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Sample records for human endometrial adenocarcinoma

  1. Imaging of endometrial adenocarcinoma

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    Barwick, T.D. [Department of Radiology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Rockall, A.G. [Department of Radiology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Barton, D.P. [Department of Gynaecological Oncology, Royal Marsden Hospital, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom)

    2006-07-15

    Endometrial cancer is the most common gynaecological malignancy and the incidence rising. Prognosis depends on age of patient, histological grade, depth of myometrial invasion and cervical invasion and lymph node metastases. Myometrial invasion and accurate cervical involvement cannot be predicted clinically. Pre-treatment knowledge of these criteria is advantageous in order to plan treatment. The clinical challenge is to effectively select patients at risk of relapse for more radical treatment whilst avoiding over treating low risk cases. This is important as endometrial cancer predominately occurs in postmenopausal women with co-morbidities. Modern imaging provides important tools in the accurate pre-treatment assessment of endometrial cancer and may optimize treatment planning. However, there is little consensus to date on imaging in the routine preoperative assessment of endometrial carcinoma and practice varies amongst many gynaecologists. Transvaginal ultrasound is often the initial imaging examination for women with uterine bleeding. However, once the diagnosis of endometrial cancer has been made, contrast-enhanced magnetic resonance imaging (MRI) provides the best assessment of the disease. The results of contrast-enhanced MRI may identify patients who need more aggressive therapy and referral to a cancer centre. In this article we review the role of imaging in the diagnosis and staging/preoperative assessment of endometrial carcinoma.

  2. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

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    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  3. Diagnostic criteria for distinguishing endometrial adenocarcinoma from complex atypical endometrial hyperplasia.

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    Mittal, Khush; Salem, Amira; Lo, Andy

    2014-01-01

    Morphologic criteria for distinguishing endometrial adenocarcinoma from complex atypical endometrial hyperplasia have been described previously, but they have not been examined extensively for their individual ability for predicting endometrial adenocarcinoma as determined by subsequent hysterectomy. We examined endometrial biopsies diagnosed in the spectrum of complex atypical endometrial hyperplasia to well-differentiated endometrial adenocarcinoma for various morphologic features that may be predictive for the presence of myoinvasive endometrial adenocarcinoma in subsequent hysterectomy. Cases diagnosed as FIGO grade I endometrial adenocarcinoma or complex atypical endometrial hyperplasia in endometrial biopsies seen at New York University Medical Center from 2003 to 2006 were analyzed for the presence of various morphologic features without the knowledge of hysterectomy findings. Only those cases with subsequent hysterectomy were included in the study. The data were analyzed to identify features with high specificity for a finding of myoinvasive endometrial adenocarcinoma in subsequent hysterectomy. Extreme glandular crowding (95% or greater area with glands, aggregate size 3 mm or greater) and cribriform foci of any size were found to have high sensitivity and specificity for the finding of myoinvasive carcinoma in subsequent hysterectomy (P < .0001).

  4. Maspin expression, subcellular localization and clinicopathological correlation in endometrial hyperplasia and endometrial adenocarcinoma.

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    Blandamura, Stella; Alessandrini, Lara; Saccardi, Carlo; Giacomelli, Luciano; Fabris, Alberta; Borghero, Angela; Litta, Pietro

    2014-06-01

    Maspin expression in endometrial hyperplasia and endometrial endometrioid adenocarcinomas was assessed and its correlation with p53 and Ki67 expressions and clinical outcome, as well as its potential to distinguish typical from atypical endometrial hyperplasia, were assessed in this study. Histological sections from 114 cases of endometrial endometrioid adenocarcinoma, 75 cases of endometrial hyperplasia (typical and atypical), and 23 normal endometrial tissue samples were examined. The most representative hematoxylin-eosin slides were selected and 2-3 micron-thick sections were cut for immunohistochemical staining with maspin, p53, and Ki67 antibodies. While there was no maspin expression in normal endometrial cells, it was present in 14.5% of the patients with endometrial hyperplasia without atypia. Staining for maspin was positive in atypical hyperplasia and endometrial adenocarcinoma in, respectively, 45% and 49.1% of the cases studied. No statistically significant correlations were found between maspin and Ki-67 antibodies or p53 expression. Our findings showed that maspin expression, which generally correlates with a less aggressive behavior, is significantly higher in atypical hyperplasia and in endometrial endometrioid adenocarcinoma. Maspin positivity in endometrial hyperplasia could be used to identify pseudo-atypical hyperplasia and could be considered a potentially useful prognostic parameter in those cases in which adenocarcinomas are well differentiated.

