B

2012-11-01

Full Text Available Barrie Rathbone,1 Janusz Jankowski,2 Michael Rathbone31University Hospitals of Leicester, Leicester, 2Sir James Black Professor Queen Mary University of London, 3St George's University of London, London, United KingdomAbstract: Esophageal cancer is the sixth commonest cause of cancer death worldwide. It predominantly occurs in two histological types, ie, squamous cell carcinoma and adenocarcinoma, each with its own distinct geographical distribution and natural history. The incidence of esophageal adenocarcinoma is rising, as is that of its precursor lesion, Barrett's esophagus, which consists of metaplastic change in the squamous mucosa of the esophagus in response to damage by gastroesophageal reflux disease. The principal risk factors for esophageal cancer are cigarette smoking and alcohol consumption, reflux disease, and obesity. In tumors without local invasion or distant metastases, surgery remains the treatment option of choice, although there are considerable differences of opinion regarding the roles of chemotherapy and radiotherapy. A wide variety of endoscopic treatments are available for dysplastic lesions and palliation. Despite the availability of increasingly complex imaging modalities and expensive and possibly ineffective attempts at screening, the evidence base is conflicted and the prognosis remains poor. However, from a recent large systematic review, three clear recommendations can be made, ie, use of endoscopic resection for high grade dysplasia, use of radiofrequency ablation for residual premalignant lesions, and, finally, prevention of risk factors for cancer, such as smoking, alcohol consumption, and obesity.Keywords: cancer, Barrett's, esophagus, squamous cell carcinoma, adenocarcinoma

Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells

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Hai-Bo Xing

2018-01-01

Full Text Available Pancreatic adenocarcinoma has an exceedingly poor prognosis, accounting for five-year survival of less than 5%. Presently, improving the efficacy of pancreatic adenocarcinoma treatment has been the focus of medical researchers worldwide. Recently, it has been suggested that deregulation of interleukin- (IL- 6 is caused by a key gene involved in the beginning and development of pancreatic adenocarcinoma. Herein, we investigated whether suppression of IL-6 could augment gemcitabine sensitivity in the PANC-1 cells. We found considerably higher expression of IL-6 in pancreatic adenocarcinoma tissues than that in the adjacent nontumorous tissues. Suppression of IL-6 by shRNA resulted in apoptosis as well as inhibition of cell proliferation and tumorigenicity. In addition, suppression of IL-6 remarkably promoted antitumor effect of gemcitabine, indicating that the combination of shRNA targeting IL-6 with gemcitabine may provide a potential clinical approach for pancreatic cancer therapy.

Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells

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Mishra, Nawneet; Timilsina, Uddhav; Ghimire, Dibya; Dubey, Ravi C.; Gaur, Ritu

2017-01-01

Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed in a tissue specific manner and have been implicated in cancer cell metabolism although their molecular and regulatory mechanisms are not clearly understood. In this study, we aimed at identifying novel gene signatures in lung cancer. We performed extensive analysis of seven different Gene Expression Omnibus (GEO) datasets pertaining to different stages of lung adenocarcinoma and identified that multiple subunits of COX genes are differentially expressed in these patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be highly down regulated in these patients. In order to validate the GEO datasets, we looked at the expression of multiple COX genes using quantitative real time PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed that COX 7A1 gene expression was indeed highly reduced in these cells. Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell proliferation and increase in cell death via apoptosis. These results indicated that low level of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression.

Prognosis of oesophageal adenocarcinoma and squamous cell carcinoma following surgery and no surgery in a nationwide Swedish cohort study

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Mattsson, Fredrik

2018-01-01

Objectives To assess the recent prognostic trends in oesophageal adenocarcinoma and oesophageal squamous cell carcinoma undergoing resectional surgery and no such surgery. Additionally, risk factors for death were assessed in each of these patient groups. Design Cohort study. Setting A population-based, nationwide study in Sweden. Participants All patients diagnosed with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma in Sweden from 1 January 1990 to 31 December 2013, with follow-up until 14 May 2017. Outcome measures Observed and relative (to the background population) 1-year, 3-year and 5-year survivals were analysed using life table method. Multivariable Cox regression provided HR with 95% CI for risk factors of death. Results Among 3794 patients with oesophageal adenocarcinoma and 4631 with oesophageal squamous cell carcinoma, 82% and 63% were men, respectively. From 1990–1994 to 2010–2013, the relative 5-year survival increased from 12% to 15% for oesophageal adenocarcinoma and from 9% to 12% for oesophageal squamous cell carcinoma. The corresponding survival following surgery increased from 27% to 45% in oesophageal adenocarcinoma and from 24% to 43% in oesophageal squamous cell carcinoma. In patients not undergoing surgery, the survival increased from 3% to 4% for oesophageal adenocarcinoma and from 3% to 6% for oesophageal squamous cell carcinoma. Women with oesophageal squamous cell carcinoma had better prognosis than men both following surgery (HR 0.71, 95% CI 0.61 to 0.83) and no surgery (HR 0.86, 95% CI 0.81 to 0.93). Conclusions The prognosis has improved over calendar time both in oesophageal adenocarcinoma and oesophageal squamous cell carcinoma in Sweden that did and did not undergo surgery. Women appear to have better prognosis in oesophageal squamous cell carcinoma than men, independent of treatment. PMID:29748347

Administration of the optimized β-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model.

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Seoane, Samuel; Díaz-Rodríguez, Patricia; Sendon-Lago, Juan; Gallego, Rosalia; Pérez-Fernández, Román; Landin, Mariana

2013-08-01

β-Lapachone (β-Lap) is a 1,2-orthonaphthoquinone that selectively induces cell death in human cancer cells through NAD(P)H:quinone oxidoreductase-1 (NQO1). NQO1 is overexpressed in a variety of tumors, as compared to normal adjacent tissue. However, the low solubility and non-specific distribution of β-Lap limit its suitability for clinical assays. We formulated β-Lap in an optimal random methylated-β-cyclodextrin/poloxamer 407 mixture (i.e., β-Lap ternary system) and, using human breast adenocarcinoma MCF-7 cells and immunodeficient mice, performed in vitro and in vivo evaluation of its anti-tumor effects on proliferation, cell cycle, apoptosis, DNA damage, and tumor growth. This ternary system is fluid at room temperature, gels over 29 °C, and provides a significant amount of drug, thus facilitating intratumoral delivery, in situ gelation, and the formation of a depot for time-release. Administration of β-Lap ternary system to MCF-7 cells induces an increase in apoptosis and DNA damage, while producing no changes in cell cycle. Moreover, in a mouse xenograft tumor model, intratumoral injection of the system significantly reduces tumor volume, while increasing apoptosis and DNA damage without visible toxicity to liver or kidney. These anti-tumoral effects and lack of visible toxicity make this system a promising new therapeutic agent for breast cancer treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of Rac1 Pathway in Epithelial-to-Mesenchymal Transition and Cancer Stem-like Cell Phenotypes in Gastric Adenocarcinoma.

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Yoon, Changhwan; Cho, Soo-Jeong; Chang, Kevin K; Park, Do Joong; Ryeom, Sandra W; Yoon, Sam S

2017-08-01

Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma, but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 activity and inhibition were examined in gastric adenocarcinoma cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44 + gastric adenocarcinoma CSCs compared with unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78%-81%, and prevented tumor initiation in immunodeficient mice. Gastric adenocarcinoma CSCs had increased expression of the EMT transcription factor Slug, 4.4- to 8.3-fold greater migration, and 4.2- to 12.6-fold greater invasion than unselected cells, and these increases could be blocked completely with Rac1 inhibition. Gastric adenocarcinoma spheroid cells were resistant to 5-fluorouracil and cisplatin chemotherapy, and this chemotherapy resistance could be reversed with Rac1 shRNA or NSC23766. The PI3K/Akt pathway may be upstream of Rac1, and JNK may be downstream of Rac1. In the MKN-45 xenograft model, cisplatin inhibited tumor growth by 50%, Rac1 inhibition by 35%, and the combination by 77%. Higher Rac1 activity, in clinical specimens from gastric adenocarcinoma patients who underwent potentially curative surgery, correlated with significantly worse survival ( P = 0.017). In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy. Implications: In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance. Mol

Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

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Siwen WANG

2011-09-01

Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus.

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Kilic, Ergin; Tennstedt, Pierre; Högner, Anica; Lebok, Patrick; Sauter, Guido; Bokemeyer, Carsten; Izbicki, Jakob R; Wilczak, Waldemar

2016-04-01

SALL4 is a transcription factor originally identified as a homeotic gene essential for organ development. Early studies suggested that SALL4 is a useful marker to identify testicular and ovarian germ cell tumors. The aim of the study was to evaluate the diagnostic potential of SALL4 immunohistochemistry. Immunohistochemical staining was performed on a tissue microarray (TMA) with 3966 samples from 94 different tumor types and on a further TMA with 492 esophagus carcinomas. SALL4 immunostaining was by far most prevalent and most intensive in testicular tumors with a positivity rate of 93.1% in seminomas, 80% in mixed germ cell tumors (embryonic carcinomas/yolk sac tumors), and 18.5% in teratomas, respectively. However, SALL4 expression is not specific to germ cell tumors. We observed SALL4 positivity in non-germ cell tumors as carcinomas of the kidney (28.9% of chromophobe, 34.4% of clear cell carcinoma), in intestinal type adenocarcinoma of the stomach (10.9%), in adenocarcinoma (10.5%) and squamous cell carcinoma (7.2%) of the esophagus, and in malignant melanoma (8.1%) and invasive urothelial bladder carcinoma (20%). SALL4 expression was not found in lymphomas, in soft tissue tumors or breast tumors. At analysis of esophagus carcinoma TMA, no significant association was seen between SALL4 expression and overall survival in adenocarcinoma. However, SALL4 expression was strongly associated with worse overall survival in squamous cell carcinoma. SALL4 expression can be found at relevant frequencies in various tumors of different primary sites. SALL4 expression in squamous cell carcinoma of the esophagus may constitute a sign of dedifferentiation leading to poor patient prognosis.

Modulating the vascular behavior of metastatic breast cancer cells by curcumin treatment

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Palange, Anna L. [Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX (United States); Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX (United States); Mascolo, Daniele Di [Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX (United States); Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX (United States); Department of Experimental and Clinical Medicine, University of Magna Graecia, Catanzaro (Italy); Singh, Jaykrishna [Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX (United States); Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX (United States); Franceschi, Maria S. De; Carallo, Claudio; Gnasso, Agostino [Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX (United States); Decuzzi, Paolo, E-mail: pdecuzzi@tmhs.org [Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX (United States); Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX (United States); Department of Experimental and Clinical Medicine, University of Magna Graecia, Catanzaro (Italy)

2012-11-15

The spreading of tumor cells to secondary sites (tumor metastasis) is a complex process that involves multiple, sequential steps. Vascular adhesion and extravasation of circulating tumor cells (CTCs) is one, critical step. Curcumin, a natural compound extracted from Curcuma longa, is known to have anti-tumoral, anti-proliferative, anti-inflammatory properties and affect the expression of cell adhesion molecules, mostly by targeting the NF-κB transcription factor. Here, upon treatment with curcumin, the vascular behavior of three different estrogen receptor negative (ER{sup –}) breast adenocarcinoma cell lines (SK-BR-3, MDA-MB-231, MDA-MB-468) is analyzed using a microfluidic system. First, the dose response to curcumin is characterized at 24, 48, and 72 h using a XTT assay. For all three cell lines, an IC{sub 50} larger than 20 µM is observed at 72 h; whereas no significant reduction in cell viability is detected for curcumin concentrations up to 10 µM. Upon 24 h treatment at 10 µM of curcumin, SK-BR3 and MDA-MB-231 cells show a decrease in adhesion propensity of 40% (p = 0.02) and 47% (p = 0.001), respectively. No significant change is documented for the less metastatic MDA-MB-468 cells. All three treated cell lines show a 20% increase in rolling velocity from 48.3 to 58.7 µm/s in SK-BR-3, from 64.1 to 73.77 µm/s in MDA-MB-231, and from 57.5 to 74.4 µm/s in MDA-MB-468. Collectively, these results suggest that mild curcumin treatments could limit the metastatic potential of these adenocarcinoma cell lines, possibly by altering the expression of adhesion molecules, and the organization and stiffness of the cell cytoskeleton. Future studies will elucidate the biophysical mechanisms regulating this curcumin-induced behavior and further explore the clinical relevance of these findings.

Modulating the vascular behavior of metastatic breast cancer cells by curcumin treatment

International Nuclear Information System (INIS)

Palange, Anna L.; Mascolo, Daniele Di; Singh, Jaykrishna; Franceschi, Maria S. De; Carallo, Claudio; Gnasso, Agostino; Decuzzi, Paolo

2012-01-01

The spreading of tumor cells to secondary sites (tumor metastasis) is a complex process that involves multiple, sequential steps. Vascular adhesion and extravasation of circulating tumor cells (CTCs) is one, critical step. Curcumin, a natural compound extracted from Curcuma longa, is known to have anti-tumoral, anti-proliferative, anti-inflammatory properties and affect the expression of cell adhesion molecules, mostly by targeting the NF-κB transcription factor. Here, upon treatment with curcumin, the vascular behavior of three different estrogen receptor negative (ER – ) breast adenocarcinoma cell lines (SK-BR-3, MDA-MB-231, MDA-MB-468) is analyzed using a microfluidic system. First, the dose response to curcumin is characterized at 24, 48, and 72 h using a XTT assay. For all three cell lines, an IC 50 larger than 20 µM is observed at 72 h; whereas no significant reduction in cell viability is detected for curcumin concentrations up to 10 µM. Upon 24 h treatment at 10 µM of curcumin, SK-BR3 and MDA-MB-231 cells show a decrease in adhesion propensity of 40% (p = 0.02) and 47% (p = 0.001), respectively. No significant change is documented for the less metastatic MDA-MB-468 cells. All three treated cell lines show a 20% increase in rolling velocity from 48.3 to 58.7 µm/s in SK-BR-3, from 64.1 to 73.77 µm/s in MDA-MB-231, and from 57.5 to 74.4 µm/s in MDA-MB-468. Collectively, these results suggest that mild curcumin treatments could limit the metastatic potential of these adenocarcinoma cell lines, possibly by altering the expression of adhesion molecules, and the organization and stiffness of the cell cytoskeleton. Future studies will elucidate the biophysical mechanisms regulating this curcumin-induced behavior and further explore the clinical relevance of these findings.

Modulating the vascular behavior of metastatic breast cancer cells by curcumin treatment

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Anna Lisa ePalange

2012-11-01

Full Text Available The spreading of tumor cells to secondary sites (tumor metastasis is a complex process that involves multiple, sequential steps. Vascular adhesion and extravasation of circulating tumor cells (CTCs is one, critical step. Curcumin, a natural compound extracted from Curcuma longa, is known to have anti-tumoral, anti-proliferative, anti-inflammatory properties and affect the expression of cell adhesion molecules, mostly by targeting the NF-κB transcription factor. Here, upon treatment with Curcumin, the vascular behavior of three different estrogen receptor negative (ER– breast adenocarcinoma cell lines (SK-BR-3, MDA-MB-231, MDA-MB-468 is analyzed using a microfluidic system. First, the dose response to curcumin is characterized at 24, 48 and 72h using a XTT assay. For all three cell lines, an IC50 larger than 20 µM is observed at 72 h; whereas no significant reduction in cell viability is detected for curcumin concentrations up to 10 µM. Upon 24 h treatment at 10 µM of curcumin, SK-BR3 and MDA-MB-231 cells show a decrease in adhesion propensity of 40% (p = 0.02 and 47% (p = 0.001, respectively. No significant change is documented for the less metastatic MDA-MB-468 cells. All three treated cell lines show a 20% increase in rolling velocity from 48.3 to 58.7 µm/s in SK-BR-3, from 64.1 to 73.77 µm/s in MDA-MB-231 and from 57.5 to 74.4 µm/s in MDA-MB-468. Collectively, these results suggest that mild curcumin treatments could limit the metastatic potential of these adenocarcinoma cell lines, possibly by altering the expression of adhesion molecules, and the organization and stiffness of the cell cytoskeleton. Future studies will elucidate the biophysical mechanisms regulating this curcumin-induced behavior and further explore the clinical relevance of these findings.

Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

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Zhang, Hui; Guo, Qiufen; Wang, Chong; Yan, Lei; Fu, Yibing; Fan, Mingjun; Zhao, Xingbo; Li, Mingjiang

2013-08-25

Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Copyright © 2013. Published by Elsevier Ireland Ltd.

Identification of Luminal Breast Cancers that Establish a Tumor Supportive Macroenvironment Defined by Pro-Angiogenic Platelets and Bone Marrow Derived Cells

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Kuznetsov, Hanna S.; Marsh, Timothy; Markens, Beth A.; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A.; Brown, Victoria E.; Richardson, Andrea L.; Signoretti, Sabina; Battinelli, Elisabeth M.; McAllister, Sandra S.

2012-01-01

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer cells and patient tumor specimens (LBC “instigators”) establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors (“responders”). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells (BMCs) enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGFR2+ tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. PMID:22896036

EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice.

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Alexei Shir

2006-01-01

Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most lethal form of brain cancer. With the available treatments, survival does not exceed 12-14 mo from the time of diagnosis. We describe a novel strategy to selectively induce the death of glioblastoma cells and other cancer cells that over-express the EGF receptor. Using a non-viral delivery vector that homes to the EGF receptor, we target synthetic anti-proliferative dsRNA (polyinosine-cytosine [poly IC], a strong activator of apoptosis, selectively to cancer cells. METHODS AND FINDINGS: Poly IC was delivered by means of a non-viral vector: 25kDa polyethylenimine-polyethyleneglycol-EGF (PEI25-PEG-EGF. EGFR-targeted poly IC induced rapid apoptosis in the target cells in vitro and in vivo. Expression of several cytokines and "bystander killing" of untransfected tumor cells was detected in vitro and in vivo. Intra-tumoral delivery of the EGFR-targeted poly IC induced the complete regression of pre-established intracranial tumors in nude mice, with no obvious adverse toxic effects on normal brain tissue. A year after treatment completion the treated mice remain cancer-free and healthy. Similarly, non-viral delivery of poly IC completely eliminated pre-established breast cancer and adenocarcinoma xenografts derived from EGFR over-expressing cancer cell lines, suggesting that the strategy is applicable to other EGFR-over-expressing tumors. CONCLUSION: The strategy described has yielded an effective treatment of EGFR over-expressing GBM in an animal model. If this strategy is translated successfully to the clinical setting, it may actually offer help to GBM patients. Moreover the elimination of two additional EGFR over-expressing cancers in vivo suggests that in principle this strategy can be applied to treat other tumors that over-express EGFR.

Fine-needle aspiration of gray zone lesions of the breast: fibroadenoma versus ductal carcinoma.

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Jing, Xin; Normolle, Daniel; Michael, Claire W

2013-09-01

While breast lesions have characteristic cytological features, some lesions, particularly adenocarcinoma and fibroadenoma, may present with overlapping features causing erroneous diagnoses. The current study aimed to define significant cytomorphologic features predictive of fibroadenoma and adenocarcinoma, respectively. Further, we intended to evaluate the predictive characteristics for differentiation between gray zone lesions and to identify root causes contributing to misdiagnoses. First, direct smears prepared from 14 histology-confirmed fibroadenomas and 14 adenocarcinomas were reviewed and characteristics of commonly encountered morphologic features were assessed. We then retrospectively and blindly reviewed nine cytohistologic discrepant cases using the significant characteristic as a guideline, in order to assess whether these discrepant cases could be correctly categorized. Morphologic characteristics predictive of fibroadenoma included moderate cellularity, large, folded cellular sheets/aggregates, staghorn projections, smooth and round borders, monolayers, honeycomb arrangement, smaller nuclear size, and background bipolar cells. Predictive characteristics of adenocarcinoma included high cellularity, loose cohesive sheets/aggregates, pointed projections, irregular borders, larger nuclear size, irregular nuclear membrane, prominent nucleoli, and single atypical epithelial cells. Retrospective, blind review correctly re-classified seven out of nine cytohistologic discrepant cases, including five false negative cases and two false positive cases. Root causes contributing to the misdiagnoses were large branching sheets of carcinoma mimicking folded sheets of fibroadenoma; fibroblasts mimicking myoepithelial cells; apocrine cells mimicking carcinoma cells; and not recognizing the loose myxoid matrix presenting as soap bubbles in fibroadenoma. In conclusion, this study identified significant characteristics that can assist in achieving accurate diagnosis in a

CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells

International Nuclear Information System (INIS)

Androutsopoulos, Vasilis P.; Ruparelia, Ketan; Arroo, Randolph R.J.; Tsatsakis, Aristidis M.; Spandidos, Demetrios A.

2009-01-01

Among the different mechanisms proposed to explain the cancer-protecting effect of dietary flavonoids, substrate-like interactions with cytochrome P450 CYP1 enzymes have recently been explored. In the present study, the metabolism of the flavonoids chrysin, baicalein, scutellarein, sinensetin and genkwanin by recombinant CYP1A1, CYP1B1 and CYP1A2 enzymes, as well as their antiproliferative activity in MDA-MB-468 human breast adenocarcinoma and MCF-10A normal breast cell lines, were investigated. Baicalein and 6-hydroxyluteolin were the only conversion products of chrysin and scutellarein metabolism by CYP1 family enzymes, respectively, while baicalein itself was not metabolized further. Sinensetin and genkwanin produced a greater number of metabolites and were shown to inhibit strongly in vitro proliferation of MDA-MB-468 cells at submicromolar and micromolar concentrations, respectively, without essentially affecting the viability of MCF-10A cells. Cotreatment of the CYP1 family inhibitor acacetin reversed the antiproliferative activity noticed for the two flavones in MDA-MB-468 cells to 13 and 14 μM respectively. In contrast chrysin, baicalein and scutellarein inhibited proliferation of MDA-MB-468 cells to a lesser extent than sinensetin and genkwanin. The metabolism of genkwanin to apigenin and of chrysin to baicalein was favored by CYP1B1 and CYP1A1, respectively. Taken together the data suggests that CYP1 family enzymes enhance the antiproliferative activity of dietary flavonoids in breast cancer cells, through bioconversion to more active products.

Basal cell adenocarcinoma of minor salivary and seromucous glands of the head and neck region.