  5. Endometrial Adenocarcinoma and Mucocele of the Appendix: An Unusual Coexistence

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    Ioannis Kalogiannidis

    2013-01-01

    Full Text Available Appendiceal mucocele is a rare clinical entity, which is however quite often associated with mucinous ovarian tumor. The coexistence of mucinous cystadenoma of the appendix and endometrial adenocarcinoma has not been reported before. A 49-year-old woman presented to our clinic with postmenopausal bleeding and no other symptom. Endometrial biopsy revealed endometrial adenocarcinoma of endometrioid type (grade I. Preoperative CT scanning revealed an appendiceal mucocele, and a colonoscopy confirmed the diagnosis. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and appendectomy. The final histopathological examination showed a mucinous cystadenoma of the appendix and confirmed the diagnosis of endometrioid endometrial adenocarcinoma. The coexistence of appendiceal mucocele and female genital tract pathology is rare. However, gynecologists should keep a high level of suspicion for such possible coexistence. Both the diagnostic approach and the therapeutic management should be multidisciplinary, most importantly with the involvement of general surgeons.

  6. Oral malignant acanthosis nigricans associated with endometrial adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Han-Wen Chu; Jing-Min Li; Guan-Fu Chen; Jing-Yuan Ma

    2014-01-01

    We report a 59-year-old patient with malignant acanthosis nigricans associated with metastasis of endometrial carcinoma. The patient presented papillomatosis lesions that appeared to be benign on multiple skins of body folds, particularly on lips. The lesions in lips and axilla had histological characteristic appearances of acanthosis nigricans, while the masses in abdomen and pelvis were metastasis endometrial adenocarcinoma. The article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of doctors in screening for body internal tumors.

  7. Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

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    2013-01-23

    Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

  8. Endometrial Adenocarcinoma with Concomitant Left Atrial Myxoma

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    Lisa N. Abaid

    2009-08-01

    Full Text Available Background: Atrial myxomas are the most common primary heart tumors and predominantly considered to be benign lesions. Case Study: We report a case involving a 77-year-old woman who presented with a pelvic mass. She was found to have a primary endometrial cancer and primary lung cancer with concomitant metastatic adrenal gland and mesenteric lesions. Her prior medical history also included an untreated 4.0 × 2.0-cm left atrial myxoma which was identified on CT scan during the workup of her pelvic mass. Results: A clinical decision was made to proceed with surgery for the pelvic mass with a subsequent recommendation for left atrial mass resection. Currently, the patient is scheduled to begin chemotherapy for primary lung cancer. Conclusion: The reported incidence of uterine cancer and a concurrent atrial myxoma is very rare. Consequently, the manner and timing in which treatment should be provided is imprecise. In the present case, the risk for cardiac complications was high, but given the presence of a partial bowel obstruction and the need to diagnose the primary site of her metastatic malignancy, the decision was made to proceed with exploratory abdominal surgery.

  9. Hypoxia and prostaglandin E receptor 4 signalling pathways synergise to promote endometrial adenocarcinoma cell proliferation and tumour growth.

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    Rob D Catalano

    Full Text Available The prostaglandin endoperoxide synthase (PTGS pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG E(2. PTGS2 expression and PGE(2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE(2 regulate endometrial tumour growth is unknown. Here we investigated (a the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3 and PGE receptors (PTGER1-4 in endometrial adenocarcinomas compared with normal endometrium and (b the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE(2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE(2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells.