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Fonseca, I; Soares, J

1996-05-01

Basal cell adenocarcinoma of salivary glands is an uncommon and recently described entity occurring almost exclusively at the major salivary glands. This report provides an overview of the clinicopathologic profile of this neoplasm by including the personal experience on the clinical features, microscopic and ultrastructural characteristics, proliferation activity, and DNA tumor patterns of 12 lesions occurring at the minor salivary glands of the head and neck region, where basal cell adenocarcinoma is probably an underecognized entity, previously reported under different designations. Basal cell adenocarcinoma predominates at the seventh decade without sex preference. The tumors affecting the minor salivary glands occur most frequently at the oral cavity (jugal mucosa, palate) and the upper respiratory tract. The prevalent histologic tumor pattern is represented by solid neoplastic aggregates with a peripheral cell palisading arrangement frequently delineated by basement membrane-like material. The neoplastic clusters are formed by two cell populations: the small dark cell type (that predominates) and a large cell type. Necrosis, either of the comedo or the apoptotic type, is a frequent finding. Perineural growth occurs in 50% of the cases and vascular permeation in 25%. Immunohistochemistry identifies a dual differentiation with a reactivity pattern indicative of ductal epithelial and myoepithelial differentiation, which can be confirmed by electron microscopy. The differential diagnosis of the neoplasm includes its benign counterpart, the basal cell adenoma, solid variant of adenoid cystic carcinoma, undifferentiated carcinoma, and basaloid squamous carcinoma. The tumors recur more frequently than lesions originating in major salivary glands. Mortality is associated with the anatomic site of the lesion, advanced stage, residual neoplasia at surgery, and tumor recurrence. The importance of recognizing basal cell adenocarcinoma outside major salivary glands is

Experiment list: SRX099869 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available of Extraction=Pleura|Tissue Diagnosis=Adenocarcinoma 30024170,98.2,3.9,1267 GSM808758: MCF7 INPUT source_name=breast adenocarcinoma... cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibody=INPUT h

Apoptotic Effect of the Urtica Dioica Plant Extracts on Breast Cancer Cell Line (MDA- MB- 468

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A Mohammadi

2015-09-01

Full Text Available Background & objectives: Cancer is one of the most causes of mortality in worldwide. Components derived from natural plants that induce apoptosis are used for cancer treatment. Therefore investigation of different herbal components for new anti-cancer drug is one of the main research activities throughout the world. According to low cost, oral consumption and easy access to the public extracts of Urtica dioica, in this study we aimed to investigate the effectiveness of this herb on MDA-MB-468 breast cancer cells.   Methods: Cytotoxic effect of Urtica dioica extract was measured using MTT assays. To show induction of apoptosis by this plant TUNEL and DNA Fragmentation test were performed.   Results: In the present study dichloromethane extracts noticeably killed cancer cells. IC50 values related to human breast adenocarcinoma cell line MDA-MB-468 were 29.46±1.05 µg/ml in 24 hours and 15.54±1.04 µg/ml in 48 hours. TUNEL test and DNA Fragmentation assay showed apoptotic characteristic in the extract treated cells.   Conclusion: The results showed that MDA-MB-468 cells after treatment with dichloromethane extract of Urtica dioica, induces apoptosis in MDA-MB-468 cancer cells which may be useful in the treatment of cancer.

Experiment list: SRX099864 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ction=Pleura|Tissue Diagnosis=Adenocarcinoma 25775296,94.5,18.3,57005 GSM808753: MCF7 CTCF REP2 source_name=breast adenocarcinoma... cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibody=CTCF http

Experiment list: SRX099863 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ction=Pleura|Tissue Diagnosis=Adenocarcinoma 22593576,94.8,16.6,51049 GSM808752: MCF7 CTCF REP1 source_name=breast adenocarcinoma... cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibody=CTCF http

SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung adenocarcinoma

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Huang W

2017-06-01

Full Text Available Weiyi Huang,* Haihua Huang,* Lei Wang, Jiong Hu, Weifeng Song Department of Oncology, The First People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Cytoskeleton is critical for carcinoma cell proliferation, migration, and invasion. Sad-1 and UNC-84 domain containing 1 (SUN1 is one of the core linkers of nucleoskeleton and cytoskeleton. However, the functions of SUN1 in lung adenocarcinoma are largely unknown.Methods: In this study, we first transduced the lentivirus delivering the short hairpin RNA (shRNA against SUN1 to lung adenocarcinoma cells (A549 and 95D cells with high efficiency. After lentivirus infection, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expressions of SUN1 mRNA and protein. The cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively. The cell distribution in the cell cycle was analyzed by flow cytometry.Results: Both mRNA and protein levels of SUN1 were significantly decreased in A549 and 95D cells after lentivirus infection, as indicated by quantitative real-time polymerase chain reaction and Western blot. Next, we found that cell proliferation and colony formation were markedly reduced in SUN1 silenced cells. Moreover, suppression of SUN1 led to cell cycle arrest at G0/G1 phase. Furthermore, Cyclin D1, CDK6, and CDK2 expressions were obviously reduced in A549 cells after SUN1 silencing.Conclusion: These results suggest that SUN1 plays an essential role in proliferation of lung adenocarcinoma cells in vitro and may be used as a potential therapeutic target for the treatment of lung adenocarcinoma in the future. Keywords: SUN1, lung cancer, proliferation

Follistatin is a novel biomarker for lung adenocarcinoma in humans.

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Fangfang Chen

Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

Experiment list: SRX099866 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available tion=Pleura|Tissue Diagnosis=Adenocarcinoma 52920745,93.0,40.4,27135 GSM808755: MCF7 cMYC REP2 source_name=breast adenocarcinoma... cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibody=cMYC http:

Experiment list: SRX099865 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available tion=Pleura|Tissue Diagnosis=Adenocarcinoma 48518944,65.7,26.5,32221 GSM808754: MCF7 cMYC REP1 source_name=breast adenocarcinoma... cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibody=cMYC http:

[Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

Science.gov (United States)

Li, Hao; Li, Songyan; Hu, Shidong; Zou, Guijun; Hu, Zilong; Wei, Huahua; Wang, Yufeng; Du, Xiaohui

2017-01-01

Objective To detect the frequencies of peripheral programmed death-1 + (PD-1 + ) lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells were detected using flow cytometry. Results The number of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in the peripheral blood.

Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma.

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Shi, Run; Sun, Qi; Sun, Jing; Wang, Xin; Xia, Wenjie; Dong, Gaochao; Wang, Anpeng; Jiang, Feng; Xu, Lin

2017-03-01

The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer. Cell division cycle 20 expression was significantly correlated with sex (p = 0.003), histological classification (p overexpression of cell division cycle 20 was significantly associated with bigger primary tumor size (p = 0.0023), higher MKI67 level (r = 0.7618, p Overexpression of cell division cycle 20 is associated with poor prognosis in lung adenocarcinoma patients, and its overexpression can also be used to identify high-risk groups. In conclusion, cell division cycle 20 might serve as a potential biomarker for lung adenocarcinoma patients.

Multisystem Langerhans cell histiocytosis coexisting with metastasizing adenocarcinoma of the lung: A case report

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Lovrenski Aleksandra

2013-01-01

Full Text Available Introduction. Langerhans cell histiocytosis (LCH is an uncommon disease of unknown etiology characterized by uncontrolled proliferation and infiltration of various organs by Langerhans cells. Case report. We presented a 54-year-old man, heavy smoker, with dyspnea, cough, hemoptysis, headache and ataxia, who died shortly after admission to our hospital. On the autopsy, tumor was found in the posterior segment of the right upper pulmonary lobe as well as a right-sided occipitoparietal lesion which penetrated into the right ventricle resulting in internal and external hematocephalus. Histologically and immunohistohemically, the diagnosis of primary lung adenocarcinoma with brain metastasis was made (tumor cells showed positivity for CK7 and TTF-1 which confirmed the diagnosis. In the lung parenchyma around the tumor, as well as in brain tissue around the metastatic adenocarcinoma histiocytic lesions were found. Light microscopic examination of the other organs also showed histiocytic lesions involving the pituitary gland, hypothalamus, spleen and mediastinal lymph nodes. Immunohistochemical studies revealed CD68, S-100 and CD1a immunoreactivity within the histiocytes upon which the diagnosis of Langerhans' cells histiocytosis was made. Conclusion. The multisystem form of LCH with extensive organ involvement was an incidental finding, while metastatic lung adenocarcinoma to the brain that led to hematocephalus was the cause of death.

Cytotoxic Effects and Anti-Angiogenesis Potential of Pistachio (Pistacia vera L.) Hulls against MCF-7 Human Breast Cancer Cells.

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Seifaddinipour, Maryam; Farghadani, Reyhaneh; Namvar, Farideh; Mohamad, Jamaludin; Abdul Kadir, Habsah

2018-01-05

Pistachio ( Pistacia vera L.) hulls (PVLH) represents a significant by-product of industrial pistachio processing that contains high amounta of phenolic and flavonoid compounds known to act as antioxidants. The current study was designed to evaluate the anti-tumor and anti-angiogenic potentials of PVLH extracts. The cytotoxic effects of hexane, ethyl acetate, methanol, and water PVLH extracts toward human colon cancer (HT-29 and HCT-116), breast adenocarcinoma (MCF-7), lung adenocarcinoma (H23), liver hepatocellular carcinoma (HepG2), cervical cancer (Ca Ski), and normal fibroblast (BJ-5ta) cells were assessed using a MTT cell viability assay. Apoptosis induction was evaluated through the different nuclear staining assays and confirmed by flow cytometry analysis. Anti-angiogenic activities were also determined using chorioallantoic membrane (CAM) assay. PVLH ethyl acetate extracts (PVLH-EAE) demonstrated a suppressive effect with an IC 50 value of 21.20 ± 1.35, 23.00 ± 1.2 and 25.15 ± 1.85 µg/mL against MCF-7, HT-29 and HCT-116, respectively, after 72 h of treatment. Morphological assessment and flow cytometry analysis showed the potential of PVLH-EAE to induce apoptosis. PVLH-EAE at the highest concentration demonstrated significant inhibition of angiogenesis as comparing with control group. Also the expression of Bax increased and the expression of Bcl-2 decreased in treated MCF-7 cells. Thus, the apoptosis induction and angiogenesis potential of PVLH-EAE make it to be the most suitable for further cancer research study to deal with selective antitumor active substances to human cancers especially breast cancer.

Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

LENUS (Irish Health Repository)

Beddy, P

2012-02-01

BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways.

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Siriwarin, Boondaree; Weerapreeyakul, Natthida

2016-07-25

Sesamol is a phenolic lignan found in sesame seeds (Sesamum indicum L.) and sesame oil. The anticancer effects and molecular mechanisms underlying its apoptosis-inducing effect were investigated in human lung adenocarcinoma (SK-LU-1) cells. Sesamol inhibited SK-LU-1 cell growth with an IC50 value of 2.7 mM and exhibited less toxicity toward normal Vero cells after 48 h of treatment (Selective index = 3). Apoptotic bodies-the hallmark of apoptosis-were observed in sesamol-treated SK-LU-1 cells, stained with DAPI. Sesamol increased the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol caused the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction. Decreasing Bid expression revealed crosstalk between the intrinsic and extrinsic apoptotic pathways; demonstrating clearly that sesamol induces apoptosis through both pathways in human lung adenocarcinoma (SK-LU-1) cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cytoplasmic Overexpression of CD95L in Esophageal Adenocarcinoma Cells Overcomes Resistance to CD95-Mediated Apoptosis

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Gregory A. Watson

2011-03-01

Full Text Available Introduction: The CD95/CD95L pathway plays a critical role in tissue homeostasis and immune system regulation; however, the function of this pathway in malignancy remains poorly understood. We hypothesized that CD95L expression in esophageal adenocarcinoma confers advantages to the neoplasm other than immune privilege. Methods: CD95L expression was characterized in immortalized squamous esophagus (HET-1A and Barrett esophagus (BAR-T cells; adenocarcinoma cell lines FLO-1, SEG-1, and BIC-1, and MDA468 (- control; and KFL cells (+ control. Analyses included reverse transcription-polymerase chain reaction, immunoblots of whole cell and secretory vesicle lysates, FACScan analysis, laser scanning confocal microscopy of native proteins and fluorescent constructs, and assessment of apoptosis and ERK1/2 pathways. Results: Cleaved, soluble CD95L is expressed at both the RNA and protein levels in these cell lines derived from esophageal adenocarcinoma and other human tissues. CD95L was neither trafficked to the cell membrane nor secreted into the media or within vesicles, rather the protein seems to be sequestered in the cytoplasm. CD95 and CD95L colocalize by immunofluorescence, but an interaction was not proven by immunoprecipitation. Overexpression of CD95L in the adenocarcinoma cell lines induced robust apoptosis and, under conditions of pan-caspase inhibition, resulted in activation of ERK signaling. Conclusions: CD95L localization in EA cells is inconsistent with the conference of immune privilege and is more consistent with a function that promotes tumor growth through alternative CD95 signaling. Reduced cell surface expression of CD95 affects cell sensitivity to extracellular apoptotic signals more significantly than alterations in downstream modulators of apoptosis.

SPRY4-mediated ERK1/2 signaling inhibition abolishes 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

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Li, Mingjiang; Zhang, Hui; Zhao, Xingbo; Yan, Lei; Wang, Chong; Li, Chunyan; Li, Changzhong

2014-08-01

Basic fibroblast growth factor (FGF2)-mediated Extracellular signal-regulated kinases1/2 (ERK1/2) signaling is a critical modulator in angiogenesis. SPRY4 has been reported to be a feedback negative regulator of FGFs-induced ERK1/2 signaling. The aim of this study was to explore the role of SPRY4 in endometrial adenocarcinoma cell. The effect of SPRY4 expression on FGF2-mediated ERK1/2 signaling was detected by luciferase assay and Western blot analysis. The growth of Ishikawa cells was detected using colony formation assay and cell number counting experiment. We found that plasmid-driven SPRY4 expression efficiently blocked the activity of FGF2-induced ERK1/2 signaling in Ishikawa cells. SPRY4 expression significantly reduced the proliferation and 17β-estradiol-induced proliferation of Ishikawa cells. SPRY4 may function as a tumor suppressor in endometrial adenocarcinoma.

Evaluation of chemopreventive and cytotoxic effect of lemon seed extracts on human breast cancer (MCF-7) cells.

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Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Uckoo, Ram M; Patil, Bhimanagouda S

2012-02-01

Extracts from lemon seed were investigated for the radical scavenging activity and apoptotic effects in human breast adenocarcinoma (MCF-7) cells and non-malignant breast (MCF-12F) cells for the first time. Defatted seed powder was successively extracted with ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20). The chemical constituents were identified and quantified by LC-MS and HPLC analysis, respectively. The highest radical scavenging activity of 62.2% and 91.3% was exhibited by MeOH:water (80:20) at 833μg/mL in 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(+)), respectively. In addition, the MeOH:water (80:20) extract showed the highest (29.1%, Pwater (80:20) extract induced DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Increased levels of Bax and cytosolic cytochrome C and decreased levels of Bcl2 were also observed in MeOH:water (80:20) treated MCF-7 cells. In conclusion, the MeOH:water (80:20) extract from lemon seed has potent antioxidant activity and induces apoptosis in MCF-7 cells, leading to the inhibition of proliferation. These results suggest that aglycones and glucosides of the limonoids and flavonoid present in MeOH:water (80:20) extract may potentially serve as a chemopreventive agent for breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells.

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Shen, Kaikai; Xie, Jianling; Wang, Hua; Zhang, Hong; Yu, Mengyuan; Lu, Fangfang; Tan, Hongsheng; Xu, Hongxi

2015-07-01

Cambogin is a polycyclic polyprenylated acylphoroglucinol (PPAP) from the Garcinia genus, which has been used traditionally for cancer treatment across Southeastern Asia. In this study, we found that cambogin inhibited breast cancer cell proliferation and induced cell apoptosis in vitro. Cambogin induced the activation of the caspase-independent mitochondrial apoptotic pathway, as indicated by an increase in the ratio of Bax/Bcl-2 and the nuclear translocation of apoptosis inducing factor (AIF). Two-dimensional gel electrophoresis and mass spectrometry revealed that the expression of proteins involving in the radical oxygen species (ROS) pathway was among the most affected upon cambogin treatment. Cambogin enhanced cellular ROS production, and induced the activation of the ASK1-MKK4/MKK7-JNK/SAPK signaling pathway. Pretreatment with ROS scavenger N-acetylcysteine (NAC), an antioxidant, or the JNK inhibitor SP600125 was able to restore cell viability in the presence of cambogin. Importantly, cambogin treatment led to the activation of activating transcription factor-2 (ATF-2) and the trimethylation of histone H3K9 in the activator protein 1 (AP-1) binding region of the Bcl-2 gene promoter. Finally, cambogin exhibited a potential antitumor effect in MCF-7 breast cancer xenografts without apparent toxicity. Taken in conjunction, the present study indicates that cambogin can induce breast adenocarcinoma cell apoptosis and therefore represents therapeutic potential for cancer treatment. ©2015 American Association for Cancer Research.

Exogenous wild type p53 gene affects radiosensitivity of human lung adenocarcinoma cell line under hypoxia

International Nuclear Information System (INIS)

Wang Jianhua; Wang Feng; Liu Yongping; Zhang Yaping; Ni Yan; Li Shirong

2008-01-01

Objective: To evaluate the effect of exogenous wild type p53 (wtp53) gene on radiosensitivity of human lung adenocarcinoma cell line under hypoxia. Methods: Human lung adenocarcinoma cell line A549 was transfected with adenovirus carrying recombinant exogenous wtp53. Four irradiation groups were studied: normal cell (Group A), wtp53 transfected cell (Group B), normal cell under hypoxia (Group C) and wtp53 transfected cell under hypoxia(Group D). Cells were irradiated with 9 MeV electron beams. Cellular survival fraction was analyzed. Multi-target single-hit model was used to plot the survival curve. D 0 , D q , oxygen enhancement ratio (OER), sensitizing enhancement ratio (SER) and other parameters were used to evaluate the effects of wtp53 gene on radiosensitivity of A549. The cell apoptotic rate of each group was examined by flow cytometry. Results: OER was 1.75 and 0.81 before and after wtp53 transfection. SER was 1.77 in oxic circumstance and 3.84 under hypoxia. The cell apoptotic rate of Group A and B was lower than Group C and D (F=7.92, P=0.048), with Group A lower than B and Group C lower than D (F=82.50, P=0.001). But Group B and D were similar(t=2.04, P=0.111). Conclusions: Hypoxia can increase the radiation resistance of lung adenocarcinoma cell line A549. The wtp53 can promote apoptosis and improve tumor radiosensitivity, especially under hypoxia. (authors)

Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

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John Wysocki

2014-01-01

Full Text Available Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC. Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas.

Growth suppression of MCF-7 cancer cell-derived xenografts in nude mice by caveolin-1

International Nuclear Information System (INIS)

Wu Ping; Wang Xiaohui; Li Fei; Qi Baoju; Zhu Hua; Liu Shuang; Cui Yeqing; Chen Jianwen

2008-01-01

Caveolin-1 is an essential structural constituent of caveolae membrane domains that has been implicated in mitogenic signaling and oncogenesis. However, the exact functional role of caveolin-1 still remains controversial. In this report, utilizing MCF-7 human breast adenocarcinoma cells stably transfected with caveolin-1 (MCF-7/cav-1 cells), we demonstrate that caveolin-1 expression dramatically inhibits invasion and migration of these cells. Importantly, in vivo experiments employing xenograft tumor models demonstrated that expression of caveolin-1 results in significant growth inhibition of breast tumors. Moreover, a dramatic delay in tumor progression was observed in MCF-7/cav-1 cells as compared with MCF-7 cells. Histological analysis of tumor sections demonstrated a marked decrease in the percentage of proliferating tumor cells (Ki-67 assay) along with an increase in apoptotic tumor cells (TUNEL assay) in MCF-7/cav-1-treated animals. Our current findings provide for the first time in vivo evidence that caveolin-1 can indeed function as a tumor suppressor in human breast adenocarcinoma derived from MCF-7 cells rather than as a tumor promoter

STMN-1 is a potential marker of lymph node metastasis in distal esophageal adenocarcinomas and silencing its expression can reverse malignant phenotype of tumor cells

International Nuclear Information System (INIS)

Akhtar, Javed; Wang, Zhou; Yu, Che; Li, Chen-Sheng; Shi, Yu-Long; Liu, Hong-Jun

2014-01-01

Distal esophageal adenocarcinoma is a highly aggressive neoplasm. Despite advances in diagnosis and therapy, the prognosis is still poor. Stathmin (STMN-1) is a ubiquitously expressed microtubule destabilizing phosphoprotein. It promotes the disassembly of microtubules and prevents assembly. STMN-1 can cause uncontrolled cell proliferation when mutated and not functioning properly. Recently, found to be overexpressed in many types of human cancers. However, its clinical significance remains elusive in distal esophageal adenocarcinoma. Here, we reported for the first time that STMN-1 is highly overexpressed in adenocarcinomas of the distal esophagus and strongly associated with lymph node metastasis. STMN-1 expression in 63 cases of distal esophageal adenocarcinoma was analyzed by immunoblotting, while expression in esophageal adenocarcinoma cells was determined by immunocytochemistry, immunofluorescence, qRT-PCR and western blotting. Lentivirus-mediated RNAi was employed to knock-down STMN-1 expression in Human esophageal adenocarcinoma cells. The relationship between STMN-1 expression and lymph node metastasis in distal esophageal adenocarcinoma was determined by univariate and multivariate analyses. STMN-1 was detected in 31 (49.21%) of the 63 cases. STMN-1 was highly overexpressed in specimens with lymph node metastasis pN (+), but its expression was almost undetected in pN (−) status. Multivarian regression analysis demonstrated that STMN-1 overexpression is an independent factor for lymph node metastasis in distal esophageal adenocarcinoma. STMN-1 shRNA effectively reduced STMN-1 expression in esophageal adenocarcinoma cells (P < 0.05), which significantly suppressed proliferation (P < 0.05), increased migration (P < 0.05) and invasion ability (P < 0.05) and G1 phase arrest (P < 0.05) which lead to induction of apoptosis in esophageal adenocarcinoma cells in vitro. To verify the in vitro data, we conducted in vivo tumor xenograft studies. Esophageal

Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: Morphologic and immunohistochemical findings and differential diagnosis

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Pei-Wen Huang

2015-01-01

Full Text Available Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms′ tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result.

Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.

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Baiwen Li

Full Text Available Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

DEFF Research Database (Denmark)

Schnack, Tine H; Høgdall, Estrid; Thomsen, Lotte Nedergaard

2017-01-01

OBJECTIVES: Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according...... to endometriosis status. METHODS: Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic...... regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. RESULTS: Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher...

Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure

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Sahbaie Peyman

2007-06-01

Full Text Available Abstract Background Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation. Methods Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment. Results The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure. Conclusion Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.

Experiment list: SRX185907 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Homo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, control, FOXM1 ChIP || cell_line=MCF-...7 || cell_type=ER-positive breast adenocarcinoma cells || treatment=DMSO || chip_

Clear cell adenocarcinoma of the ulterine cervix in a 15 year old girl: A case report

International Nuclear Information System (INIS)

Choi, Seung Joon; Kim, Jee Eun; KIm, Hyung Sik; Choi, Hye Young

2013-01-01

Cervical cancer is rare in the pediatric population. In cases of cervical cancer, adenocarcinoma is predominantly reported. Clear cell adenocarcinoma (CCAC) of the uterine cervix is a very rare tumor and accounts for only 4% of all adenocarcinomas of the uterine cervix. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor. This study reports the imaging finding of primary uterine cervical tumor in a 15-year-old girl, who was finally diagnosed with CCAC, with no maternal history of DES exposure in utero.

Clear cell adenocarcinoma of the ulterine cervix in a 15 year old girl: A case report

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Choi, Seung Joon; Kim, Jee Eun; KIm, Hyung Sik; Choi, Hye Young [Dept. of Radiology, Gachon University Gil Hospital, Incheon (Korea, Republic of)

2013-10-15

Cervical cancer is rare in the pediatric population. In cases of cervical cancer, adenocarcinoma is predominantly reported. Clear cell adenocarcinoma (CCAC) of the uterine cervix is a very rare tumor and accounts for only 4% of all adenocarcinomas of the uterine cervix. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor. This study reports the imaging finding of primary uterine cervical tumor in a 15-year-old girl, who was finally diagnosed with CCAC, with no maternal history of DES exposure in utero.

Methanolic Extracts from Brown Seaweeds Dictyota cilliolata and Dictyota menstrualis Induce Apoptosis in Human Cervical Adenocarcinoma HeLa Cells

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Dayanne Lopes Gomes

2015-04-01

Full Text Available Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer agents. Here, methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta and Chlorophyta collected from the Northeast of Brazil were assessed as apoptosis-inducing agents on human cervical adenocarcinoma (HeLa. All extracts showed different levels of cytotoxicity against HeLa cells; the most potent were obtained from the brown alga Dictyota cilliolata (MEDC and Dictyota menstrualis (MEDM. In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma cell proliferation. Studies with these two extracts using flow cytometry and fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit morphological and biochemical changes that characterize apoptosis as shown by loss of cell viability, chromatin condensation, phosphatidylserine externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9 by these extracts suggests a mitochondria-dependent apoptosis route. However, other routes cannot be ruled out. Together, these results point out the methanol extracts of the brown algae D. mentrualis and D. cilliolata as potential sources of molecules with antitumor activity.

Experiment list: SRX185915 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available mo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, control, FOXM1 ChIP || cell_line=MCF-7 |...| cell_type=ER-positive breast adenocarcinoma cells || treatment=DMSO || chip_tar

Experiment list: SRX185909 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available omo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, control, FOXM1 ChIP || cell_line=MCF-7 ...|| cell_type=ER-positive breast adenocarcinoma cells || treatment=DMSO || chip_ta

Experiment list: SRX185917 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available omo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, control, FOXM1 ChIP || cell_line=MCF-7 ...|| cell_type=ER-positive breast adenocarcinoma cells || treatment=DMSO || chip_ta

Experiment list: SRX185916 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available on 4; Homo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, thiostrepton, FOXM1 ChIP || cell..._line=MCF-7 || cell_type=ER-positive breast adenocarcinoma cells || treatment=thi

Assessment of cytotoxicity of Portulaca oleracea Linn. against human colon adenocarcinoma and vero cell line

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Mali, Prashant Y.

2015-01-01

Background: Portulaca oleracea Linn. (Portulacaceae) is commonly known as purslane in English. In traditional system it is used to cure diarrhea, dysentery, leprosy, ulcers, asthma, and piles, reduce small tumors and inflammations. Aim: To assess cytotoxic potential of chloroform extract of P. oleracea whole plant against human colon adenocarcinoma (HCT-15) and normal (Vero) cell line. Materials and Methods: Characterization of chloroform extract of P. oleracea by Fourier transform infrared (FTIR) spectroscopy was performed. Cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was used for assessment of cytotoxic potential of chloroform extract of P. oleracea. The concentrations of 1000–0.05 μg/ml were used in the experiment. Doxorubicin was considered as standard reference drug. Results: FTIR spectrum showed the peak at 1019.52 and 1396.21 center. The 50% cell growth inhibition (IC50) of chloroform extract of P. oleracea and doxorubicin was 1132.02 μg/ml and 460.13 μg/ml against human colon adenocarcinoma and 767.60 μg/ml and 2392.71 μg/ml against Vero cell line, respectively. Conclusion: Chloroform extract of P. oleracea whole plant was less efficient or does not have cytotoxic activity against human colon adenocarcinoma cell line. It was not safe to normal Vero cell line. But, there is a need to isolate, identify, and confirm the phytoconstituents present in extract by sophisticated analytical techniques. PMID:27833374

Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

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Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

2016-01-01

Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

International Nuclear Information System (INIS)

Wu, Qiang; Kong, Xiang-jun; Xu, Xiao-chun; Lobie, Peter E; Zhu, Tao; Wu, Zheng-sheng; Liu, Xue; Yan, Hong; He, Yin-huan; Ye, Shan; Cheng, Xing-wang; Zhu, Gui-lu; Wu, Wen-yong; Wang, Xiao-nan

2014-01-01

B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer

Cytomorphologic features of papillary lesions of the male breast: a study of 11 cases.

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Reid-Nicholson, Michelle D; Tong, Guoxia; Cangiarella, Joan F; Moreira, Andre L

2006-08-25

Breast masses occur in men far less commonly than women and are infrequently subjected to fine-needle aspiration (FNA) biopsy. Papillary lesions of the male breast are rare and are comprised of a spectrum of lesions ranging from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. The following study describes the cytomorphology of papillary breast lesions in 11 men. The patients ranged in age from 23 to 78 years old and each presented with an unilateral subareolar or periareolar breast mass that varied in size from 0.5 to 3 cm. Two patients presented with bloody nipple discharge. Archival material (8-year period) from FNA biopsies of papillary lesions of the male breast was reviewed. The reviewed cases were correlated with appropriate clinicopathologic follow-up. The smears had variable cellularity but all showed papillary clusters of mammary epithelial cells with and without fibrovascular cores. Single epithelial cells with a high nuclear-to-cytoplasmic ratio and eccentric nuclei were seen in all smears; however, these were more numerous in cases of adenocarcinoma. Hemosiderin-laden macrophages were present in all cases. Nipple discharge was seen only in the 2 benign lesions. All adenocarcinomas occurred in older men. The only cytologic criteria that differentiated benign from malignant papillary lesions were marked cellularity and the presence of abundant 3-dimensional clusters. To the best of the authors' knowledge, the current series is the largest in the English literature to date that examines the cytomorphologic features of papillary breast lesions in men. Copyright 2006 American Cancer Society.

Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer.

Science.gov (United States)

Mukherjee, Pinku; Madsen, Cathy S; Ginardi, Amelia R; Tinder, Teresa L; Jacobs, Fred; Parker, Joanne; Agrawal, Babita; Longenecker, B Michael; Gendler, Sandra J

2003-01-01

Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in 90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach, colon, and ovary. MUC1 is a target for immune intervention, because, in patients with solid adenocarcinomas, low-level cellular and humoral immune responses to MUC1 have been observed, which are not sufficiently strong to eradicate the growing tumor. The hypothesis for this study is that enhancing MUC1-specific immunity will result in antitumor immunity. To test this, the authors have developed a clinically relevant breast cancer model that demonstrates peripheral and central tolerance to MUC1 and develops spontaneous tumors of the mammary gland. In these mice, the authors tested a vaccine formulation comprised of liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate that when compared with untreated mice, immunized mice develop T cells that express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1 tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The presence of MUC1-specific CTL did not translate into a clinical response as measured by time of tumor onset, tumor burden, and survival. The authors demonstrate that some of the immune-evasion mechanisms used by the tumor cells include downregulation of MHC-class I molecule, expression of TGF-beta2, and decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally, utilizing an injectable breast cancer model, the authors show that targeting a single tumor antigen may not be an effective antitumor treatment, but that immunization with dendritic cells fed with whole tumor lysate is effective in breaking tolerance and protecting mice from subsequent tumor challenge. A physiologically relevant spontaneous breast cancer model has been developed to test improved immunotherapeutic approaches.

Leser–Trélat syndrome in malignant mesothelioma and pulmonary adenocarcinoma

DEFF Research Database (Denmark)

Jepsen, Rikke Karlin; Skov, Anne Guldhammer; Skov, Birgit Guldhammer

2014-01-01

The syndrome of Leser–Trélat (LT) is characterized by the sudden appearance of multiple seborrhoeic keratoses (SKs) in association with internal occult malignancy. Usually, the syndrome has been associated with adenocarcinoma, most frequently of the gastrointestinal tract and breast. The pathogen...

The Human Cell Surfaceome of Breast Tumors

Science.gov (United States)

da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

2013-01-01

Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors. PMID:24195083

Stem cells in the human breast

DEFF Research Database (Denmark)

Petersen, Ole William; Polyak, Kornelia

2010-01-01

The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry.

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Renault, Anne-Laure; Lesueur, Fabienne; Coulombe, Yan; Gobeil, Stéphane; Soucy, Penny; Hamdi, Yosr; Desjardins, Sylvie; Le Calvez-Kelm, Florence; Vallée, Maxime; Voegele, Catherine; Hopper, John L; Andrulis, Irene L; Southey, Melissa C; John, Esther M; Masson, Jean-Yves; Tavtigian, Sean V; Simard, Jacques

2016-01-01

Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer.

BITC Sensitizes Pancreatic Adenocarcinomas to TRAIL-induced Apoptosis

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Christina A. Wicker

2009-01-01

Full Text Available Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12, which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC. BITC is a component of cruciferous vegetables and a cell cycle inhibitor. BxPC3, MiaPaCa2 and Panc-1 human pancreatic adenocarcinoma cell lines were examined for TRAIL resistance. Our studies show BITC induced TRAIL sensitization by dual activation of both the extrinsic and intrinsic apoptotic pathways.

Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

DEFF Research Database (Denmark)

Jacobsen, Benedikte; Santoni-Rugiu, Eric; Illemann, Martin

2012-01-01

in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased...... in squamous metaplasia. This was confined to the cell membrane and sustained in dysplasia, carcinoma in situ, and the invasive carcinoma. The induction of C4.4A already at the stage of hyperplasia could indicate that it is a marker of very early squamous differentiation, which aligns well with our earlier...... finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical...

Experiment list: SRX185908 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available epton 1; Homo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, thiostrepton, FOXM1 ChIP || c...ell_line=MCF-7 || cell_type=ER-positive breast adenocarcinoma cells || treatment=

Endothelial induced EMT in breast epithelial cells with stem cell properties.

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Valgardur Sigurdsson

Full Text Available Epithelial to mesenchymal transition (EMT is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad to N-Cadherin (N-Cad and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high/CD24(low ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer.

Endothelial induced EMT in breast epithelial cells with stem cell properties.

Science.gov (United States)

Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla; Fridriksdottir, Agla J R; Ringnér, Markus; Villadsen, Rene; Borg, Ake; Agnarsson, Bjarni A; Petersen, Ole William; Magnusson, Magnus K; Gudjonsson, Thorarinn

2011-01-01

Epithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer.

T cell recognition of breast cancer antigens

DEFF Research Database (Denmark)

Petersen, Nadia Viborg; Andersen, Sofie Ramskov; Andersen, Rikke Sick

Recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability ofimmunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described, thus it is necessary to identify T cell targets to develop immune mediated therapies.......This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, NEK3, and PIAS3 contribute to increase growth, survival, and motility of malignant cells. Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse...... recognition utilizing DNA barcode labeled MHC multimers to screen peripheral blood lymphocytes from breast cancer patients and healthy donor samples. Signif-icantly more TAA specific T cell responses were detected in breast cancer patients than healthy donors for both HLA-A*0201 (P

Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

Science.gov (United States)

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells.

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Yi-Jyun Liu

Full Text Available Lung cancer is the leading cause of cancer-related mortality worldwide. Radiotherapy is often applied for treating lung cancer, but it often fails because of the relative non-susceptibility of lung cancer cells to radiation. MicroRNAs (miRNAs have been reported to modulate the radiosensitivity of lung cancer cells and have the potential to improve the efficacy of radiotherapy. The purpose of this study was to identify a miRNA that can adjust radiosensitivity in lung adenocarcinoma cells. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5 with different metastatic ability and radiosensitivity were used. In order to understand the regulatory mechanisms of differential radiosensitivity in these isogenic tumor cells, both CL1-0 and CL1-5 were treated with 10 Gy radiation, and were harvested respectively at 0, 1, 4, and 24 h after radiation exposure. The changes in expression of miRNA upon irradiation were examined using Illumina Human microRNA BeadChips. Twenty-six miRNAs were identified as having differential expression post-irradiation in CL1-0 or CL1-5 cells. Among these miRNAs, miR-449a, which was down-regulated in CL1-0 cells at 24 h after irradiation, was chosen for further investigation. Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation.

Experiment list: SRX185910 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ton 2; Homo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, thiostrepton, FOXM1 ChIP || cel...l_line=MCF-7 || cell_type=ER-positive breast adenocarcinoma cells || treatment=th

Experiment list: SRX185918 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ton 7; Homo sapiens; ChIP-Seq source_name=MCF-7 breast adenocarcinoma cells, thiostrepton, FOXM1 ChIP || cel...l_line=MCF-7 || cell_type=ER-positive breast adenocarcinoma cells || treatment=th

Experiment list: SRX099867 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available arcinoma cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibo...Site of Extraction=Pleura|Tissue Diagnosis=Adenocarcinoma 30298258,97.7,6.0,12863 GSM808756: MCF7 Pol2 REP1 source_name=breast adenoc

Experiment list: SRX099868 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available arcinoma cells || cell type=breast adenocarcinoma cells || cell line=MCF7 || antibo...Site of Extraction=Pleura|Tissue Diagnosis=Adenocarcinoma 29604416,97.2,9.0,21453 GSM808757: MCF7 Pol2 REP2 source_name=breast adenoc

LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

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Islas-Vazquez, Lorenzo; Aguilar-Cazares, Dolores; Meneses-Flores, Manuel; Galicia-Velasco, Miriam; Romero-Garcia, Susana; Camacho-Mendoza, Catalina; Lopez-Gonzalez, Jose Sullivan

2015-01-01

Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP) TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells. PMID:26582240

LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

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Lorenzo Islas-Vazquez

2015-01-01

Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

Prostatic Adenocarcinoma with Concurrent Sertoli Cell Tumor in a Dog

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Gill, C. W.

1981-01-01

A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7340923

Echinophora platyloba DC (Apiaceae crude extract induces apoptosis in human prostate adenocarcinoma cells (PC 3

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Fatemeh Zare Shahneh

2014-10-01

Full Text Available Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line. Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end labeling (TUNEL assay and DNA fragmentation gel electrophoresis. Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml. Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis

Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Hara, Takamitsu [Gunma Prefectural College of Health Sciences, Department of Radiological Technology, School of Radiological Technology, Gunma, Maebashi (Japan); Iwadate, Manabu [Fukushima Medical University, Department of Thyroid and Endocrinology, School of Medicine, Fukushima (Japan); Tachibana, Kazunoshin [Fukushima Medical University, Department of Breast Surgery, School of Medicine, Fukushima (Japan); Waguri, Satoshi [Fukushima Medical University, Department of Anatomy and Histology, School of Medicine, Fukushima (Japan); Takenoshita, Seiichi [Fukushima Medical University, Advanced Clinical Research Center, Fukushima Global Medical Science Center, School of Medicine, Fukushima (Japan); Hamada, Nobuyuki [Central Research Institute of Electric Power Industry (CRIEPI), Radiation Safety Research Center, Nuclear Technology Research Laboratory, Tokyo, Komae (Japan)

2017-10-15

Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X-ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance. (orig.) [German] Metastasierung ist die Hauptursache fuer den toedlichen Verlauf von Brustkrebserkrankungen. Darauf muessen spezifische Behandlungsstrategien ausgerichtet werden. Sowohl primaere als auch metastatische Brustkrebsarten koennen mit einer Strahlentherapie behandelt werden, allerdings sind die Unterschiede in der Reaktion auf ionisierende Strahlung bis heute nicht vollstaendig verstanden. In dieser Studie wird zum ersten Mal die Strahlenantwort einer Brustkrebszelllinie mit der ihrer metastatischen Varianten verglichen und die erhoehte Strahlenresistenz der metastatischen Varianten gezeigt. Eine Luciferase-exprimierende Zelllinie wurde aus humanen basaloiden Brustadenokarzinomen

Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells.

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Kuznetsov, Hanna S; Marsh, Timothy; Markens, Beth A; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A; Brown, Victoria E; Richardson, Andrea L; Signoretti, Sabina; Battinelli, Elisabeth M; McAllister, Sandra S

2012-12-01

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC "instigators") establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors ("responders"). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2(+) tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. ©2012 AACR.

A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature

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Zhang C

2016-09-01

Full Text Available Chengsheng Zhang,1,2 Wei Zhang,1,2 Dianbin Mu,1 Xuetao Shi,1 Lei Zhao1,2 1Department of Hepatobiliary Surgery, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, 2School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China Abstract: An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9 and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL, whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL. Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients. Keywords: gallbladder, clear cell adenocarcinoma, hepatoid differentiation 

Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

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2017-10-01

AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties which

Experiment list: SRX185912 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available MB-231 foxm1 Thiostrepton 1; Homo sapiens; ChIP-Seq source_name=MDA-MB-231 breast adenocarcinoma cells, thio...strepton, FOXM1 ChIP || cell_line=MDA-MB-231 || cell_type=ER-negative breast adenocarcinoma

Experiment list: SRX185911 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available B-231 foxm1 DMSO 1; Homo sapiens; ChIP-Seq source_name=MDA-MB-231 breast adenocarcinoma cells, control, FOXM...1 ChIP || cell_line=MDA-MB-231 || cell_type=ER-negative breast adenocarcinoma cel

Experiment list: SRX185914 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available B-231 foxm1 Thiostrepton 2; Homo sapiens; ChIP-Seq source_name=MDA-MB-231 breast adenocarcinoma cells, thios...trepton, FOXM1 ChIP || cell_line=MDA-MB-231 || cell_type=ER-negative breast adenocarcinoma

Clear Cell Adenocarcinoma of the Urethra: Review of the Literature

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Anthony Kodzo-Grey Venyo

2015-01-01

Full Text Available Background. Clear cell adenocarcinoma of the urethra (CCAU is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour. Aims. To review the literature on CCAU. Methods. Various internet databases were used. Results/Literature Review. (i CCAU occurs in adults and in women in the great majority of cases. (ii It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v CCAU is aggressive with low 5-year survival rates. (vi There is no consensus opinion of treatment options that would improve the prognosis. Conclusions. Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

International Nuclear Information System (INIS)

Gockel, Ines; Galle, Peter R; Junginger, Theodor; Moehler, Markus; Schimanski, Carl C; Heinrich, Christian; Wehler, T; Frerichs, K; Drescher, Daniel; Langsdorff, Christian von; Domeyer, Mario; Biesterfeld, Stefan

2006-01-01

Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both

The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment.

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Lundgren, Sebastian; Warfvinge, Carl Fredrik; Elebro, Jacob; Heby, Margareta; Nodin, Björn; Krzyzanowska, Agnieszka; Bjartell, Anders; Leandersson, Karin; Eberhard, Jakob; Jirström, Karin

2016-01-01

Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29-0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers.

Experiment list: SRX185913 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available MB-231 foxm1 DMSO 2; Homo sapiens; ChIP-Seq source_name=MDA-MB-231 breast adenocarcinoma cells, control, FOX...M1 ChIP || cell_line=MDA-MB-231 || cell_type=ER-negative breast adenocarcinoma ce

Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

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Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

2015-01-01

The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

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Christopher R S Banerji

2015-03-01

Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

ESOPHAGEAL CARCINOMA: IS SQUAMOUS CELL CARCINOMA DIFFERENT DISEASE COMPARED TO ADENOCARCINOMA? A transversal study in a quaternary high volume hospital in Brazil.

Science.gov (United States)

Tustumi, Francisco; Takeda, Flavio Roberto; Kimura, Cintia Mayumi Sakurai; Sallum, Rubens Antônio Aissar; Ribeiro, Ulysses; Cecconello, Ivan

2016-01-01

Esophageal cancer is one of the leading causes of mortality among the neoplasms that affect the gastrointestinal tract. There are several factors that contribute for development of an epidemiological esophageal cancer profile in a population. This study aims to describe both clinically and epidemiologically the population of patients with diagnosis of esophageal cancer treated in a quaternary attention institute for cancer from January, 2009 to December, 2011, in Sao Paulo, Brazil. The charts of all patients diagnosed with esophageal cancer from January, 2009, to December, 2011, in a Sao Paulo (Brazil) quaternary oncology institute were retrospectively reviewed. Squamous cell cancer made up to 80% of the cases of esophageal cancer. Average age at diagnosis was 60.66 years old for esophageal adenocarcinoma and 62 for squamous cell cancer, average time from the beginning of symptoms to the diagnosis was 3.52 months for esophageal adenocarcinoma and 4.2 months for squamous cell cancer. Average time for initiating treatment when esophageal cancer is diagnosed was 4 months for esophageal adenocarcinoma and 4.42 months for squamous cell cancer. There was a clear association between squamous cell cancer and head and neck cancers, as well as certain habits, such as smoking and alcoholism, while adenocarcinoma cancer showed more association with gastric cancer and gastroesophageal reflux disease. Tumoral bleeding and pneumonia were the main causes of death. No difference in survival rate was noted between the two groups. Adenocarcinoma and squamous cell carcinoma are different diseases, but both are diagnosed in advanced stages in Brazil, compromising the patients' possibilities of cure.

Kiss-1/GPR54 protein expression in breast cancer.

Science.gov (United States)

Papaoiconomou, Eleni; Lymperi, Maria; Petraki, Constantina; Philippou, Anastassios; Msaouel, Pavlos; Michalopoulou, Fani; Kafiri, Georgia; Vassilakos, George; Zografos, Georgios; Koutsilieris, Michael

2014-03-01

Numerous studies have shown that the Kiss-1 gene countervails the metastatic aptitude of several cancer cell lines and solid-tumor neoplasias. However, there still remains ambiguity regarding its role in breast cancer and literature has arisen asserting that Kiss-1 expression may be linked to an aggressive phenotype and malignant progression. Herein, we investigated the protein expression of Kiss-1 and its receptor GPR54 in breast cancer tissues compared to non-cancerous mammary tissues. Paraffin-fixed cancer tissues from 43 women with resected breast adenocarcinomas and 11 specimens derived from women suffering from fibrocystic disease, serving as controls, were immunostained with Kiss-1 and GPR54 antibodies. Kiss-1 and GPR54 protein expression levels were significantly higher in breast cancer compared to fibrocystic tissues (pbreast cancer and fibrocystic disease specimens. Kiss-1/GPR54 expression was found to be significantly higher in breast cancer compared to non-malignant mammary tissues.

Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice

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Shunfang YANG

2009-10-01

Full Text Available Background and objective The recurrence, metastasis and multidrug resistance (MDR in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. Methods The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. Results The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1×106 and 1.5×106 cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2. Conclusion The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it’s a good experimental

Metformin inhibits 17?-estradiol-induced epithelial-to-mesenchymal transition via ?Klotho-related ERK1/2 signaling and AMPK? signaling in endometrial adenocarcinoma cells

OpenAIRE

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-01-01

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17?-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17?-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17?-estradiol-induc...