  10. Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

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    2014-09-09

    Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

  11. Treatment and clinical behavior of endometrial endometrioid adenocarcinoma

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    Katabuchi, Hidetaka; Suenaga, Yoshito; Okamura, Hitoshi [Kumamoto Univ. (Japan). School of Medicine

    2001-08-01

    Cases of endometrial carcinoma treated in a university hospital between 1986 and 1998 were analyzed. More specifically, cases of endometrial carcinoma treated at Kumamoto University Hospital during the past 13 years were analyzed in terms of additional treatment given as adjuvant therapy after surgery. Among the total of 175 cases of endometrial carcinoma, surgery was the primary treatment modality in 173 (98.9%) and the other 2 (1.1%) were treated by chemotherapy and/or radiotherapy without surgery. Of the 173 surgical cases, 158 (91.4%) were cases of endometrioid adenocarcinoma, and after excluding the cases of double cancer, the remaining 147 cases were included in the analysis. At Kumamoto University hospital, radical hysterectomy and pelvic lymphadenectomy have been performed in cases in which cervical invasion is indicated by hysteroscopy and/or MRI, invasion of the muscle coat of the uterus appears on MRI images, and in which carcinoma with specific histology (e.g., serous adenocarcinoma) or anaplastic endometrioid adenocarcinoma is seen. Semi-radical hysterectomy and pelvic lymphadenectomy have been considered to be indicated in all other cases. Adjuvant chemotherapy and radiotherapy after surgery has been indicated for cases in which invasion of the muscle coat of the uterus is to a depth of more than half its thickness, stromal invasion of the cervix is seen, or invasion of the serosa or metastasis to the uterine adnexae or lymph nodes is seen. Patients were externally irradiated with a dose of 50 Gy to the whole pelvis as adjuvant radiotherapy. The follow-up period ranged from 4 to 148 months. Of the 147 cases, 105 (71.4%) were treated by hysterectomy alone and the other 42 received adjuvant therapy (chemotherapy in 27 cases, radiotherapy in 15 cases). All stage Ia patients (16 cases) survived, and none were given additional therapy. Only 4.8% of the stage Ib cases (62) and 7.1% of the stage IIa cases (14) received adjuvant therapy, and no recurrences

  12. Comparative evaluation of cisplatin and carboplatin sensitivity in endometrial adenocarcinoma cell lines.

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    Rantanen, V; Grénman, S.; Kulmala, J; Grénman, R

    1994-01-01

    Platinum analogues are frequently used in the treatment of advanced or recurrent endometrial cancer. To study the sensitivity of endometrial cancer to cisplatin and carboplatin, we tested two long-established (RL95-2, KLE) and six new cell lines (UM-EC-1, UM-EC-2, UM-EC-3, UT-EC-2A, UT-EC-2B, UT-EC-3) using the 96-well-plate clonogenic assay. This assay has proven to be suitable for testing chemosensitivity of both adenocarcinoma and squamous cell carcinoma. The chemosensitivity was expressed...

  13. Adenocarcinoma involving the uterine cervix: magnetic resonance imaging findings in tumours of endometrial, compared with cervical, origin

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    Haider, M.A. [Univ. of Toronto, Dept. of Medical Imaging, Univ. Health Network, Mount Sinai Hospital, Toronto, Ontario (Canada)]. E-mail: mhaider@utoronto.ca; Patlas, M. [McMaster Univ., Dept. of Radiology, Hamilton General Hospital, Hamilton, Ontario (Canada); Jhaveri, K. [Univ. of Toronto, Dept. of Medical Imaging, Univ. Health Network, Mount Sinai Hospital, Toronto, Ontario (Canada); Chapman, W. [Univ. of Toronto, Dept. of Pathology, Univ. of Health Network, Toronto, Ontario (Canada); Fyles, A. [Univ. of Toronto, Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. Health Network, Toronto, Ontario (Canada); Rosen, B. [Univ. of Toronto, Dept. of Obstetrics and Gynecology, Univ. Health Network, Toronto, Ontario (Canada)