Effect of repeated irradiation on biological characteristics of lung adenocarcinoma cell line Anip973 in vitro

International Nuclear Information System (INIS)

Xu Qingyong; Xu Xiangying; Yang Zhiwei

2008-01-01

Objective: To study the effect of repeated irradiation on biological characteristics of human lung adenocarcinoma cell line Anip973 in vitro. Methods: Anip973 cells were treated with high energy X-ray to a total dose of 60 Gy at 4 Gy fractions. The radiosensitivity of Anip973R and its parental cell were measured by clonogenic assay. The biological parameters were fitted to the single hit multitarget formula. Furthermore, the population double time(PDT) and cell cycle distribution were measured by cell growth curve and flow cytometry, respectively. Results: Comparing with its parental cell, Anip973 R acquired radioresistance showing increased D 0 , D q and SF 2 and a broader shoulder. PDT of Anip973R extended 3 h more than that of Anip973. The Anip973R also showed higher and lower percentage of cells in G 1 and S phase (P 2 /M distribution (P>0.05). Conclusions: A radioresistant lung adenocarcinoma cell line Anip973R is established by repeatedly irradiation. Its radioresistance displays obviously in lower dose area. However, its characteristic of cell cycle is not completely coincident with the classical radiobiological theory. (authors)

Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

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Magnusson Magnus K

2010-07-01

Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

5-Fluorouracil-radiation interactions in human colon adenocarcinoma cells

International Nuclear Information System (INIS)

Buchholz, Daniel J.; Lepek, Katherine J.; Rich, Tyvin A.; Murray, David

1995-01-01

Purpose: To determine the effect of cellular proliferation and cell cycle stage on the ability of postirradiation 5-fluorouracil (5-FU) to radiosensitize cultured human colon adenocarcinoma Clone A cells. Methods and Materials: Cell survival curves were generated for irradiated: (a) log- and plateau-phase Clone A cells; and (b) Clone A cells separated by centrifugal elutriation into the various phases of the cell cycle; with and without postirradiation treatment with 100 μg/ml 5-FU. Results: Postirradiation treatment with 5-FU sensitized proliferating cells to a greater degree than it sensitized cells growing in plateau phase. The β component of cell kill in log-phase cells was increased by a factor of 1.5 with a sensitizer enhancement ratio of 1.21 at the 0.01 survival level. Plateau-phase cells showed less radiosensitization (sensitizer enhancement ratio of 1.13 at the 0.01 survival level); however, there was a mild increase in both α and β kill in plateau-phase cells. Elutriated G 1 cells were the most radiosensitive, independent of treatment with 5-FU. The phase of the cell cycle had little effect on the ability of fluorouracil to radiosensitize Clone A cells. Conclusion: Proliferating cells are more susceptible to radiosensitization with 5-FU than plateau-phase cells are, but this effect appears to be independent of the phase of the cell cycle

Enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell with different p53 status

International Nuclear Information System (INIS)

Pang Dequan; Wang Peiguo; Wang Ping; Zhang Weiming

2008-01-01

Objective: To investigate the enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell lines(A549 and GLC-82) with different p53 status in vitro. Methods: Two human lung adenocarcinoma cell lines of A549 and GLC-82 were examined on their difference in p53 status with immunohistochemistry stain and PCR-SSCP technique. Expand Ad-wtp53 was transfected into tumor cells. Clonogenic assays were performed to evaluate the inhibition effect on cell growth and the degree of sensitization to irradiation. Apoptosis and cell cycle changes were determined using the flow cytometry assay. Results: The A549 cell line presented positive P53 expression while GLC-82 negative. GLC-82 bore mutant p53 on the exon 7. The wtp53 gene could be efficiently expressed in the two cell lines and greatly inhibit the cell growth. Its efficiency didn't depend on the intrinsic p53 genetic status. After irradiation, its function of inducing G 1 arrest and apoptosis on GLC-82 cell line was much stronger than the A549 cell line. In both the A549 and GLC-82 cell lines, the combination of Ad-p53 plus radiation resulted in more apoptosis than the others. There was no significant difference between two groups. Conclusions: Ad-p53 can depress the tumor growth and enhance the radiosensitivity of human lung adenocarcinoma cells. And this effect is independent of endogenous p53 status. (authors)

Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

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Yubing Xie

2011-11-01

Full Text Available Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enable better understanding of ES cell-breast cancer cell interactions, help elucidate tumorigenesis, and lead to the restriction of breast cancer metastasis. In this article, we will present the characteristics of breast cancer cells and ES cells as well as their microenvironments, importance of embryonic microenvironments in inhibiting tumorigenesis, convergence of tumorigenic and embryonic signaling pathways, and state of the art in bioengineering embryonic microenvironments for breast cancer research. Additionally, the potential application of bioengineered embryonic microenvironments for the prevention and treatment of invasive breast cancer will be discussed.

Clear Cell Adenocarcinoma Arising from Abdominal Wall Endometriosis

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Thouraya Achach

2008-01-01

Full Text Available Endometriosis is a frequent benign disorder. Malignancy arising in extraovarian endometriosis is a rare event. A 49-year-old woman is presented with a large painful abdominal wall mass. She underwent a myomectomy, 20 years before, for uterus leiomyoma. Computed tomography suggested that this was a desmoid tumor and she underwent surgery. Histological examination showed a clear cell adenocarcinoma associated with endometriosis foci. Pelvic ultrasound, computed tomography, and endometrial curettage did not show any malignancy or endometriosis in the uterus and ovaries. Adjuvant chemotherapy was recommended, but the patient was lost to follow up. Six months later, she returned with a recurrence of the abdominal wall mass. She was given chemotherapy and then she was reoperated.

Iron overload of human colon adenocarcinoma cells studied by synchrotron-based X-ray techniques

NARCIS (Netherlands)

Mihucz, Victor G.; Meirer, Florian; Polgári, Zsófia; Réti, Andrea; Pepponi, Giancarlo; Ingerle, Dieter; Szoboszlai, Norbert; Streli, Christina

2016-01-01

Fast- and slow-proliferating human adenocarcinoma colorectal cells, HT-29 and HCA-7, respectively, overloaded with transferrin (Tf), Fe(III) citrate, Fe(III) chloride and Fe(II) sulfate were studied by synchrotron radiation total-reflection X-ray spectrometry (TXRF), TXRF-X-ray absorption near edge

Sulforaphane?induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC?05

OpenAIRE

Zhou, Lan; Yao, Qian; Li, Yan; Huang, Yun?chao; Jiang, Hua; Wang, Chuan?qiong; Fan, Lei

2016-01-01

Background Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non?smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane?induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL?05) to explore the value of s...

Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in breast cancer.

Science.gov (United States)

Basudhar, Debashree; Cheng, Robert C; Bharadwaj, Gaurav; Ridnour, Lisa A; Wink, David A; Miranda, Katrina M

2015-06-01

Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

CEA-producing urothelial cell carcinoma with metastasis presenting as a rectal adenocarcinoma

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Ming-Hsin Yang

2012-11-01

Full Text Available This is a case study of a 61-year-old male who presented with difficult defecation for 1 month. A circumferential submucosal rectal tumor was noted on a digital rectal examination and colonoscopy. Laboratory examination revealed high serum levels of carcinoembryonic antigen (CEA; 43.75 ng/mL and carbohydrate antigen 19-9 (CA19-9; 11,790 U/mL. In addition, tumor biopsies revealed a poorly differentiated adenocarcinoma of the rectum with intact mucosa. The patient had history of advanced stage-T2 urothelial cell carcinoma of bladder, which had been downstaged to T0 by neoadjuvant chemotherapy followed by radical cystectomy 1 year prior. After investigating the initial bladder tumor specimens, a small portion of the tumor with high CEA expression comparable to the submucosal rectal tumor was found. The size of the tumor was reduced and the levels of the tumor markers decreased after administering FOLFIRI chemotherapy targeted at the adenocarcinoma. Although neoadjuvant chemotherapy may have a selective pressure to eliminate most urothelial cell carcinoma, physicians should be aware that it can lead to rectal metastasis via CEA-producing components.

ESOPHAGEAL CARCINOMA: IS SQUAMOUS CELL CARCINOMA DIFFERENT DISEASE COMPARED TO ADENOCARCINOMA? A transversal study in a quaternary high volume hospital in Brazil

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Francisco TUSTUMI

Full Text Available ABSTRACT Background Esophageal cancer is one of the leading causes of mortality among the neoplasms that affect the gastrointestinal tract. There are several factors that contribute for development of an epidemiological esophageal cancer profile in a population. Objective This study aims to describe both clinically and epidemiologically the population of patients with diagnosis of esophageal cancer treated in a quaternary attention institute for cancer from January, 2009 to December, 2011, in Sao Paulo, Brazil. Methods The charts of all patients diagnosed with esophageal cancer from January, 2009, to December, 2011, in a Sao Paulo (Brazil quaternary oncology institute were retrospectively reviewed. Results Squamous cell cancer made up to 80% of the cases of esophageal cancer. Average age at diagnosis was 60.66 years old for esophageal adenocarcinoma and 62 for squamous cell cancer, average time from the beginning of symptoms to the diagnosis was 3.52 months for esophageal adenocarcinoma and 4.2 months for squamous cell cancer. Average time for initiating treatment when esophageal cancer is diagnosed was 4 months for esophageal adenocarcinoma and 4.42 months for squamous cell cancer. There was a clear association between squamous cell cancer and head and neck cancers, as well as certain habits, such as smoking and alcoholism, while adenocarcinoma cancer showed more association with gastric cancer and gastroesophageal reflux disease. Tumoral bleeding and pneumonia were the main causes of death. No difference in survival rate was noted between the two groups. Conclusion Adenocarcinoma and squamous cell carcinoma are different diseases, but both are diagnosed in advanced stages in Brazil, compromising the patients' possibilities of cure.

Carboplatin treatment of antiestrogen-resistant breast cancer cells

DEFF Research Database (Denmark)

Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

2012-01-01

Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...

Metastasis of breast cancer rectum

International Nuclear Information System (INIS)

Suárez, L.; Santander, G.

2004-01-01

Introduction: Metastases to the breast are rare, corresponding approximately to 3% of breast cancers. Primary tumors that spread more commonly are own breast, often following them in melanomas, neuroendocrine, ovarian and lymphoma. Medical history: A 59-year consultation rectoragias repeated and thinning. It is studied and finally intervenes (low anterior resection) diagnosed with rectal cancer whose Histopathology revealed a poorly differentiated adenocarcinoma stage III. Concomitantly the patient has a left breast lump that was studied with mammography, which revealed a dense mass of larger diameter 4 cm in topografiada 3 hour left breast with well defined contours and ultrasonographic structure solid. MI lumpectomy is performed whose pathology reports a poorly differentiated adenocarcinoma with cytoarchitectural features matching the lesion of rectum. Hormone receptors were negative. The patient is treated as a rectal cancer with RT spread over QT (5FU i /c). Died 7 months after diagnosis. Discusion: In literature are reported only 3 cases of breast metastases secondary to rectal cancer; how unusual this presentation justify this report.In this event they occurred in patients with a previous diagnosis of rectal cancer and in the context of systemic lesion progression. In our case clinician early diagnosis of rectal and breast metastases was synchronous. The mammographic image consistent with those described for these cases in the literature.The development of metastases in breast tissue is associated with a poor prognosis as which correlates with the survival of the patient

Breast cancer cell lines: friend or foe?

International Nuclear Information System (INIS)

Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

2003-01-01

The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research

Squamous cell carcinoma of the breast : a case report

NARCIS (Netherlands)

Flikweert, Elvira R.; Hofstee, Mans; Liem, Mike S. L.

2008-01-01

Background: Squamous cells are normally not found inside the breast, so a primary squamous cell carcinoma of the breast is an exceptional phenomenon. There is a possible explanation for these findings. Case presentation: A 72-year-old woman presented with a breast abnormality suspected for breast

Black cohosh inhibits 17β-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

Science.gov (United States)

Park, So Yun; Kim, Hee Ja; Lee, Sa Ra; Choi, Youn-Hee; Jeong, Kyungah; Chung, Hyewon

2016-10-01

This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 μM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17β-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 μM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

Internalization and Recycling of the HER2 Receptor on Human Breast Adenocarcinoma Cells Treated with Targeted Phototoxic Protein DARPinminiSOG

Science.gov (United States)

Shilova, O. N.; Proshkina, G. M.; Lebedenko, E. N.; Deyev, S. M.

2015-01-01

Design and evaluation of new high-affinity protein compounds that can selectively and efficiently destroy human cancer cells are a priority research area in biomedicine. In this study we report on the ability of the recombinant phototoxic protein DARPin-miniSOG to interact with breast adenacarcinoma human cells overexpressing the extracellular domain of human epidermal growth factor receptor 2 (HER2). It was found that the targeted phototoxin DARPin-miniSOG specifically binds to the HER2 with following internalization and slow recycling back to the cell membrane. An insight into the role of DARPin-miniSOG in HER2 internalization could contribute to the treatment of HER2-positive cancer using this phototoxic protein. PMID:26483969

Adenocarcinoma of urinary bladder: A report of two patients

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Nitu Kumari

2015-01-01

Full Text Available Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER, gross cystic disease fluid protein 15 (GCDFP15, 34bE12, and prostate specific antigen (PSA provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

Adenocarcinoma of urinary bladder: A report of two patients.

Science.gov (United States)

Kumari, Nitu; Vasudeva, Pawan; Kumar, Anup; Agrawal, Usha

2015-01-01

Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.

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Denise K Reaves

Full Text Available The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior.

Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

Science.gov (United States)

Degnim, Amy C; Hoskin, Tanya L; Arshad, Muhammad; Frost, Marlene H; Winham, Stacey J; Brahmbhatt, Rushin A; Pena, Alvaro; Carter, Jodi M; Stallings-Mann, Melody L; Murphy, Linda M; Miller, Erin E; Denison, Lori A; Vachon, Celine M; Knutson, Keith L; Radisky, Derek C; Visscher, Daniel W

2017-07-15

Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD). Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm 2 for CD4 + T cells, CD8 + T cells, CD20 + B cells, and CD68 + macrophages and quantification of positive pixel measure for CD11c (dendritic cells). Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8 + T cells, CD11c + dendritic cells, CD20 + B cells, and CD68 + macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20 + cell density ( P = 0.04). Nearly 42% of BBD cases had no CD20 + B cells in evaluated lobules compared with 28% of BBD controls ( P = 0.02). The absence of CD20 + cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk. Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

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Erika Suzuki

Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

Effect of radiation on the expression of tumor-associated antigens of human lung adenocarcinoma cells

International Nuclear Information System (INIS)

Hareyama, Masato

1988-01-01

We studied the effects of irradiation on the expression of a tumor-associated antigen (YH206 antigen) of cultured human lung adenocarcinoma A549 cells by using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. YH206 antigen is preferentially expressed on adenocarcinoma cells. Irradiation of A549 cells remarkably increased the expression of YH206 antigen on the cell surface and the level of the antigen in the culture supernatant as well as in the cell lysate, whereas it significantly affected the expression of HLA (MHC-class I) antigen on the same cells. The expression of HLA antigen on the cell was also increased after treatment of the cells with interferon-γ. In an additional experiment, cells were stained simultaneously for surface antigens (fluorescein coupled antibodies) and for DNA content (propidium iodide), and then dual parameter measurements were performed by flow cytometry to analyse the relationship between antigen levels and the cell cycle. YH206 antigen and HLA antigen increased more in the S and G 2 /M phases of the cell cycle than in G 0 /G 1 . The expression of YH206 antigen was enhanced in the S and G 2 /M phases by irradiation, whereas the expression of HLA antigen was enhanced in each phase of the cell cycle with irradiation or IFN. These results suggest that irradiation plays a key role in the change of the expression of certain tumor-associated antigens. (author)

Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing

DEFF Research Database (Denmark)

Madsen, Caroline B; Lavrsen, Kirstine; Steentoft, Catharina

2013-01-01

are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing...... only the shortest possible mucin-like glycans (Tn and STn). Glyco-engineering was performed by zinc finger nuclease (ZFN) knockout (KO) of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast...

Synchronous primary adenocarcinoma and adenosquamous carcinoma of the esophagus

International Nuclear Information System (INIS)

Cirillo, L.C.; Franco, R.; Gatta, G.; Rosa, G. de; Mainenti, P.P.; Imbriaco, M.; Salvatore, M.

2001-01-01

Multiple malignant esophageal tumors of the same cell type are described. In the esophageal mucosa, widespread carcinomatous transformation may be observed and multicentric invasive squamous cell carcinomas may develop. The concomitance of two independent esophageal malignant neoplasms of different epithelial histogenesis is uncommon. Synchronous adenocarcinoma and squamous cell carcinoma of the esophagus is reported. Adenosquamous carcinoma of the esophagus is a rare tumor. Adenocarcinoma of the esophagus represents 10% of esophageal cancer. We report a case of a synchronous primary invasive adenosquamous carcinoma and adenocarcinoma of the esophagus. Both tumors were demonstrated radiographically. The peculiarity of this neoplastic association and the importance of complete radiographic esophageal evaluation in patients with one obvious obstructing tumor of the esophagus are emphasized. (orig.)

Myeloid-derived suppressor cells in breast cancer.

Science.gov (United States)

Markowitz, Joseph; Wesolowski, Robert; Papenfuss, Tracey; Brooks, Taylor R; Carson, William E

2013-07-01

Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells defined by their suppressive actions on immune cells such as T cells, dendritic cells, and natural killer cells. MDSCs typically are positive for the markers CD33 and CD11b but express low levels of HLADR in humans. In mice, MDSCs are typically positive for both CD11b and Gr1. These cells exert their suppressive activity on the immune system via the production of reactive oxygen species, arginase, and cytokines. These factors subsequently inhibit the activity of multiple protein targets such as the T cell receptor, STAT1, and indoleamine-pyrrole 2,3-dioxygenase. The numbers of MDSCs tend to increase with cancer burden while inhibiting MDSCs improves disease outcome in murine models. MDSCs also inhibit immune cancer therapeutics. In light of the poor prognosis of metastatic breast cancer in women and the correlation of increasing levels of MDSCs with increasing disease burden, the purposes of this review are to (1) discuss why MDSCs may be important in breast cancer, (2) describe model systems used to study MDSCs in vitro and in vivo, (3) discuss mechanisms involved in MDSC induction/function in breast cancer, and (4) present pre-clinical and clinical studies that explore modulation of the MDSC-immune system interaction in breast cancer. MDSCs inhibit the host immune response in breast cancer patients and diminishing MDSC actions may improve therapeutic outcomes.

Rhein Induces Apoptosis in Human Breast Cancer Cells

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Ching-Yao Chang

2012-01-01

Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

The role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma cell line PC-9 induced by icotinib.

Science.gov (United States)

Zhang, Yuping; Meng, Xia; Shi, Hongyang; Li, Wei; Ming, Zongjuan; Zhong, Yujie; Deng, Wenjing; Zhang, Qiuhong; Fan, Na; Niu, Zequn; Chen, Guo'an; Yang, Shuanying

2016-01-01

The aim of this study is to estimate the role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma induced by icotinib. EGFR mutation was detected in lung adenocarcinoma cell line PC-9 by ARMS assay; The inhibitory rates of cell proliferation of PC-9 cells which were exposed to different concentrations of icotinib (0~100 μMol/L) for different time (24~72 h) respectively were evaluated by MTT assay; Apoptosis of PC-9 cells exposed to different concentrations of icotinib (0, 0.1, 1 and 10 μMol/L) for 48 h were evaluated by TUNEL assay; JAK2, STAT3, Bcl-2, Bax mRNA expressions were evaluated by Real-time PCR assay; The protein levels of P-STAT3 and IL-6 were evaluated by Western-blot assay. Human lung adenocarcinoma cell line PC-9 had an exon 19 deletion mutation in EGFR gene; Followed by treatment of icotinib, the proliferation of PC-9 cells were all inhibited significantly, especially in 48 and 72 h (Picotinib. The most likely mechanism is icotinib inhibited the gene expression levels of JAK2, STAT3 and Bcl-2, so with the P-STAT3 and IL-6 protein levels, and mediated gene Bax overexpression.

Interfacing polymeric scaffolds with primary pancreatic ductal adenocarcinoma cells to develop 3D cancer models

NARCIS (Netherlands)

Ricci, C.; Mota, C.M.; Moscato, S.; D' Alessandro, D.; Ugel, S.; Sartoris, S.; Bronte, V.; Boggi, U.; Campani, D.; Funel, N.; Moroni, Lorenzo; Danti, S.

2014-01-01

We analyzed the interactions between human primary cells from pancreatic ductal adenocarcinoma (PDAC) and polymeric scaffolds to develop 3D cancer models useful for mimicking the biology of this tumor. Three scaffold types based on two biocompatible polymeric formulations, such as poly(vinyl

Infiltration of peritumoural but tumour-free parenchyma with IgG4-positive plasma cells in hilar cholangiocarcinoma and pancreatic adenocarcinoma.

Science.gov (United States)

Resheq, Yazid J; Quaas, Alexander; von Renteln, Daniel; Schramm, Christoph; Lohse, Ansgar W; Lüth, Stefan

2013-10-01

Recently, new guidelines for diagnosing IgG4-associated cholangitis have been published devaluing the diagnostic significance of IgG4-positive plasma cells and steroid trials. We sought to evaluate the utility of IgG4-positive plasma cells in discriminating IgG4-associated cholangitis from hilar cholangiocarcinoma and autoimmune pancreatitis from pancreatic adenocarcinoma under conditions when malignancy is likely to be missed. Resection specimens obtained from patients with hilar cholangiocarcinoma, pancreatic adenocarcinoma or hepatocellular carcinoma were re-evaluated for IgG4-positivity. Histological analysis focussed on peritumoural but tumour-free sections. Perioperative biochemical and clinical data were reviewed. Nineteen patients with hilar cholangiocarcinoma and 29 patients with pancreatic adenocarcinoma were eligible for histological re-evaluation. Six of 19 (32%) patients with hilar cholangiocarcinoma and 5 of 29 (17%) patients with pancreatic adenocarcinoma were IgG4-positive (≥20 IgG4-positive plasma cells per high power field). Patients with IgG4-positive hilar cholangiocarcinoma showed significantly higher levels of serum total bilirubin (3.6mg/dl vs. 1.8mg/dl; Philar cholangiocarcinoma. IgG4-positive plasma cells are of limited utility especially in distinguishing hilar cholangiocarcinoma from IgG4-associated cholangitis even when combined with clinical parameters and may be misleading under conditions when malignancy is missed. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

International Nuclear Information System (INIS)

Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

2006-01-01

Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

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Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

2011-01-01

Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

Molecular biology of breast cancer stem cells: potential clinical applications.

Science.gov (United States)

Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

2010-10-01

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

Expression of p53 protein in Barrett’s adenocarcinoma and adenocarcinoma of the gastric cardia and antrum

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Jovanović Ivan

2005-01-01

Full Text Available Background/Aim. Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumor site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum. The aim of our study was to analyze the correlation between the selected clinico-pthological parameters, and p53 protein overexpression in regards to the particular tumor location. Methods. The material comprised 66 surgical specimens; 10 were Barrett’s carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction - EGJ, and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase - antialkaline phosphatase (APAAP method. The cases were considered positive for p53 if at least 5% of the tumor cells expressed this protein by immunostaining. Results. There was no significant difference observed between the studied groups in regards to age, sex, Lauren’s classification and tumor differentiation. There was, however, a significant difference observed in the depth of tumor invasion between Barrrett’s adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett’s adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10 of Barrett’s adenocarcinomas, 72% (18/25 of adenocarcinoma of the cardia and 65% (20/31 of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren of tumor, depth of invasion, lymph node involvement, or tumor differentiation were observed in any of the analyzed groups of tumors. Patients with more advanced Barrett�

Endothelial induced EMT in breast epithelial cells with stem cell properties

DEFF Research Database (Denmark)

Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla

2011-01-01

endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression...... of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D......492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close...

Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

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Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

2017-02-01

Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Histologic transformation from adenocarcinoma to both small cell lung cancer and squamous cell carcinoma after treatment with gefitinib: A case report.

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Yao, Yufeng; Zhu, Zhouyu; Wu, Yimin; Chai, Ying

2018-05-01

In the past decade, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment had been an important therapy for treating advanced EGFR-mutated lung cancer patients. However, a large number of these patients with EGFR-TKIs treatment always acquired resistance to these drugs in one year. The histologic transformation is an important resistance mechanism. Here we reported a 41-year-old man with EGFR-mutated lung adenocarcinoma and he showed histologic transformation to both small-cell lung cancer (SCLC) and squamous cell carcinoma (SCC) after treatment of gefitinib. A case of EGFR-mutated lung cancer. Medical thoracoscopy examination was performed and the patient was diagnosed as a EGFR-mutated lung adenocarcinoma. Then gefitinib was administered orally at a dose of 250 mg daily. The patient received treatment with chemotherapy (etoposide 0.1 g day 2-5 +  cis-platinum 30 mg day 2-4) after acquiring resistance to gefitinib. The patient died in April 2017 that survived for 32 months from lung cancer was found for the first time. To the best of our knowledge, it is the first case of EGFR-mutated lung adenocarcinoma transforming to both SCLC and SCC which was treated with and responded to gefitinib.

Mast cells and eosinophils in invasive breast carcinoma

International Nuclear Information System (INIS)

Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

2007-01-01

Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

OpenAIRE

Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

2009-01-01

The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells

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Charpentier, Monica; Martin, Stuart

2013-01-01

Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of α-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis

Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells

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Charpentier, Monica [Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-20, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States); Martin, Stuart, E-mail: ssmartin@som.umaryland.edu [Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States); Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States)

2013-11-14

Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of α-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis.

Generation of Breast Cancer Stem Cells by the EMT

Science.gov (United States)

2009-10-01

shift in the type of human breast cancer cells. We began to use experimentally immortalized HMLE cells that were then transformed through...Generation of Breast Cancer Stem Cells by the EMT PRINCIPAL INVESTIGATOR: Robert A. Weinberg, Ph.D. CONTRACTING...Generation of Breast Cancer Stem Cells by the EMT 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0464 5c. PROGRAM ELEMENT NUMBER 6

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

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Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-04-19

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

International Nuclear Information System (INIS)

Fleming, Jodie M; Ginsburg, Erika; Oliver, Shannon D; Goldsmith, Paul; Vonderhaar, Barbara K

2012-01-01

Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca 2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H 2 O 2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast

Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

Directory of Open Access Journals (Sweden)

Fleming Jodie M

2012-06-01

Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its

Endothelial Induced EMT in Breast Epithelial Cells with Stem Cell Properties

OpenAIRE

Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla; Fridriksdottir, Agla J. R.; Ringnér, Markus; Villadsen, Rene; Borg, Ake; Agnarsson, Bjarni A.; Petersen, Ole William; Magnusson, Magnus K.; Gudjonsson, Thorarinn

2011-01-01

Epithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell proper...

Distinct Histopathologic and Molecular Alterations in Inflammatory Bowel Disease-Associated Intestinal Adenocarcinoma: c-MYC Amplification is Common and Associated with Mucinous/Signet Ring Cell Differentiation.

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Hartman, Douglas J; Binion, David G; Regueiro, Miguel D; Miller, Caitlyn; Herbst, Cameron; Pai, Reetesh K

2018-05-17

Chronic idiopathic inflammatory bowel disease (IBD) is a significant risk factor for the development of intestinal adenocarcinoma. The underlying molecular alterations in IBD-associated intestinal adenocarcinoma remain largely unknown. We compared the clinicopathologic and molecular features of 35 patients with 47 IBD-associated intestinal adenocarcinomas with a consecutive series of 451 patients with sporadic colorectal carcinoma identified at our institution and published data on sporadic colorectal carcinoma. c-MYC amplification was the most frequent molecular alteration identified in 33% of IBD-associated intestinal adenocarcinoma that is a significantly higher frequency than in sporadic colorectal carcinoma (8%) (P = 0.0001). Compared to sporadic colorectal carcinoma, IBD-associated intestinal adenocarcinomas more frequently demonstrated mucinous differentiation (60% vs 25%, P < 0.001) and signet ring cell differentiation (28% vs 4%, P < 0.001). Mucinous and signet ring cell differentiation were significantly associated with the presence of c-MYC amplification (both with P < 0.05). HER2 positivity (11%), KRAS exon 2 or 3 mutation (10%), and IDH1 mutation (7%) were less commonly observed in IBD-associated intestinal adenocarcinoma. There was an association between poor survival and HER2 status with 3 of 4 patients having HER2-positive adenocarcinoma dead of disease at last clinical follow-up; however, no statistically significant survival effect was identified for any of the molecular alterations identified. We demonstrate that IBD-associated intestinal adenocarcinomas have a high frequency of c-MYC amplification that is associated with mucinous and signet ring cell differentiation. Many of the identified molecular alterations have potential therapeutic relevance, including HER2 amplification, IDH1 mutation, and low frequency KRAS mutation.

Breast Cancer Mimic: Cutaneous B-Cell Lymphoma Presenting as an Isolated Breast Mass

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Margaret Taghavi

2014-10-01

Full Text Available Background: Primary cutaneous B-cell lymphoma typically localizes to the skin, and dissemination to internal organs is rare. Lymphomatous involvement of the breasts is also rare. We describe the clinical and radiological findings of an unusual case of primary cutaneous B-cell lymphoma presenting as an isolated breast mass without associated skin changes. Case Presentation: The patient was a 55-year-old Caucasian female who initially presented with cutaneous B-cell lymphoma around her eyes and forehead with recurrence involving the skin between her breasts. Three years after terminating treatment due to a lack of symptoms, she presented for an annual screening mammogram that found a new mass in her upper inner right breast without imaging signs of cutaneous extension. On physical examination, there were no corresponding skin findings. Due to the suspicious imaging features of the mass that caused concern for primary breast malignancy, she underwent a core biopsy which revealed cutaneous B-cell lymphoma. Conclusion: When evaluating patients with a systemic disease who present with findings atypical for that process, it is important to still consider the systemic disease as a potential etiology, particularly with lymphoma given its reputation as a great mimicker.

Aptamer based electrochemical sensor for detection of human lung adenocarcinoma A549 cells

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Sharma, Rachna; Varun Agrawal, Ved; Sharma, Pradeep; Varshney, R.; Sinha, R. K.; Malhotra, B. D.

2012-04-01

We report results of the studies relating to development of an aptamer-based electrochemical biosensor for detection of human lung adenocarcinoma A549 cells. The aminated 85-mer DNA aptamer probe specific for the A549 cells has been covalently immobilized onto silane self assembled monolayer (SAM) onto ITO surface using glutaraldehyde as the crosslinker. The results of cyclic voltammetry and differential pulse voltammetry studies reveal that the aptamer functionalized bioelectrode can specifically detect lung cancer cells in the concentration range of 103 to 107 cells/ml with detection limit of 103 cells/ml within 60 s. The specificity studies of the bioelectrode have been carried out with control KB cells. No significant change in response is observed for control KB cells as compared to that of the A549 target cells.

Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström’s macroglobulinaemia

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Radojković Milica

2011-01-01

Full Text Available Introduction. Waldenström’s macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström’s macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström’s macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. Case Outline. A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström’s macroglobulinaemia. Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström’s macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. Conclusion. The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenström’s macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors.

Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

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Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

2015-01-01

Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

Mucinous adenocarcinoma of posterior urethra. Report of a case.

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Yvgenia, Rosenblat; Ben Meir, David; Sibi, Joseph; Koren, Rumelia

2005-01-01

Primary carcinoma of the male urethra accounts for less than 1% of malignancies in males. Mucinous adenocarcinoma of the urethra is extremely rare, and its biologic behavior is not well known. We report a case of mucinous adenocarcinoma showing the histologic features of colloid adenocarcinoma that appears to have evolved either by neoplastic degeneration of goblet cells found in the urethral epithelium or by malignant degeneration of persistent glandular elements of uretheritis cystica and glandularis.

Serum deprivation induces glucose response and intercellular coupling in human pancreatic adenocarcinoma PANC-1 cells.

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Hiram-Bab, Sahar; Shapira, Yuval; Gershengorn, Marvin C; Oron, Yoram

2012-03-01

This study aimed to investigate whether the previously described differentiating islet-like aggregates of human pancreatic adenocarcinoma cells (PANC-1) develop glucose response and exhibit intercellular communication. Fura 2-loaded PANC-1 cells in serum-free medium were assayed for changes in cytosolic free calcium ([Ca]i) induced by depolarization, tolbutamide inhibition of K(ATP) channels, or glucose. Dye transfer, assayed by confocal microscopy or by FACS, was used to detect intercellular communication. Changes in messenger RNA (mRNA) expression of genes of interest were assessed by quantitative real-time polymerase chain reaction. Proliferation was assayed by the MTT method. Serum-deprived PANC-1 cell aggregates developed [Ca]i response to KCl, tolbutamide, or glucose. These responses were accompanied by 5-fold increase in glucokinase mRNA level and, to a lesser extent, of mRNAs for K(ATP) and L-type calcium channels, as well as increase in mRNA levels of glucagon and somatostatin. Trypsin, a proteinase-activated receptor 2 agonist previously shown to enhance aggregation, modestly improved [Ca]i response to glucose. Glucose-induced coordinated [Ca]i oscillations and dye transfer demonstrated the emergence of intercellular communication. These findings suggest that PANC-1 cells, a pancreatic adenocarcinoma cell line, can be induced to express a differentiated phenotype in which cells exhibit response to glucose and form a functional syncytium similar to those observed in pancreatic islets.

Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Tsutani, Yasuhiro; Miyata, Yoshihiro; Misumi, Keizo; Ikeda, Takuhiro; Mimura, Takeshi; Hihara, Jun; Okada, Morihito

2011-01-01

This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n=132) or squamous cell carcinoma (n=44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P 6.95 (P=0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P<0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P<0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P=0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P=0.001). Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung. (author)

Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis.

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Xu, Lu-Lu; Guo, Shu-Liang; Ma, Su-Ren; Luo, Yong-Ai

2012-01-01

Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research groups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments.

Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component.

Directory of Open Access Journals (Sweden)

Qing Wei

Full Text Available We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.A slight male predominance was detected in these patients (59.0%. Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54 cases with KRAS mutations in 16.7% (9/54 cases and Nras mutations in 5.4%(3/54 cases. BRAF V600E mutation was detected in 3.7% (2/54 cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9% cases were composed of ≥50% signet-ring cells; 22 (36.1% cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of

Effect of silencing of ATM expression by siRNA on radiosensitivity of human lung adenocarcinoma A549 cells

International Nuclear Information System (INIS)

Liu Xiaoqun; Qiao Tiankui

2014-01-01

Objective: To investigate the effect of silencing of ataxia-telangiectasia mutated (ATM) expression by plasmid-mediated RNA interference on the radiosensitivity of human lung adenocarcinoma A 549 cells. Methods: Eukaryotic expression plasmid containing ATM small interfering RNA (siRNA) (pSilencer2.1-ATM), as well as pSilencer2.1-nonspecific, was constructed.Lung adenocarcinoma A 549 cells were divided into positive group, negative group,and control group to be transfected with pSilencer2.1-ATM, pSilencer2.1-nonspecific, and no plasmid, respectively. The mRNA and protein expression of ATM was measured by RT-PCR and Western blot, respectively. The change in cell radiosensitivity was observed by colony-forming assay. Cell cycle and cell apoptosis were analyzed by flow cytometry. Results: The eukaryotic expression plasmid containing ATM siRNA was successfully constructed. The RT-PCR and Western blot demonstrated that the expression of ATM was down-regulated in the positive group. The sensitization enhancement ratios (D 0 ratios) for the positive group and negative group were 1.50 and 1.01, respectively. The flow cytometry revealed that the proportions of A 549 cells in G 1 and G 2 /M phases were significantly lower in the positive group than in the control group (51.27% vs 61.85%, P = 0.012; 6.34% vs 10.91%, P = 0.008) and that the apoptosis rate was significantly higher in the positive group than in the control group and negative group (49.31% vs 13.58%, P = 0.000; 49.31% vs 13.17%, P = 0.000). Conclusions: Silencing of ATM expression may increase the radiosensitivity of human lung adenocarcinoma A 549 cells, probably by affecting the cell cycle and promoting cell apoptosis. (authors)

Expression profiles of cancer stem cell markers: CD133, CD44, Musashi-1 and EpCAM in the cardiac mucosa-Barrett's esophagus-early esophageal adenocarcinoma-advanced esophageal adenocarcinoma sequence.

Science.gov (United States)

Mokrowiecka, Anna; Veits, Lothar; Falkeis, Christina; Musial, Jacek; Kordek, Radzislaw; Lochowski, Mariusz; Kozak, Jozef; Wierzchniewska-Lawska, Agnieszka; Vieth, Michael; Malecka-Panas, Ewa

2017-03-01

Barrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE - EAC sequence are not fully elucidated yet. We used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies. All markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS). Our results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa. Copyright © 2016 Elsevier GmbH. All rights reserved.

Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

Energy Technology Data Exchange (ETDEWEB)

Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

2012-03-15

A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

A regulatory network for human adenocarcinoma

African Journals Online (AJOL)

AJL

2012-03-13

Mar 13, 2012 ... Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer and its absolute incidence is increasing ... Lung carcinomas are usually classified as small-cell lung ..... such as embryonic development, reproduction, and. TYMS .... homeostatic processes including stem cell maintenance,.

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

Science.gov (United States)

Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

2014-11-11

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

Nerve Invasion by Epithelial Cells in Benign Breast Diseases

Directory of Open Access Journals (Sweden)

Yu-Jan Chan

2009-03-01

Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro

OpenAIRE

Feng, Xiuli; Zhang, Yan; Li, Tao; Li, Yu

2017-01-01

Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A54...

Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

Science.gov (United States)

2015-11-01

1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

Leptomeningeal carcinomatosis from urinary bladder adenocarcinoma: a clinicopathological case study.

Science.gov (United States)

Sugimori, Kaoru; Kobayashi, Katsuji; Hayashi, Masahiro; Sakai, Naoto; Sasaki, Motoko; Koshino, Yoshifumi

2005-03-01

We report a 73-year-old male patient with leptomeningeal metastasis from urinary bladder adenocarcinoma. He was presented with prominent hyperactive delirium during the course of the disease. Meningeal carcinomatosis was detected 5 days before his death, but the primary site of the malignant tumor could not be determined. Necropsy revealed leptomeningeal infiltration of many adenocarcinoma cells that covered the cerebrum. The leptomeninges of the right middle frontal gyrus, superior temporal gyrus, precentral gyrus and inferior parietal lobe were most severely affected by tumor cell infiltration. Cerebral edema was found to extensively cover the basal part of the temporal lobe. In the cerebrum, tumor cells were clustered in the perivascular spaces and had invaded localized areas of the frontal lobe. Vascular cell adhesion molecule (VCAM)-1 expression was detected in the small vessels of the cerebral upper cortical layers and of temporal subcortical u-fibers. Numerous astrocytes positive for cytokeratin AE1/AE3 were found in the frontal and temporal lobes. Meningeal carcinomatosis from urinary bladder adenocarcinoma is extremely rare and up-regulation of the adhesion molecules in the meningeal adenocarcinoma was confirmed.

Breast Cancer Resistance to Cyclophosphamide and Other Oxazaphosphorines.

Science.gov (United States)

1997-10-01

human breast adenocarcinoma MCF-7/0 cells. d-Limonene, a monoterpene abundantly present in citrus fruits and various other foods common to most diets...and ARE-B. e.g., catechol, inducers, Figure 12 and Table 3, vide supra. Given the foregoing, the expectation was that the monoterpenes would induce the...less effectively than ALDH-1 (data not shown). r I r I I (I) o 300 7 I~Cl) S20 E -- 0 1 O 25 cc 1 2 3 1 2 3 Monoterpene , log iM Monoterpene , log pM

Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast epithelial cells.

Science.gov (United States)

Hilmarsdottir, Bylgja; Briem, Eirikur; Halldorsson, Skarphedinn; Kricker, Jennifer; Ingthorsson, Sævar; Gustafsdottir, Sigrun; Mælandsmo, Gunhild M; Magnusson, Magnus K; Gudjonsson, Thorarinn

2017-05-11

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell-cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype.

Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

Energy Technology Data Exchange (ETDEWEB)

Li, Jie [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Yang, Xi-fei [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Ren, Xiao-hu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Meng, Xiao-jing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Huang, Hai-yan [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zhao, Qiong-hui [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen (China); Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Liu, Jian-jun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China)

2014-10-10

Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

International Nuclear Information System (INIS)

Li, Jie; Yang, Xi-fei; Ren, Xiao-hu; Meng, Xiao-jing; Huang, Hai-yan; Zhao, Qiong-hui; Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li; Liu, Jian-jun; Zou, Fei

2014-01-01

Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer

Serous papillary adenocarcinoma possibly related to the presence of primitive oocyte-like cells in the adult ovarian surface epithelium: a case report

Directory of Open Access Journals (Sweden)

Virant-Klun Irma

2011-08-01

Full Text Available Abstract Introduction The presence of oocytes in the ovarian surface epithelium has already been confirmed in the fetal ovaries. We report the presence of SSEA-4, SOX-2, VASA and ZP2-positive primitive oocyte-like cells in the adult ovarian surface epithelium of a patient with serous papillary adenocarcinoma. Case presentation Ovarian tissue was surgically retrieved from a 67-year old patient. Histological analysis revealed serous papillary adenocarcinoma. A proportion of ovarian cortex sections was deparaffinized and immunohistochemically stained for the expression of markers of pluripotency SSEA-4 and SOX-2 and oocyte-specific markers VASA and ZP2. The analysis confirmed the presence of round, SSEA-4, SOX-2, VASA and ZP2-positive primitive oocyte-like cells in the ovarian surface epithelium. These cells were possibly related to the necrotic malignant tissue. Conclusion Primitive oocyte-like cells present in the adult ovarian surface epithelium persisting probably from the fetal period of life or developed from putative stem cells are a pathological condition which is not observed in healthy adult ovaries, and might be related to serous papillary adenocarcinoma manifestation in the adult ovarian surface epithelium. This observation needs attention to be further investigated.

Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

Directory of Open Access Journals (Sweden)

José J. Gaforio

2011-10-01

Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

File list: Unc.Brs.10.AllAg.Breast_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Brs.10.AllAg.Breast_cells hg19 Unclassified Breast Breast cells SRX265449,SRX26...5450 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Brs.10.AllAg.Breast_cells.bed ...

NF-κB signaling is activated and confers resistance to apoptosis in three-dimensionally cultured EGFR-mutant lung adenocarcinoma cells

International Nuclear Information System (INIS)

Sakuma, Yuji; Yamazaki, Yukiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Matsukuma, Shoichi; Koizume, Shiro; Miyagi, Yohei

2012-01-01

Highlights: ► EGFR-mutant cells in 3D culture resist EGFR inhibition compared with suspended cells. ► Degradation of IκB and activation of NF-κB are observed in 3D-cultured cells. ► Inhibiting NF-κB enhances the efficacy of the EGFR inhibitor in 3D-cultured cells. -- Abstract: Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells in suspension undergo apoptosis to a greater extent than adherent cells in a monolayer when EGFR autophosphorylation is inhibited by EGFR tyrosine kinase inhibitors (TKIs). This suggests that cell adhesion to a culture dish may activate an anti-apoptotic signaling pathway other than the EGFR pathway. Since the microenvironment of cells cultured in a monolayer are substantially different to that of cells existing in three-dimension (3D) in vivo, we assessed whether two EGFR-mutant lung adenocarcinoma cell lines, HCC827 and H1975, were more resistant to EGFR TKI-induced apoptosis when cultured in a 3D extracellular matrix (ECM) as compared with in suspension. The ECM-adherent EGFR-mutant cells in 3D were significantly less sensitive to treatment with WZ4002, an EGFR TKI, than the suspended cells. Further, a marked degradation of IκBα, the inhibitor of nuclear factor (NF)-κB, was observed only in the 3D-cultured cells, leading to an increase in the activation of NF-κB. Moreover, the inhibition of NF-κB with pharmacological inhibitors enhanced EGFR TKI-induced apoptosis in 3D-cultured EGFR-mutant cells. These results suggest that inhibition of NF-κB signaling would render ECM-adherent EGFR-mutant lung adenocarcinoma cells in vivo more susceptible to EGFR TKI-induced cell death.

Adipocyte activation of cancer stem cell signaling in breast cancer

Institute of Scientific and Technical Information of China (English)

Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

2015-01-01

Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

Science.gov (United States)

Alén, Begoña O; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S; Beiras, Andrés; Casanueva, Felipe F; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P; Pazos, Yolanda

2016-02-02

Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.

File list: DNS.Brs.50.AllAg.Breast_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Brs.50.AllAg.Breast_cells hg19 DNase-seq Breast Breast cells SRX081373,SRX08137...4,SRX201197 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Brs.50.AllAg.Breast_cells.bed ...

File list: DNS.Brs.20.AllAg.Breast_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Brs.20.AllAg.Breast_cells hg19 DNase-seq Breast Breast cells SRX081373,SRX08137...4,SRX201197 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Brs.20.AllAg.Breast_cells.bed ...

File list: DNS.Brs.10.AllAg.Breast_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Brs.10.AllAg.Breast_cells hg19 DNase-seq Breast Breast cells SRX081374,SRX08137...3,SRX201197 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Brs.10.AllAg.Breast_cells.bed ...

File list: DNS.Brs.05.AllAg.Breast_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Brs.05.AllAg.Breast_cells hg19 DNase-seq Breast Breast cells SRX081373,SRX08137...4,SRX201197 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Brs.05.AllAg.Breast_cells.bed ...