    2006-02-15

    To determine the distinctive magnetic resonance imaging (MRI) features of cervical and endometrial adenocarcinoma that present clinically as cervical mass. From 1999 to 2002, 56 patients with adenocarcinoma on the initial biopsy of a cervical mass underwent MRI at our institution. Of these, 42 had a visible mass on MRI. Pathology review of all available tissue was the reference standard. A site of origin was determined by the pathologist in 38 of the 42 patients, and these were the cases evaluated; of these patients, 32 cases had adenocarcinoma and 6 had adenosquamous cancers. Findings were significantly more prevalent in patients with adenocarcinomas of endometrial, compared with cervical, origin for endometrial thickening (11 [73%] and 3 [13%], respectively; P = 0.0003), endometrial mass (11 [73%] and 1 [4%], respectively; P < 0.0001), endometrial cavity expansion by a mass (9 [60%] and 2 [9%], respectively; P = 0.001), and invasion of myometrium from endometrium (9 [60%] and 0, respectively; P < 0.0001). Adenocarcinomas of the endometrium that involve the cervix have MRI features that help distinguish them from primary adenocarcinomas of the cervix. (author)

  14. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

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    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

  15. Pathologic fracture of the femur due to endometrial adenocarcinoma metastasis in a female pet rabbit (Oryctolagus cuniculi).

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    Haist, Verena; Hirschfeld, Simon Gonzales; Mallig, Carolin; Fehr, Michael; Baumgärtner, Wolfgang

    2010-01-01

    This case report describes the clinical, pathomorphological and histopathological findings in a 12-year-old female pet rabbit with a pathologic fracture of the femur due to a metastasising endometrial adenocarcinoma. The animal was presented due to a history of right hindlimb lameness and inappetence. A fracture of the right femur with adjacent lyric bone lesions was detected by clinical and X-ray examination. Necropsy and histopathology revealed an endometrial adenocarcinoma with metastasis to the right femoral bone, resulting in the pathologic fracture. In both locations, tumour cells were immunohistochemically positive for pan-cytokeratin. Additionally, the animal suffered from an Encephalitozoon cuniculi infection which manifested itself in a multifocal granulomatous encephalitis and bilateral chronic inflammatory lesions in the kidneys.The report shows that in case of bone fractures in female pet rabbits the possibility of a pathologic fracture due to metastasising endometrial adenocarcinoma has to be considered.

  16. Predicting the coexistence of an endometrial adenocarcinoma in the presence of atypical complex hyperplasia: immunohistochemical analysis of endometrial samples

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    Robbe, E.J.; Kuijk, S.M. van; Boed, E.M. de; Smits, L.J.; Wurff, A.A. van der; Kruitwagen, R.F.P.M.; Pijnenborg, J.M.A.

    2012-01-01

    OBJECTIVE: This study aimed to determine whether immunohistochemical markers in complex atypical endometrial hyperplasia could predict the presence of a concurrent endometrial carcinoma. METHODS: Endometrial biopsies of 39 patients with complex atypical hyperplasia were selected retrospectively betw

  17. Relative binding affinity does not predict biological response to xenoestrogens in rat endometrial adenocarcinoma cells.

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    Strunck, E; Stemmann, N; Hopert, A; Wünsche, W; Frank, K; Vollmer, G

    2000-10-01

    The possible adverse effects of the so-called environmental estrogens have raised considerable concern. Developmental, endocrine and reproductive disorders in wildlife animals have been linked to high exposure to persistent environmental chemicals with estrogen-like activity (xenoestrogens); yet, the potential impact of environmental estrogens on human health is currently under debate also due to lack of data. A battery of in vitro assays exist for identifying compounds with estrogenic activity, but only a few models are available to assess estrogenic potency in a multiparametric analysis. We have recently established the endometrial adenocarcinoma cell line RUCA-I; it enables us to compare estrogenic effects both in vitro and in vivo as these cells are estrogen responsive in vitro and grow estrogen sensitive tumors if inoculated in syngeneic animals in vivo. Here we report in vitro data concerning (a) the relative binding affinity of the selected synthetic chemicals Bisphenol A, nonylphenol, p-tert-octylphenol, and o,p-DDT to the estrogen receptor of RUCA-