Syncytin is involved in breast cancer-endothelial cell fusions

DEFF Research Database (Denmark)

Bjerregaard, Bolette; Holck, S.; Christensen, I.J.

2006-01-01

Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

Oestrogen receptor beta over expression in males with non-small cell lung cancer is associated with better survival

DEFF Research Database (Denmark)

Skov, Birgit Guldhammer; Sode, Birgitte M Fischer; Pappot, H.

2008-01-01

BACKGROUND: Adenocarcinoma of the lung is more frequent in females than in males and the association with smoking is less pronounced than for the other histological subtypes of lung cancer. Oestrogen induction of cell proliferation has been found in breast adenocarcinomas, and since oestrogen...... the results to gender and survival. METHODS: Paraffin embedded, histological material was collected from 104 patients (71 men and 33 women), operated in the period 1989-1992 for NSCLC (56 squamous cell carcinomas, 40 adenocarcinomas and 8 large cell carcinomas). ERalpha, ERbeta and progesterone were...... and progesterone expression for the prognosis. RESULTS: ERbeta positivity was demonstrated in 69% (72 of 104) of the tumours. There was no statistically significant correlation between ERbeta positivity and age, gender, stage, or histology. After adjusting for gender, age, stage at diagnosis and histology...

Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells.

Science.gov (United States)

Liu, Jiaying; Yang, Longqiu; Guo, Xia; Jin, Guangli; Wang, Qimin; Lv, Dongdong; Liu, Junli; Chen, Qiu; Song, Qiong; Li, Baolin

2018-05-03

Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.

Promoting effects of adipose-derived stem cells on breast cancer cells are reversed by radiation therapy.

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Baaße, Annemarie; Juerß, Dajana; Reape, Elaine; Manda, Katrin; Hildebrandt, Guido

2018-04-01

Partial breast irradiation of early breast cancer patients after lumpectomy and the use of endogenous adipose tissue (AT) for breast reconstruction are promising applications to reduce the side effects of breast cancer therapy. This study tries to investigate the possible risks associated with these therapeutic approaches. It also examines the influence of adipose derived stem cells (ADSCs) as part of the breast cancer microenvironment, and endogenous AT on breast cancer cells following radiation therapy. ADSCs, isolated from human reduction mammoplasties of healthy female donors, exhibited multilineage capacity and specific surface markers. The promoting effects of ADSCs on the growth and survival fraction of breast cancer cells were reversed by treatment with high (8 Gy) or medium (2 Gy) radiation doses. In addition, a suppressing influence on breast cancer growth could be detected by co-culturing with irradiated ADSCs (8 Gy). Furthermore the clonogenic survival of unirradiated tumor cells was reduced by medium of irradiated ADSCs. In conclusion, radiation therapy changed the interactions of ADSCs and breast cancer cells. On the basis of our work, the importance of further studies to exclude potential risks of ADSCs in regenerative applications and radiotherapy has been emphasized.

The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants.

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Orciani, Monia; Lazzarini, Raffaella; Scartozzi, Mario; Bolletta, Elisa; Mattioli-Belmonte, Monica; Scalise, Alessandro; Di Benedetto, Giovanni; Di Primio, Roberto

2013-12-01

Breast implants are widely used and at times might cause inflammation as a foreign body, followed by fibrous capsule formation around the implant. In cancer, the inflamed stroma is essential for preservation of the tumor. Mesenchymal stem cells can be recruited to sites of inflammation, and their role in cancer development is debated. The authors assessed the effects of inflammation caused by breast implants' effects on tumor. Mesenchymal stem cells were isolated from the fibrous capsules of women who underwent a second operation after 1 year (presenting inflammation) or after 20 years (not presenting inflammation) since initial surgery. After characterization, cells were co-cultured with MCF7, a breast cancer cell line. The expression of genes involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition was investigated, followed by Western blot analyses. After co-culture with mesenchymal stem cells from the inflamed capsule, MCF7 induced a dose- and time-dependent increase in proliferation. Polymerase chain reaction analyses revealed a dysregulation of genes involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition. The subsequent evaluation by Western blot did not confirm these results, showing only a modest decrease in the expression of E-cadherin after co-culture with mesenchymal stem cells (both derived from inflamed or control capsules). These data indicate that inflammation caused by breast implants partially affects proliferation of MCF7 but does not influence key mechanisms of tumor development.

Anandamide inhibits adhesion and migration of breast cancer cells

International Nuclear Information System (INIS)

Grimaldi, Claudia; Pisanti, Simona; Laezza, Chiara; Malfitano, Anna Maria; Santoro, Antonietta; Vitale, Mario; Caruso, Maria Gabriella; Notarnicola, Maria; Iacuzzo, Irma; Portella, Giuseppe; Di Marzo, Vincenzo; Bifulco, Maurizio

2006-01-01

The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB 1 receptors could induce a non-invasive phenotype in breast mtastatic cells. In a model of metastatic spreading in vivo, the metabolically stable anandamide analogue, 2-methyl-2'-F-anandamide (Met-F-AEA), significantly reduced the number and dimension of metastatic nodes, this effect being antagonized by the selective CB 1 antagonist SR141716A. In MDA-MB-231 cells, a highly invasive human breast cancer cell line, and in TSA-E1 cells, a murine breast cancer cell line, Met-F-AEA inhibited adhesion and migration on type IV collagen in vitro without modifying integrin expression: both these effects were antagonized by SR141716A. In order to understand the molecular mechanism involved in these processes, we analyzed the phosphorylation of FAK and Src, two tyrosine kinases involved in migration and adhesion. In Met-F-AEA-treated cells, we observed a decreased tyrosine phosphorylation of both FAK and Src, this effect being attenuated by SR141716A. We propose that CB 1 receptor agonists inhibit tumor cell invasion and metastasis by modulating FAK phosphorylation, and that CB 1 receptor activation might represent a novel therapeutic strategy to slow down the growth of breast carcinoma and to inhibit its metastatic diffusion in vivo

[Right Hemi-Colectomy for a Metastatic Transverse Colon Tumor from Breast Cancer Following Bilateral Breast Cancer Resection - A Case Report].

Science.gov (United States)

Okamura, Shu; Yanagisawa, Tetsu; Ohishi, Kazuhito; Murata, Kohei; Nushijima, Yoichiro; Hamano, Rie; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

2016-11-01

We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery. Colonoscopy revealed stenosis of the same lesion with an edematous mucosa and sclerosis. Using immunohistochemistry, a biopsy specimen from the lesion tested positive for CK AE1+AE3, and negative for CD20(-)and CD3 (-). As a result, the tumor was diagnosed as a poorly differentiated adenocarcinoma. We performed right hemicolectomy to avoid her intestinal obstruction. Tumor cells were mainly present at the subserosa, according to HEstaining. Using immunostaining, the cells were tested for the following markers: CDX2(-), GCDFP15(weakly positive), CK7(strongly positive), CD20(partially positive), E R(+), PgR(-), and HER2(1+), characterizing the tumor as metastasis of breast cancer. Although gastro-intestinal metastasis from breast cancer is rare, and colon metastasis is even rarer, it might be necessary to rule out the possibility of a metastatic colon tumor from breast cancer when treating patients with a colon tumor who have undergone surgery for breast cancer.

Role of nuclear receptors in breast cancer stem cells

Institute of Scientific and Technical Information of China (English)

Alessio; Papi; Marina; Orlandi

2016-01-01

The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells,capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells(CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs(BCSCs) are likely to sustain the growth of the primary tumour mass, as wellas to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.

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McMurtry, Vanity; Saavedra, Joseph E; Nieves-Alicea, René; Simeone, Ann-Marie; Keefer, Larry K; Tari, Ana M

2011-04-01

Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.

The thioredoxin system in breast cancer cell invasion and migration

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Maneet Bhatia

2016-08-01

Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

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Zheng, Jin [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Qiang [Department of Hematology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jiandong [Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Ren, Qinyou [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Cao, Wei [Department of Interventional Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jingyue; Yu, Zhaocai [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yu, Fang [Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Xi' an, Shaanxi (China); Wu, Yanlan [Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Shi, Hengjun [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Wenchao [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China)

2012-04-27

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

International Nuclear Information System (INIS)

Zheng, Jin; Liu, Qiang; Yang, Jiandong; Ren, Qinyou; Cao, Wei; Yang, Jingyue; Yu, Zhaocai; Yu, Fang; Wu, Yanlan; Shi, Hengjun; Liu, Wenchao

2012-01-01

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells

MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer

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Zantek, Nicole Dodge; Walker-Daniels, Jennifer; Stewart, Jane; Hansen, Rhonda K.; Robinson, Daniel; Miao, Hui; Wang, Bingcheng; Kung, Hsing-Jien; Bissell, Mina J.; Kinch, Michael S.

2001-08-22

There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer. NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in threedimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.

Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

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Priscilla Ludovico da Silva

2015-12-01

Full Text Available The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma.

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Bernardi, Stella; Zennaro, Cristina; Palmisano, Silvia; Velkoska, Elena; Sabato, Nicoletta; Toffoli, Barbara; Giacomel, Greta; Buri, Luigi; Zanconati, Fabrizio; Bellini, Giuseppe; Burrell, Louise M; De Manzini, Nicolò; Fabris, Bruno

2012-03-01

A new arm of the renin-angiotensin system (RAS) has been recently characterized; this includes angiotensin converting enzyme (ACE)2 and angiotensin (Ang)1-7, a heptapeptide acting through the Mas receptor (MasR). Recent studies show that Ang1-7 has an antiproliferative action on lung adenocarcinoma cells. The aim of this study was to characterize RAS expression in human colon adenocarcinoma and to investigate whether Ang1-7 exerts an antiproliferative effect on human colon adenocarcinoma cells. Gene, protein expression and enzymatic activity of the main components of the RAS were determined on non-neoplastic colon mucosa as well as on the tumor mass and the mucosa taken 5 cm distant from it, both collected from patients with colon adenocarcinoma. Two different human colon cancer cell lines were treated with AngII and Ang1-7. The novel finding of this study was that MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. However, AngII and Ang1-7 did not have any pro-/antiproliferative effects in the cell lines studied. The data suggest that upregulation of the MasR could be used as a diagnostic marker of colon adenocarcinoma.

Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

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Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina

2014-08-01

We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

Inhibition of PTP1B disrupts cell?cell adhesion and induces anoikis in breast epithelial cells

OpenAIRE

Hilmarsdottir, Bylgja; Briem, Eirikur; Halldorsson, Skarphedinn; Kricker, Jennifer; Ingthorsson, S?var; Gustafsdottir, Sigrun; M?landsmo, Gunhild M; Magnusson, Magnus K; Gudjonsson, Thorarinn

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells a...

Different molecular organization of two carotenoids, lutein and zeaxanthin, in human colon epithelial cells and colon adenocarcinoma cells

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Grudzinski, Wojciech; Piet, Mateusz; Luchowski, Rafal; Reszczynska, Emilia; Welc, Renata; Paduch, Roman; Gruszecki, Wieslaw I.

2018-01-01

Two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of exogenous carotenoids, either zeaxanthin or lutein. Both carotenoids demonstrated cytotoxicity with respect to cancer cells but not to normal cells. Cells from both the cell lines were analyzed with application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. Both imaging techniques show effective incorporation of carotenoid molecules into growing cells. Comparison of the Raman scattering and fluorescence lifetime characteristics reveals different molecular organization of carotenoids in the carcinoma and normal cells. The main difference consists in a carotenoid aggregation level which is substantially lower in the carcinoma cells as compared to the normal cells. Different molecular organization of carotenoids was interpreted in terms of a different metabolism of normal and carcinoma cells and has been concluded to provide a possibility of cancer diagnosis based on spectroscopic analyses.

Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

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Celià-Terrassa, Toni

2018-05-04

Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

Mesenchymal precursor cells maintain the differentiation and proliferation potentials of breast epithelial cells

Science.gov (United States)

2014-01-01

Introduction Stromal-epithelial interactions play a fundamental role in tissue homeostasis, controlling cell proliferation and differentiation. Not surprisingly, aberrant stromal-epithelial interactions contribute to malignancies. Studies of the cellular and molecular mechanisms underlying these interactions require ex vivo experimental model systems that recapitulate the complexity of human tissue without compromising the differentiation and proliferation potentials of human primary cells. Methods We isolated and characterized human breast epithelial and mesenchymal precursors from reduction mammoplasty tissue and tagged them with lentiviral vectors. We assembled heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in corresponding monocultures by analyzing growth, differentiation potentials, and gene expression profiles. Results We show that heterotypic culture of non-immortalized human primary breast epithelial and mesenchymal precursors maintains their proliferation and differentiation potentials and constrains their growth. We further describe the gene expression profiles of stromal and epithelial cells in co-cultures and monocultures and show increased expression of the tumor growth factor beta (TGFβ) family member inhibin beta A (INHBA) in mesenchymal cells grown as co-cultures compared with monocultures. Notably, overexpression of INHBA in mesenchymal cells increases colony formation potential of epithelial cells, suggesting that it contributes to the dynamic reciprocity between breast mesenchymal and epithelial cells. Conclusions The described heterotypic co-culture system will prove useful for further characterization of the molecular mechanisms mediating interactions between human normal or neoplastic breast epithelial cells and the stroma, and will provide a framework to test the relevance of the ever-increasing number of oncogenomic alterations identified in human breast cancer. PMID:24916766

Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

International Nuclear Information System (INIS)

Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

2008-01-01

Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

Early-Onset Signet-Ring Cell Adenocarcinoma of the Colon: A Case Report and Review of the Literature

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Maliha Khan

2017-01-01

Full Text Available Colorectal cancer (CRC remains the second leading cause of cancer-related deaths in the United States. While a decline has been observed in the older population, the occurrence of CRC in the adolescent and young adult (AYA population has increased over the past two decades. The histopathologic characteristics and clinical behavior of CRC in AYA patients have been shown to be distinct from those of CRC in older adults. The rarer subtypes of CRC such as mucinous adenocarcinoma and signet-ring cell carcinoma are associated with a poorer prognosis compared to the more common subtypes. Here we report a case of a 20-year-old man who was diagnosed with stage IVB (T4 N2 M1, with peritoneal carcinomatosis signet-ring cell adenocarcinoma of the colon. The scarcity of information on these rarer subtypes merits further study and investigation.

[Killing effect of icotinib combined with CIK on human lung adenocarcinoma cells in vitro].

Science.gov (United States)

Yao, B Q; Jia, Y; Guo, J Q; Zhao, Q; Sun, H; Zhang, J P

2017-08-23

Objective: To explore the inhibitory effect of icotinib combined with cytokine induced killer (CIK) on various human lung adenocarcinoma cell lines in vitro. Methods: The inhibitory effect of icotinib alone or icotinib combined with CIK on HCC827 and A549 cells was detected by cell counting kit-8(CCK-8). The apoptosis was detected by flow cytometry via Annexin V/PI staining. The effect of icotinib on CIK phenotype was detected by flow cytometry. Results: The inhibitory rates of HCC827 cells treated with 1.5, 3, 6, 12 μmol/L icotinib were (5.64±0.05)%, (8.62±0.45)%, (14.57±0.65)% and (18.52±0.91)%, respectively. The inhibitory rates of A549 cells were (1.64±0.48)%, (2.09±0.28)%, (3.69±0.45)%, (4.41±0.58)%, respectively. At the same concentration, the inhibitory rate of HCC827 cells with icotinib treatment was significantly higher than that of A549 cells ( P icotinib was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells were (37.07±3.50)%, (76.03±6.55)%, (80.34±10.69)%, respectively, and the inhibitory rates of A549 cells were(25.72±1.41)%, (52.76±3.82)%, (62.26±1.94)%, respectively. The inhibitory rates of 6 μmol/L icotinib combined with CIK were significantly higher than those of icotinib group and CIK group alone at the same effector/target ratio ( P icotinib combined with CIK were significantly higher than those of icotinib group and blank control group ( P icotinib treatment was not significantly different from each other( P >0.05). Conclusions: EGFR mutant lung adenocarcinoma cells are more sensitive to icotinib, while the EGFR mutation status has no effect on the killing effect of CIK cells. icotinib combined with CIK has a synergistic effect on the inhibition of tumor growth, and icotinib has no any impact on the phenotype of CIK cells.

Presentation of Axillary Metastases from Occult Breast Carcinoma

Institute of Scientific and Technical Information of China (English)

Xin Wang

2007-01-01

Axillary presentation from occult breast cancer is uncommon and continues to be a diagnostic and therapeutic challenge to physicians.Once the diagnosis of adenocarcinoma metastatic to an axillary lymph node has been confirmed,a preoperative workup should be done.The current experience is based on several relatively small retrospective reviews and case reports.It is difficult to determine the best management of occult breast cancer.However,treatmenl of axillary Iymph node dissection is recommended for local control and complete staging information.Treatment of breast should be a choice between breast conservation with whole-breast radiotherapy and mastectomy.Adjuvant systemic treatment should be offered.

Bone metastasis of undifferentiated pulmonary adenocarcinoma in a cat

International Nuclear Information System (INIS)

Jensen, H.E.; Arnbjerg, J.

1986-01-01

In the cat, metastases from primary lung tumors (PLT) to distal bones have been described by Moore & Middleton (differentiated adenocarcinoma) and Pool et al. (squamous cell carcinoma) (16 22). This paper describes the radiological and pathological findings in a cat with metastatic undifferentiated papillary adenocarcinoma. The involvement of the toes was the initial sign leading to veterinary consultation

File list: Unc.Brs.50.AllAg.Breast_cancer_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Brs.50.AllAg.Breast_cancer_cells hg19 Unclassified Breast Breast cancer cells h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Brs.50.AllAg.Breast_cancer_cells.bed ...

The Controversial Clinicobiological Role of Breast Cancer Stem Cells

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Claudia Casarsa

2008-01-01

Full Text Available Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. Growing experimental evidence suggests that cancer stem cells (CSCs may contribute to tumor progression and metastasis spread. However, despite the tremendous clinical potential of such cells and their possible therapeutic management, the real nature of CSCs remains to be elucidated. Starting from what is currently known about normal mammary stem/progenitor cells, to better define the cell that originates a tumor or is responsible for metastatic spread, this review will discuss experimental evidence of breast cancer stem cells and speculate about the clinical importance and implications of their evaluation.

SRT1720 induces lysosomal-dependent cell death of breast cancer cells.

Science.gov (United States)

Lahusen, Tyler J; Deng, Chu-Xia

2015-01-01

SRT1720 is an activator of SIRT1, a NAD(+)-dependent protein and histone deacetylase that plays an important role in numerous biologic processes. Several studies have illustrated that SRT1720 treatment could improve metabolic conditions in mouse models and in a study in cancer SRT1720 caused increased apoptosis of myeloma cells. However, the effect of SRT1720 on cancer may be complex, as some recent studies have demonstrated that SRT1720 may not directly activate SIRT1 and another study showed that SRT1720 treatment could promote lung metastasis. To further investigate the role of SRT1720 in breast cancer, we treated SIRT1 knockdown and control breast cancer cell lines with SRT1720 both in vitro and in vivo. We showed that SRT1720 more effectively decreased the viability of basal-type MDA-MB-231 and BT20 cells as compared with luminal-type MCF-7 breast cancer cells or nontumorigenic MCF-10A cells. We demonstrated that SRT1720 induced lysosomal membrane permeabilization and necrosis, which could be blocked by lysosomal inhibitors. In contrast, SRT1720-induced cell death occurred in vitro irrespective of SIRT1 status, whereas in nude mice, SRT1720 exhibited a more profound effect in inhibiting the growth of allograft tumors of SIRT1 proficient cells as compared with tumors of SIRT1-deficient cells. Thus, SRT1720 causes lysosomal-dependent necrosis and may be used as a therapeutic agent for breast cancer treatment. ©2014 American Association for Cancer Research.

Treatment of Murine Tumor Models of Breast Adenocarcinoma by Continuous Dual-Frequency Ultrasound

Directory of Open Access Journals (Sweden)

Amir Hoshang Barati

2009-03-01

Full Text Available Introduction: Acoustic transient cavitation is the primary mechanism of sonochemical reaction and has potential use for tumor treatment. In this study, the in vivo anti-tumor effect of simultaneous dual-frequency ultrasound at low-level intensity (ISATA < 6 W/cm2 was investigated in a spontaneous murine model of breast adenocarcinoma in Balb/c mice. Materials and Methods: Forty tumor bearing mice were divided into four groups (10 in each group. The treated groups received 15 or 30 minutes of combined dual-frequency ultrasound in continuous mode (1 MHzcon + 150 kHzcon respectively. The control and the sham groups contained the untreated mice. The tumor growth delay parameters including tumor volume, relative tumor volume, T5 and T2 (the needed time for each tumor to reach 5 and 2 times the initial tumor volume, respectively, survival period and percent of tumor growth inhibition ratio were measured on different days after treatment. Results: The results showed that the 30 min treatment was effective in tumor growth delay and percent of tumor growth inhibitory ratio compared to the sham and the control groups. The tumor volume growth and relative volume of tumors in the same treated group showed an anti-tumor effect relative to the sham and the control groups. There was a significant difference in tumor volume growth between this 30 min treatment group and the sham group 12 days after treatment (p-value

Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma

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Liu NQ

2015-03-01

Full Text Available Naiqing Liu,1,2,* Jingyu Zhang,2,* Shuxiang Sun,2 Liguang Yang,2 Zhongjin Zhou,2 Qinli Sun,2 Jun Niu11Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 2Department of General Surgery, Yishui Central Hospital, Linyi, People’s Republic of China*These authors contributed equally to this workBackground: The clinical significance of fibroblast growth factor 1 (FGF1 has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored.Patients and methods: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan–Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma.Results: Higher FGF1 expression rate is 56.7% (101/178 in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001. Expression of FGF1 is significantly associated with lymph node invasion (P<0.001, distant metastasis (P=0.013, and differentiation (P=0.015. Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021, and can be identified to be an independent unfavorable prognostic factor (P=0.004.Conclusion: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.Keywords: fibroblast growth factor 1, gastric adenocarcinoma, prognosis, biomarker, lymph node, gene fusion

Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells.

Science.gov (United States)

Zhang, Jianxiang; Ma, Yanmei; Wang, Shoujun; Chen, Fu; Gu, Yuanting

2016-06-01

Breast cancer is the most common malignancy in women around the world, and its incidence and mortality rates are still rising. An increasing number of studies have reported that SOX18 plays an important role in various cancers. However, the role of SOX18 in breast cancer remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of SOX18 in breast cancer. We found that the mRNA and protein expression levels of SOX18 were prevalently and significantly overexpressed in human breast cancer cell lines. Next, we performed loss-of-function experiments by transfection of two breast cancer cell lines, BT-474 and MCF-7, with SOX18 small interfering RNAs (siRNA). Results showed that SOX18 siRNA transfection significantly suppressed mRNA and protein expression of SOX18 in breast cancer cells. Furthermore, knockdown of SOX18 significantly inhibited cell proliferation and invasion, but promoted apoptosis in breast cancer cells. Importantly, several oncogenic proteins, including the Ras homolog gene family member A (RhoA), platelet-derived growth factor B (PDGFB), Insulin-like growth factor 1 receptor (IGF-1R), and matrix metalloproteinase-7 (MMP-7), were markedly decreased by SOX18 siRNA. Taken together, the results of our study suggest that knockdown of SOX18 inhibits breast cancer cell growth and invasion, possibly by downregulating downstream oncogenic proteins, providing novel insights into the development of breast cancer therapy through targeting of SOX18.

Cell membrane softening in human breast and cervical cancer cells

Science.gov (United States)

Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

2015-08-01

Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

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Radiosensitivity of a monoclonal human lung adenocarcinoma cell line with MDR phenotype induced by CDDP: an in vitro study

International Nuclear Information System (INIS)

Zhang Junxiang; Kong Zhaolu; Shen Zhifen; Tong Shungao; Jin Yizun

2006-01-01

The study was to evaluate radiosensitivity of a monoclonal human lung adenocarcinoma cell line SPC-A-1/CDDP-4 with MDR phenotype induced by cisplatin (CDDP) compared with its parental cell SPC-A-1 in vitro. The glutathione (GSH) content and the radiosensitivity of SPC-A-1/CDDP-4 and SPC-A-1 cells were investigated in aerobic and under hypoxia, respectively. The radiosensitization effect of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, to SPC-A-1/CDDP-4 and SPC-A-1 cells was observed. The results indicated that the monoclonal human lung adenocarcinoma cell line SPC-A-1/CDDP-4 showed, to some extent, a cross-resistance to 137 Cs γ-ray, in addition to its resistance to anticancer drugs (CDDP, ADM, MTX and VCR). The GSH content of SPC-A-1/CDDP-4 cells was higher than that of SPC-A-1 cells both in aerobic and under hypoxia which might account for it. BSO had radiosensitization effect to SPC-A-1/CDDP-4 and SPC-A-1 cells both in aerobic and under hypoxia, but it was stronger under hypoxia than in aerobic and it was stronger to SPC-A-1/CDDP-4 cells than to SPC-A-1 cells. (authors)

Spindle Cell Metaplastic Breast Cancer: Case Report

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Dursun Ozgur Karakas

2013-08-01

Conclusion: Spindle cell metaplastic breast cancer must be considered in differential diagnosis of breast cancers, and preoperative immunohistochemical examination, including cytokeratin and vimentin, must be added to pathological examination in intervening cases. [Arch Clin Exp Surg 2013; 2(4.000: 259-262

Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.

Science.gov (United States)

Colacino, Justin A; McDermott, Sean P; Sartor, Maureen A; Wicha, Max S; Rozek, Laura S

2016-07-01

Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

Molecular characterization of breast cancer cell lines through multiple omic approaches.

Science.gov (United States)

Smith, Shari E; Mellor, Paul; Ward, Alison K; Kendall, Stephanie; McDonald, Megan; Vizeacoumar, Frederick S; Vizeacoumar, Franco J; Napper, Scott; Anderson, Deborah H

2017-06-05

Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated. We determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer. The cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated

Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

2013-05-10

Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

Adenocarcinoma of the urinary bladder, mesonephroid type: a rare case

Directory of Open Access Journals (Sweden)

Mahmoud Abbas

2013-02-01

Full Text Available Primary adenocarcinoma of the urinary bladder is a rare disease. It occurs in 0.5-2% of all bladder cancers and is discussed as the malignant counterpart of nephrogenic adenomas. We report a 46-year-old white female presented with gross hematuria for clinical examination. Histopathology revealed pT2, Pn1, L1, G2 adenocarcinoma of the bladder and carcinoma in situ according to the TNM classification. Computed tomography scan diagnostic was unremarkable. Patients with adenocarcinoma of the urinary bladder should be treated vigorously and without time delay. Only 7 cases of adenocarcinoma in the urinary bladder (mesonephroid have been described until now. We present a case of clear cell adenocarcinoma of the urinary bladder, mesonephroid type that early diagnosed and till now 3 months after the cystectomy without symptoms and without complications.

Primary adenocarcinoma of lung: A pictorial review of recent updates

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Gaikwad, Anand, E-mail: anandgaik@yahoo.co.in [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gupta, Ashish, E-mail: ashgupta@toh.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Hare, Sam, E-mail: samanjeet@btinternet.com [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gomes, Marcio, E-mail: mgomes@toh.on.ca [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Sekhon, Harman, E-mail: hsekhon@toh.on.ca [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Souza, Carolina, E-mail: csouza@ottawahospital.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Inacio, Joao, E-mail: joao.r.inacio@gmail.com [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Lad, Shilpa, E-mail: slad@toh.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Seely, Jean, E-mail: jeseely@ottawahospital.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada)

2012-12-15

Primary adenocarcinoma of lung has replaced squamous cell carcinoma as the commonest histological subtype of lung cancer and the incidence of primary lung adenocarcinoma appears to be rising. Although the main factors behind this ‘epidemic-like’ situation are largely undiscovered, filter cigarettes appear to significantly contribute to this shift in the histopathological spectrum. The new multidisciplinary classification of adenocarcinoma of lung was introduced to address advances in clinical, pathological, radiological and molecular sciences. The purpose of this essay is to discuss various classes of lung adenocarcinoma in the new classification with their classical imaging features on computed tomography and summarise the recent advances in the field of radiology and review radiology recommendations.

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology

DEFF Research Database (Denmark)

Popat, Sanjay; Mellemgaard, Anders; Reck, Martin

2017-01-01

PATIENTS & METHODS: We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer. RESULTS: Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel...

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The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

Directory of Open Access Journals (Sweden)

Ginsburg Erika

2010-05-01

Full Text Available Abstract Background Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM derived from premenopausal African-American (AA or Caucasian-American (CAU breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women. Methods The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry. Results Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER-, progesterone receptor (PR/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1

ERβ inhibits proliferation and invasion of breast cancer cells

Science.gov (United States)

Lazennec, Gwendal; Bresson, Damien; Lucas, Annick; Chauveau, Corine; Vignon, Françoise

2001-01-01

Recent studies indicate that the expression of ERβ in breast cancer is lower than in normal breast, suggesting that ERβ could play an important role in carcinogenesis. To investigate this hypothesis, we engineered estrogen-receptor negative MDA-MB-231 breast cancer cells to reintroduce either ERα or ERβ protein with an adenoviral vector. In these cells, ERβ (as ERα) expression was monitored using RT-PCR and Western blot. ERβ protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of estradiol. ERβ and ERα induced the expression of several endogenous genes such as pS2, TGFα or the cyclin kinase inhibitor p21, but in contrast to ERα, ERβ was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ERα and ERβ estrogen-induced activities. ERβ inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ERα inhibition of proliferation is hormone-dependent. Moreover, ERβ and ERα, decreased cell motility and invasion. Our data bring the first evidence that ERβ is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ERβ expression could be one of the events leading to the development of breast cancer. PMID:11517191

Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

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Masoud Hashemi Arabi

2014-05-01

Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

Primary Rectal Adenocarcinoma Metastasizing to Bilateral Breast - a Rare Case Demonstrated by {sup 18}F-FDG PET/CT

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Soundararajan, Ramya; Arora, Saurabh; Das, Chandan Jyoti; Roy, Maitrayee; Kumar, Rakesh; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)

2016-06-15

A 22-year-old female presented with multiple painless bilateral breast masses for the past 2 months. On Further questioning she had hematochezia and constipation for three months. On digital rectal examination, thickening of rectal mucosa at 5 cm from the anal verge was found. On physical examination, multiple firm, non-tender, nodular lesions were found in bilateral breasts. Metastatic breast disease from extra mammary primaries is uncommon and it constitutes 0.5 - 6% of all breast malignancies. melanomas, lymphomas, leukemias, ands sarcomas are the most common malignancies causing breast metastases. Infrequently, carcinomas of the lung, stomach, ovary, liver, tonsil, pleura, pancreas, cervix, perineum, endometrium, bladder, carcinoid tumors and renal cell carcinomas can cause metastatic breast disease. Metastatic breast disease from colorectal cancer is characterised by disseminated metastatic disease and a poor prognosis. In this case, It was essential to distinguish between metastatic breast disease primary breast carcinoma to plan appropriate management. Because of its rare incidence and high index of clinical suspicion, appropriate radiological investigations and histopathology is essential for accurate diagnosis. {sup 18}F-FDG PET/CT, being a whole-body metabolic functional imaging modality, helped us determine the extent of the primary and metastatic disease. In view of disseminated metastases, the bilateral breast disease was also considered as metastatic involvement, Which was proven by histopathology.

Hepatoid Adenocarcinoma of the Urachus

Directory of Open Access Journals (Sweden)

Daniel Fernando Gallego

2016-01-01

Full Text Available Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis.

Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review.

Science.gov (United States)

Liu, Yangyang

2018-06-03

Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR-mutant patients. However, these patients inevitably come cross acquired resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs. The present case concerns a case of a 38-year-old man presenting with cough and dyspnea. Radical resection was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient suffered pleural metastasis after successful treatment with surgery and adjuvant treatment. So, erlotinib was administered with 18 months. Because of enlarged pleural nodule, repeat biopsy identified an SCLC and chemotherapy was started. However, despite the brief success of chemotherapy, our patient suffered brain metastasis. Our case emaphsizes both the profile of transformation from NSCLC to SCLC and the importance of repeat biopsy dealing with drug resistance. We also summarize the clinical characteristics, mechanisms, predictors of SCLC transformation, treatment after transformation and other types of transformation to SCLC.

APC selectively mediates response to chemotherapeutic agents in breast cancer

International Nuclear Information System (INIS)

VanKlompenberg, Monica K.; Bedalov, Claire O.; Soto, Katia Fernandez; Prosperi, Jenifer R.

2015-01-01

The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated or hypermethylated in up to 70 % of sporadic breast cancers depending on subtype; however, the effects of APC mutation on tumorigenic properties remain unexplored. Using the Apc Min/+ mouse crossed to the Polyoma middle T antigen (PyMT) transgenic model, we identified enhanced breast tumorigenesis and alterations in genes critical in therapeutic resistance independent of Wnt/β-catenin signaling. Apc mutation changed the tumor histopathology from solid to squamous adenocarcinomas, resembling the highly aggressive human metaplastic breast cancer. Mechanistic studies in tumor-derived cell lines demonstrated that focal adhesion kinase (FAK)/Src/JNK signaling regulated the enhanced proliferation downstream of Apc mutation. Despite this mechanistic information, the role of APC in mediating breast cancer chemotherapeutic resistance is currently unknown. We have examined the effect of Apc loss in MMTV-PyMT mouse breast cancer cells on gene expression changes of ATP-binding cassette transporters and immunofluorescence to determine proliferative and apoptotic response of cells to cisplatin, doxorubicin and paclitaxel. Furthermore we determined the added effect of Src or JNK inhibition by PP2 and SP600125, respectively, on chemotherapeutic response. We also used the Aldefluor assay to measure the population of tumor initiating cells. Lastly, we measured the apoptotic and proliferative response to APC knockdown in MDA-MB-157 human breast cancer cells after chemotherapeutic treatment. Cells obtained from MMTV-PyMT;Apc Min/+ tumors express increased MDR1 (multidrug resistance protein 1), which is augmented by treatment with paclitaxel or doxorubicin. Furthermore MMTV-PyMT;Apc Min/+ cells are more resistant to cisplatin and doxorubicin-induced apoptosis, and show a larger population of ALDH positive cells. In the human metaplastic breast cancer cell line MDA-MB-157, APC knockdown led to paclitaxel and cisplatin

Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

Science.gov (United States)

Chang, Hsin-Yi; Li, Ming-Hua; Huang, Tsui-Chin; Hsu, Chia-Lang; Tsai, Shang-Ru; Lee, Si-Chen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

2015-02-06

Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 μm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

Low-risk susceptibility alleles in 40 human breast cancer cell lines

International Nuclear Information System (INIS)

Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

2009-01-01

Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

Directory of Open Access Journals (Sweden)

Tim A D Smith

Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

Ureteric stricture secondary to unusual extension of prostatic adenocarcinoma.

Science.gov (United States)

Chalasani, Venu; Macek, Petr; O'Neill, Gordon F; Barret, Wade

2010-02-01

This article describes an unusual finding in a patient who presented with an adenocarcinoma of the prostate and right hydronephrosis. A 68-year-old male presented with right hydronephrosis and a PSA of 96. DRE was consistent with cT3 carcinoma. Cystoscopy showed an exophytic superficial transitional cell carcinoma (TCC) of the bladder and a transrectal biopsy of the prostate confirmed adenocarcinoma Gleason score 4+3. Staging investigations (CT pelvis and bone scan) were negative; androgen deprivation therapy was therefore initiated for the prostatic adenocarcinoma. Upper tract imaging showed multiple filling defects in the proximal ureter. Ureteroscopy showed a stricture at the level of the iliac vessels. With a working diagnosis of upper tract TCC, right open nephroureterectomy was performed. Final histology showed prostatic adenocarcinoma infiltrating the adventitia of the entire ureter up to the level of the renal pelvis. A rare cause of ureteric stricture, contiguous spread of prostatic adenocarcinoma, should be considered in the differential diagnosis of patients presenting with upper tract obstruction and a known history of prostatic adenocarcinoma. Androgen deprivation therapy for several months did not seem to cause resolution of the tumor in the periureteric, ureteric and perihilar tissues.

Necrosis - the dominant form of cell death after phototoxicity impact of hypericin in colon adenocarcinoma cells HT29

International Nuclear Information System (INIS)

Mikes, J.; Kleban, J.; Sackova, V.; Solar, P.; Fedorocko, P.

2006-01-01

Photodynamic therapy (PDT) is a therapeutical approach for the treatment of malignant as well as non-malignant disorders based on administration of nontoxic/weakly toxic photosensitive compound and its activation with light. Hypericin, one of the promising photosensitizers, is known to induce apoptosis with high efficiency in various cell line models. However, here we report the prevalence of necrosis in colon adenocarcinoma HT-29 cells exposed to an extensive range of PDT doses evoked by variations in two variables - hypericin concentration and light dose. Necrosis was the principal mode of cell death despite different PDT doses and the absence of anti-apoptotic Bcl-2 expression. It is likely that the mutation in p53 plays a crucial role in cell death signaling in HT-29. Data indicating proliferation shifting in HT29 cells, incidence of cell death (apoptosis, necrosis and secondary necrosis) and comparison of cytotoxicity and caspase-3 activity of HT29 with HeLa cells are presented. (authors)

Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

Science.gov (United States)

Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

2015-12-01

Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dissection of a stem cell hierarchy in the human breast

DEFF Research Database (Denmark)

Rubner Fridriksdottir, Agla Jael

and apoptosis during each menstrual cycle. These changes are most prominent during pregnancy, lactation and involution after breast feeding. These highly dynamic changes are thought to rely on the presence of a breast epithelial stem cell population (reviewed in (Fridriksdottir et al. 2005)). Nevertheless......, cellular pathways that contribute to adult human breast gland architecture and cell lineages have not been described. Here, I identify a candidate stem cell niche in ducts, and zones containing progenitor cells in lobules (Villadsen and Fridriksdottir et al. 2007). Putative stem cells residing in ducts......-rich extracellular matrix gel. Staining for the epithelial lineage markers, cytokeratins K14 and K19, further reveals multipotent cells in the stem cell zone and three lineage- restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites...

Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

DEFF Research Database (Denmark)

Lim, Hooi Ching; Multhaupt, Hinke A. B.; Couchman, John R.

2015-01-01

breast carcinoma. This may derive from their regulation of cell adhesion, but roles for specific syndecans are unresolved. Methods: The MDA-MB231 human breast carcinoma cell line was exposed to exogenous glycosaminoglycans and changes in cell behavior monitored by western blotting, immunocytochemistry......, invasion and collagen degradation assays. Selected receptors including PAR-1 and syndecans were depleted by siRNA treatments to assess cell morphology and behavior. Immunohistochemistry for syndecan-2 and its interacting partner, caveolin-2 was performed on human breast tumor tissue arrays. Two......-tailed paired t-test and one-way ANOVA with Tukey¿s post-hoc test were used in the analysis of data. Results: MDA-MB231 cells were shown to be highly sensitive to exogenous heparan sulfate or heparin, promoting increased spreading, focal adhesion and adherens junction formation with concomitantly reduced...

The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma

LENUS (Irish Health Repository)

Keld, Richard

2010-12-09

Abstract Background Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers. Results Here, we have studied the expression of the PEA3 subfamily members PEA3\\/ETV4 and ER81\\/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. Conclusions This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.

Chlorpyrifos promotes colorectal adenocarcinoma H508 cell growth through the activation of EGFR/ERK1/2 signaling pathway but not cholinergic pathway.

Science.gov (United States)

Suriyo, Tawit; Tachachartvanich, Phum; Visitnonthachai, Daranee; Watcharasit, Piyajit; Satayavivad, Jutamaad

2015-12-02

Aside from the effects on neuronal cholinergic system, epidemiological studies suggest an association between chlorpyrifos (CPF) exposure and cancer risk. This in vitro study examined the effects of CPF and its toxic metabolite, chlorpyrifos oxon (CPF-O), on the growth of human colorectal adenocarcinoma H508, colorectal adenocarcinoma HT-29, normal colon epithelial CCD841, liver hepatocellular carcinoma HepG2, and normal liver hepatocyte THLE-3 cells. The results showed that CPF (5-100 μM) concentration-dependently increased viability of H508 and CCD841 cells in serum-free conditions. This increasing trend was not found in HT-29, HepG2 and THLE-3 cells. In contrast, CPF-O (50-100 μM) reduced the viability of all cell lines. Cell cycle analysis showed the induction of cells in the S phase, and EdU incorporation assay revealed the induction of DNA synthesis in CPF-treated H508 cells indicating that CPF promotes cell cycle progression. Despite the observation of acetylcholinesterase activity inhibition and reactive oxygen species (ROS) generation, atropine (a non-selective muscarinic acetylcholine receptor antagonist) and N-acetylcysteine (a potent antioxidant) failed to inhibit the growth-promoting effect of CPF. CPF increased the phosphorylation of epidermal growth factor receptor (EGFR) and its downstream effector, extracellular signal regulated kinase (ERK1/2), in H508 cells. AG-1478 (a specific EGFR tyrosine kinase inhibitor) and U0126 (a specific MEK inhibitor) completely mitigated the growth promoting effect of CPF. Altogether, these results suggest that EGFR/ERK1/2 signaling pathway but not cholinergic pathway involves in CPF-induced colorectal adenocarcinoma H508 cell growth. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pancreatic Polypeptide Cell Proliferation in the Pancreas and Duodenum Coexisting in a Patient With Pancreatic Adenocarcinoma Treated With a GLP-1 Analog.

Science.gov (United States)

Talmon, Geoffrey A; Wren, J David; Nguyen, Christophe L; Pour, Parviz M

2017-07-01

A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells. Among the etiological factors, the possible long-lasting effects of the GLP-1 analog, with which the patient was treated, are discussed. This is the first report in the literature of both the coexistence of a pancreatic adenocarcinoma and invasive PPoma and the occurrence of PP and insulin cells in human duodenal mucosa.

Urothelial-Type adenocarcinoma of the prostate mimicking metastatic colorectal adenocarcinoma

Directory of Open Access Journals (Sweden)

Brian P. Adley

2006-12-01

Full Text Available Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.

An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

Science.gov (United States)

Cilekar, Murat; Erkasap, Serdar; Oner, Ulku; Akici, Murat; Ciftci, Evrim; Dizen, Hayrettin; Turel, Serkan; Kavak, Ozgu I; Yilmaz, Sezgin

2015-01-01

Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

Science.gov (United States)

Beausang, John F; Wheeler, Amanda J; Chan, Natalie H; Hanft, Violet R; Dirbas, Frederick M; Jeffrey, Stefanie S; Quake, Stephen R

2017-11-28

Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment. Copyright © 2017 the Author(s). Published by PNAS.

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

Directory of Open Access Journals (Sweden)

Yurgel VC

2014-03-01

Full Text Available Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas11Programa de Pós-Graduação em Biotecnologia (PPGB, Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 4Centro de Nanociência e Nanotecnologia, CNANO-UFRGS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil*These authors contributed equally to this workAbstract: Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt2] and MTX(OEt2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt2 solution and MTX(OEt2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231

Nifedipine promotes the proliferation and migration of breast cancer cells.

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Dong-Qing Guo

Full Text Available Nifedipine is widely used as a calcium channel blocker (CCB to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3. Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.

H19 lncRNA mediates 17β-estradiol-induced cell proliferation in MCF-7 breast cancer cells.

Science.gov (United States)

Sun, Hong; Wang, Guo; Peng, Yan; Zeng, Ying; Zhu, Qiong-Ni; Li, Tai-Lin; Cai, Jia-Qin; Zhou, Hong-Hao; Zhu, Yuan-Shan

2015-06-01

Estrogen plays a critical role in breast cancer development and progression. However, the mechanism involved in the promotion of breast cancer development and progression by estrogen remains unclear although it has been intensively studied. In the present study, we investigated the estrogen inducibility and functional significance of H19 lncRNA in breast cancer cells and tumor tissues. The screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19 lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer cells than in ER-negative MDA-MB-231 cells. 17β-estradiol produced a dose- and time-dependent induction of H19 expression in MCF-7 cells, which was mediated via ERα as evident by the blockade of this 17β-estradiol effect with ICI 182780, a specific ER antagonist and knockdown of ERα using specific RNAi. Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen-induced cell growth while overexpression of H19 lncRNA stimulated cell proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER-negative tumor tissues. These results suggest that H19 is an estrogen-inducible gene and plays a key role in cell survival and in estrogen-induced cell proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker for breast cancer diagnosis and progression, and as a valuable target for breast cancer therapy.

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An Exceptional Adenocarcinoma in a Girl

Directory of Open Access Journals (Sweden)

Bangaly Traore

2018-01-01

Full Text Available Anal adenocarcinoma is very rare and usually occurs in the elderly. We present a case of a 12-year-old girl with an anal margin painful tumor infiltrating the lower rectum, with perineal and vulvar permeation nodules and bilateral fixed inguinal and iliac lymph nodes. Histology showed anal adenocarcinoma with mucosecreting component and independent cells. She had no extra pelvic metastasis on CT scan. She underwent a colostomy and palliative care. This exceptional case challenges us on the diversity of forms of anal cancers that require a multidisciplinary approach. The precarious social context and the age of onset make it difficult to manage this rare cancer.

Breast cancer instructs dendritic cells to prime interleukin 13–secreting CD4+ T cells that facilitate tumor development

Science.gov (United States)

Aspord, Caroline; Pedroza-Gonzalez, Alexander; Gallegos, Mike; Tindle, Sasha; Burton, Elizabeth C.; Su, Dan; Marches, Florentina; Banchereau, Jacques; Palucka, A. Karolina

2007-01-01

We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417–1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon γ) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid β2 microglobulin–deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development. PMID:17438063

Do myoepithelial cells hold the key for breast tumorprogression?

Energy Technology Data Exchange (ETDEWEB)

Polyak, Kornelia; Hu, Min

2005-11-18

Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.

A therapeutic and diagnostic dilemma: granular cell tumor of the breast.

Science.gov (United States)

Pergel, Ahmet; Yucel, Ahmet Fikret; Karaca, A Serdar; Aydin, Ibrahim; Sahin, Dursun Ali; Demirbag, Nilgun

2011-01-01

Six to eight percent of granular cell tumors are seen in the breast. Although mostly benign, they rarely have malignant features clinically and radiologically reminding of breast cancer. This may lead to a potential misdiagnosis of breast carcinoma and overtreatment of patients. The final diagnosis is made by immunohistochemical examination. We performed excisional biopsy on a patient who was diagnosed to have a breast mass. The histopathological examination of the mass revealed granular cell tumor.

Novel anticancer activity of phloroglucinol against breast cancer stem-like cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Rae-Kwon; Uddin, Nizam [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Hyun, Jin-Won [College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756 (Korea, Republic of); Kim, Changil [Department of Biotechnology, Konkuk University, Chungju 380-701 (Korea, Republic of); Suh, Yongjoon, E-mail: hiswork@hanmail.net [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae, E-mail: sj0420@hanyang.ac.kr [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

2015-08-01

Poor prognosis of breast cancer patients is closely associated with metastasis and relapse. There is substantial evidence supporting that cancer stem-like cells (CSCs) are primarily responsible for relapse in breast cancer after anticancer treatment. However, there is a lack of suitable drugs that target breast cancer stem-like cells (BCSCs). Here, we report that phloroglucinol (PG), a natural phlorotannin component of brown algae, suppresses sphere formation, anchorage-independent colony formation and in vivo tumorigenicity. In line with these observations, treatment with PG also decreased CD44{sup +} cancer cell population as well as expression of CSC regulators such as Sox2, CD44, Oct4, Notch2 and β-catenin. Also, treatment with PG sensitized breast cancer cells to anticancer drugs such as cisplatin, etoposide, and taxol as well as to ionizing radiation. Importantly, PG inhibited KRAS and its downstream PI3K/AKT and RAF-1/ERK signaling pathways that regulate the maintenance of CSCs. Taken together, our findings implicate PG as a good candidate to target BCSCs and to prevent the disease relapse. - Highlights: • Phloroglucinol suppresses in vivo tumor formation. • Phloroglucinol sensitizes breast cancer cells to anticancer agents. • Phloroglucinol inhibits breast cancer stem-like cells. • Phloroglucinol inhibits PI3K/AKT and KRAS/RAF/ERK signaling pathways.

Immunohistochemical assessment of NY-ESO-1 expression in esophageal adenocarcinoma resection specimens.

Science.gov (United States)

Hayes, Stephen J; Hng, Keng Ngee; Clark, Peter; Thistlethwaite, Fiona; Hawkins, Robert E; Ang, Yeng

2014-04-14

To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas. A retrospective search of our tissue archive for esophageal resection specimens containing esophageal adenocarcinoma was performed, for cases which had previously been reported for diagnostic purposes, using the systematised nomenclature of human and veterinary medicine coding system. Original haematoxylin and eosin stained sections were reviewed, using light microscopy, to confirm classification and tumour differentiation. A total of 27 adenocarcinoma resection specimens were then assessed using immunohistochemistry for NY-ESO-1 expression: 4 well differentiated, 14 moderately differentiated, 4 moderate-poorly differentiated, and 5 poorly differentiated. Four out of a total of 27 cases of esophageal adenocarcinoma examined (15%) displayed diffuse cytoplasmic and nuclear expression for NY-ESO-1. They displayed a heterogeneous and mosaic-type pattern of diffuse staining. Diffuse cytoplasmic staining was not identified in any of these structures: stroma, normal squamous epithelium, normal submucosal gland and duct, Barrett's esophagus (goblet cell), Barrett's esophagus (non-goblet cell) and high grade glandular dysplasia. All adenocarcinomas showed an unexpected dot-type pattern of staining at nuclear, paranuclear and cytoplasmic locations. Similar dot-type staining, with varying frequency and size of dots, was observed on examination of Barrett's metaplasia, esophageal submucosal gland acini and the large bowel negative control, predominantly at the crypt base. Furthermore, a prominent pattern of apical (luminal) cytoplasmic dot-type staining was observed in some cases of Barrett's metaplasia and also adenocarcinoma. A further morphological finding of interest was noted on examination of haematoxylin and eosin stained sections, as aggregates of lymphocytes were consistently noted to surround submucosal glands. We have demonstrated for the first time NY-ESO-1 expression by esophageal

Mastic Oil Inhibits the Metastatic Phenotype of Mouse Lung Adenocarcinoma Cells

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Loutrari, Heleni; Magkouta, Sophia; Papapetropoulos, Andreas; Roussos, Charis

2011-01-01

Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC). However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01–0.04% v/v): (a) abrogated their Matrigel invasion and migration capabilities in transwell assays; (b) reduced the levels of secreted MMP-2; (c) restricted phorbol ester-induced actin remodeling and (d) limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis

Degradation of endothelial basement membrane by human breast cancer cell lines

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Yee, C.; Shiu, R.P.

1986-01-01

During metastasis, it is believed that tumor cells destroy the basement membrane (BM) of blood vessels in order to disseminate through the circulatory system. By radioactively labeling the extracellular matrix produced by primary endothelial cells in vitro, the ability of human breast cancer cells to degrade BM components was studied. We found that T-47D, a human breast cancer line, was able to degrade significant amounts of [35S]methionine-labeled and [3H]proline-labeled BM, but not 35SO4-labeled BM. Six other tumor cell lines of human breast origin were assayed in the same manner and were found to degrade BM to varying degrees. Several non-tumor cell lines tested showed relatively little degrading activity. The use of serum-free medium greatly enhanced degradation of the BM by tumor cells, suggesting a role for naturally occurring enzyme inhibitors in the serum. Direct cell contact with the BM was required for BM degradation, suggesting that the active enzymes are cell associated. The addition of hormones implicated in the etiology of breast cancer did not significantly alter the ability of T-47D cells to degrade the BM. The use of this assay affords future studies on the mechanism of invasion and metastasis of human breast cancer

P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

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Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A

2017-11-23

The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

Sensitivity of breast cancer cell lines to recombinant thiaminase I.

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Liu, Shuqian; Monks, Noel R; Hanes, Jeremiah W; Begley, Tadhg P; Yu, Hui; Moscow, Jeffrey A

2010-05-01

We have previously shown that the expression of the thiamine transporter THTR2 is decreased sevenfold in breast cancer, which may leave breast cancer cells vulnerable to acute thiamine starvation. This concept was supported by the observation that MDA231 breast cancer xenografts demonstrated growth inhibition in mice fed a thiamine-free diet. We purified recombinant Bacillus thiaminolyticus thiaminase I enzyme, which digests thiamine, to study acute thiamine starvation in breast cancer. Thiaminase I enzyme was cytotoxic in six breast cancer cell lines with IC(50)s ranging from 0.012 to 0.022 U/ml. The growth inhibitory effects of the combination of thiaminase I with either doxorubicin or paclitaxel were also examined. Over a wide range of drug concentrations, thiaminase 1 was consistently synergistic or additive with doxorubicin and paclitaxel in MCF-7, ZR75, HS578T and T47D cell lines, with most combinations having a calculated combination index (CI) of less than 0.8, indicating synergy. Although thiaminase I exposure did not stimulate the energy-sensing signaling kinases AKT, AMPK and GSK-3beta in MCF-7, ZR75, HS578T and T47D cell lines, thiaminase I exposure did stimulate expression of the ER stress response protein GRP78. In summary, thiaminase I is cytotoxic in breast cancer cell lines and triggers the unfolded protein response. These findings suggest that THTR2 down-regulation in breast tumors may present a nutritional vulnerability that could be exploited by thiaminase I enzyme therapy.

Primary male neuroendocrine adenocarcinoma involving the nipple simulating Merkel cell carcinoma - a diagnostic pitfall.

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Mecca, Patricia; Busam, Klaus

2008-02-01

Male breast cancer is a rare entity accounting for Nipple skin/subcutaneous tumors in men are even rarer. Likewise, true neuroendocrine carcinoma of the breast, defined as > 50% of tumor cells staining for either chromogranin or synaptophysin, is not a common entity, usually occurring in older women. We present the case of a 70-year-old man with a slowly growing nipple mass that had enlarged over the previous 1.5 years. The histology consisted of nests, trabeculae and sheets of basaloid cells with rare abortive gland formation and a pushing edge. The case was originally misdiagnosed as a Merkel cell carcinoma, based largely on histologic morphology. Strong staining for synaptophysin (in greater than 50% of cells), CD56, keratins AE1 : AE3 and Cam 5.2, as well as estrogen receptor and progesterone receptor was noted. Myoepithelial cells within in situ areas were identified using stains for calponin and 4A4, supporting a primary mammary duct origin. Additionally, a substantial portion of cells stained for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), confirming some overlap with sweat duct differentiation. To the best of our knowledge, although reported in the male breast, no case of primary nipple neuroendocrine carcinoma in a male patient has been reported in the literature. The gender of the patient and association with the skin of the chest wall probably contributed to the original misdiagnosis of Merkel cell carcinoma in this patient.

Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

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Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

2018-05-03

Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

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Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

2014-01-01

Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (PAvocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients

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Ruo-Chia Tseng

2009-08-01

Full Text Available A HIC1-SIRT1-p53 circular loop in which hypermethylation in cancer 1 (HIC1 represses the transcription of SIRT1 that deacetylates and inactivates p53 thus leading to HIC1 inactivation has been identified in cell and animal models. However, the alteration and prognostic effects of HIC1-SIRT1-p53 circular loop have never been demonstrated in human cancer patients. We examine the HIC1-SIRT1-p53 alterations in 118 lung cancer patients to define their etiological roles in tumorigenesis. We found that patients with lung squamous cell carcinoma with low p53 acetylation and SIRT1 expression mostly showed low HIC1 expression, confirming deregulation of HIC1-SIRT1-p53 circular loop in the clinical model. Interestingly, the expression of deleted in breast cancer 1 (DBC1, which blocks the interaction between SIRT1 deacetylase and p53, led to acetylated p53 in patients with lung adenocarcinoma. However, epigenetic alteration of HIC1 promoter by posttranslational modifications of histones and promoter hypermethylation favoring the compacted chromatin production attenuated the transcriptional induction by acetylated p53. Importantly, lung cancer patients with altered HIC1-SIRT1-p53 circular regulation showed poor prognosis. Our data show the first valid clinical evidence of the deregulation of HIC1-SIRT1-p53 loop in lung tumorigenesis and prognosis. Distinct status of p53 acetylation/deacetylation and HIC1 alteration mechanism result from different SIRT1-DBC1 control and epigenetic alteration in lung squamous cell carcinoma and lung adenocarcinoma.

Preliminary Study on the Effect of Adipocytes on the Biological Behaviors of
Lung Adenocarcinoma A549 Cells in Tumor Microenvironment

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Hang ZHANG

2018-05-01

Full Text Available Background and objective Adipocytes in the tumor microenvironment may provide the metabolic fuel or signal transduction through media and other means to promote a variety of malignant proliferation and invasion, of tumor cells, but their role in lung cancer progression is still unclear. The purpose of this study was to investigate the effect of adipocytes on lung cancer cell biology. Methods 3T3-L1 pre-adipocytes were induced into mature adipocytes. The cell morphology was observed by microscopy and Oil Red O staining. MTT assay, colony formation assay, wound-healing and Transwell methods were used to detect lung cancer cell proliferation, migration and invasion ability. The content of triglyceride in cells was determined by colorimetry. Results The morphology of lung adenocarcinoma A549 cells became more slender after co-culture with mature adipocytes, and the proliferation and cloning ability were significantly enhanced (P<0.05. In addition, mature adipocytes can also promote the migration ability (P<0.05, invasion ability (P<0.01 and accumulation of intracellular lipid (P<0.05 of A549 cells. Conclusion These findings suggested that adipocytes in tumor microenvironment can promote the proliferation, migration and invasion of lung adenocarcinoma A549 cells, which may be related to lipid metabolism.

A Therapeutic and Diagnostic Dilemma: Granular Cell Tumor of the Breast

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Ahmet Pergel

2011-01-01

Full Text Available Six to eight percent of granular cell tumors are seen in the breast. Although mostly benign, they rarely have malignant features clinically and radiologically reminding of breast cancer. This may lead to a potential misdiagnosis of breast carcinoma and overtreatment of patients. The final diagnosis is made by immunohistochemical examination. We performed excisional biopsy on a patient who was diagnosed to have a breast mass. The histopathological examination of the mass revealed granular cell tumor.

Epigenetic reprogramming of breast cancer cells with oocyte extracts

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Kumari Rajendra

2011-01-01

Full Text Available Abstract Background Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis. Results We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. Conclusions This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.

[Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro].

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Peng, Li; Li, Fu-Xi; Shao, Wen-Feng; Xiong, Jing-Bo

2013-10-01

To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms. Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR. TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres. TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells

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Li, Zanhua [Medical School of Nanchang University (China); The Chest Hospital of Jiangxi Province Department of Respiration (China); Jiang, Xunsheng [Department of Respiration, Medical School of Nanchang University (China); Zhang, Wei, E-mail: weizhangncu@gmail.com [Department of Respiration, The First Affiliated Hospital of Nanchang University (China)

2016-01-29

Recent studies suggest that the human trophoblast cell-surface antigen TROP2 is highly expressed in a number of tumours and is correlated with poor prognosis. However, its role in non-small cell lung carcinoma (NSCLC) remains largely unknown. Here we examined TROP2 expression by immunohistochemistry in a series of 68 patients with adenocarcinoma (ADC). We found significantly elevated TROP2 expression in ADC tissues compared with normal lung tissues (P < 0.05), and TROP2 overexpression was significantly associated with TNM (tumour, node, metastasis) stage (P = 0.012), lymph node metastasis (P = 0.038), and histologic grade (P = 0.013). Kaplan–Meier survival analysis revealed that high TROP2 expression correlated with poor prognosis (P = 0.046). Multivariate analysis revealed that TROP2 expression was an independent prognostic marker for overall survival of ADC patients. Moreover, TROP2 overexpression enhanced cell proliferation, migration, and invasion in the NSCLC cell line A549, whereas knockdown of TROP2 induced apoptosis and impaired proliferation, migration, and invasion in the PC-9 cells. Altogether, our data suggest that TROP2 plays an important role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease.

Breast implant capsule-associated squamous cell carcinoma: a report of 2 cases.

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Olsen, Daniel L; Keeney, Gary L; Chen, Beiyun; Visscher, Daniel W; Carter, Jodi M

2017-09-01

The use of prosthetic implants for breast augmentation has become commonplace. Although implants do not increase the risk of conventional mammary carcinoma, they are rarely associated with anaplastic large cell lymphoma. We report 2 cases of breast implant capsule-associated squamous cell carcinoma with poor clinical outcomes. Both patients (56-year-old woman and 81-year-old woman) had long-standing implants (>25 years) and presented with acute unilateral breast enlargement. In both cases, squamous cell carcinoma arose in (focally dysplastic) squamous epithelium-lined breast implant capsules and widely invaded surrounding breast parenchyma or chest wall. Neither patient had evidence of a primary mammary carcinoma or squamous cell carcinoma at any other anatomic site. Within 1 year, one patient developed extensive, treatment-refractory, locoregional soft tissue metastasis, and the second patient developed hepatic and soft tissue metastases and died of disease. There are 2 prior reported cases of implant-associated squamous cell carcinoma in the plastic surgery literature; one provides no pathologic staging or outcome information, and the second case was a capsule-confined squamous cell carcinoma. Together, all 4 cases share notable commonalities: the patients had long-standing breast implants and presented with acute unilateral breast pain and enlargement secondary to tumors arising on the posterior aspect of squamous epithelialized implant capsules. Because of both its rarity and its unusual clinical presentation, implant capsule-associated squamous cell carcinoma may be underrecognized. The aggressive behavior of the tumors in this series underscores the importance of excluding malignancy in patients with long-standing breast implants who present with acute unilateral breast pain and enlargement. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of PTP1B disrupts cell–cell adhesion and induces anoikis in breast epithelial cells

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Hilmarsdottir, Bylgja; Briem, Eirikur; Halldorsson, Skarphedinn; Kricker, Jennifer; Ingthorsson, Sævar; Gustafsdottir, Sigrun; Mælandsmo, Gunhild M; Magnusson, Magnus K; Gudjonsson, Thorarinn

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell–cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype. PMID:28492548

Mechanism of arctigenin-mediated specific cytotoxicity against human lung adenocarcinoma cell lines.

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Susanti, Siti; Iwasaki, Hironori; Inafuku, Masashi; Taira, Naoyuki; Oku, Hirosuke

2013-12-15

The lignan arctigenin (ARG) from the herb Arctium lappa L. possesses anti-cancer activity, however the mechanism of action of ARG has been found to vary among tissues and types of cancer cells. The current study aims to gain insight into the ARG mediated mechanism of action involved in inhibiting proliferation and inducing apoptosis in lung adenocarcinoma cells. This study also delineates the cancer cell specificity of ARG by comparison with its effects on various normal cell lines. ARG selectively arrested the proliferation of cancer cells at the G0/G1 phase through the down-regulation of NPAT protein expression. This down-regulation occurred via the suppression of either cyclin E/CDK2 or cyclin H/CDK7, while apoptosis was induced through the modulation of the Akt-1-related signaling pathway. Furthermore, a GSH synthase inhibitor specifically enhanced the cytotoxicity of ARG against cancer cells, suggesting that the intracellular GSH content was another factor influencing the susceptibility of cancer cells to ARG. These findings suggest that specific cytotoxicity of ARG against lung cancer cells was explained by its selective modulation of the expression of NPAT, which is involved in histone biosynthesis. The cytotoxicity of ARG appeared to be dependent on the intracellular GSH level. Copyright © 2013 Elsevier GmbH. All rights reserved.

Breast as an unusual site of metastasis- series of 3 cases and review of literature.

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Hebbar, Ashwin K; Shashidhar, K; S, Krishna Murthy; Kumar, Veerendra; Arjunan, Ravi

2014-09-01

Background and objectives Metastasis to the breast from extra mammary sites is uncommon with an incidence ranging from 1.2 to 2 % in clinical reports. Approximately 300 cases of breast metastasis from extra mammary sites have been reported, mostly in small series or as a single case report. Gastrointestinal adenocarcinoma metastasising to the breast is also very rare and only 30 cases have been reported in the literature. Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. Radiological features and immunohistochemistry especially for steroid hormone receptors (ER/PR) and expression of gross cystic disease fluid protein (GCDFP) and presence of other immunohistochemistry protein factors in breast metastasis which are specific to primary site may be helpful in differentiating these two conditions. Materials and methods In this series of 3 cases of breast as an unusual site of metastasis, we present different cases of adenocarcinoma of stomach, sigmoid colon and kidney with metastasis to the breast and discuss the differential diagnosis and management plans. Conclusion In conclusion, secondary tumors to the breast are rare and thus differentiating primary tumors from metastatic breast carcinoma is important for rational and optimum therapy and avoidance of unnecessary radical surgery. Palpable breast lump without typical radiological signs of primary breast carcinoma in patients with known primary should be suspected of representing metastasis.

Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

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Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

2009-01-01

The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

Cytotoxic Activity of Selected Iranian Traditional Medicinal Plants on Colon, Colorectal and Breast Cancer Cell Lines

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Leila Mohammad Taghizadeh Kashani

2014-11-01

Full Text Available Background: Many natural products from plants have been recognized to exert anticancer activity. In this study, ethanolic extracts of selected medicinal herbs from Iranian flora including Alyssum homolocarpum Fisch. (from seeds, Urtica dioica L. (from aerial parts, Cichorium intybus L. (from roots and Solanum nigrum L. (from fruits, were evaluated for their cytotoxic effect on different cell lines.Methods: Cytotoxic effect of these extracts was studied on three different cancer cell lines; colon carcinoma (HT-29, colorectal adenocarcinoma (Caco-2 and breast ductal carcinoma (T47D. In addition, Swiss mouse embryo fibroblasts (NIH 3T3 were used as normal nonmalignant cells. MTT assay (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide was utilized for calculating the cytotoxicity of extracts on cell lines.Results: Results showed the potent cytotoxic activity of U. dioica ethanolic extract against T47D cell line with IC50 value of 46.14±4.55 µg/ml. Other extracts showed poor activity with IC50>100 µg/ml.Conclusions: Cytotoxic activity recorded in the present study revealed high potential antiproliferative activity of U. dioica ethanolic extract against T47D cell line. The real IC50 values of this extract may be considerably lower than the IC50 measured in our study if its pharmacological active compounds become pure. The results emphasize the importance of studies on U. dioica ethanolic extract to characterize potential components as cytotoxic natural medicines.

Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells

International Nuclear Information System (INIS)

McDonald, Elizabeth S.; Mankoff, Julia; Makvandi, Mehran; Chu, Wenhua; Chu, Yunxiang; Mach, Robert H.; Zeng, Chenbo

2017-01-01

The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation. - Highlights: • PARPi, YUN3-6 and olaparib, and σ2 ligands, SV119 and SW43, were evaluated. • Mouse and human breast cancer cells, EMT6 and MDA-MB-231 respectively, were used. • YUN3-6 and SV119 synergistically triggered cell death in EMT6 cells. • Olaparib and SW43 additively triggered cell death in MDA-MB-231 cells. • Olaparib arrested cells in G2/M in MDA-MB-231 cells.

Adenocarcinoma of the Lung Acquiring Resistance to Afatinib by Transformation to Small Cell Carcinoma: A Case Report

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Jun Nishimura

2017-07-01

Full Text Available A 65-year-old woman visited our hospital due to right chest pain and dyspnea on exertion. Chest radiography revealed decreased permeability of the right lung. Computed tomography demonstrated a huge mass in the right upper lobe and right pleural effusion. Right pleural effusion cytology yielded a diagnosis of adenocarcinoma and was positive for mutation of epidermal growth factor receptor (EGFR; exon 21 L858R. Afatinib was selected for the initial treatment. Multiple tumors regressed remarkably, but then rapidly progressed 3 months later. We performed re-biopsy to detect the mechanism of resistance to afatinib. Histopathology revealed a mixture of small cell carcinoma (SCC and adenocarcinoma harboring same EGFR mutation. To the best of our knowledge, this is the first report of transformation to SCC after treatment with afatinib.

Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma.

Science.gov (United States)

Bai, Yun; Qiu, Jianxing; Shang, Xueqian; Liu, Ping; Zhang, Ying; Wang, Ying; Xiong, Yan; Li, Ting

2015-05-01

Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis.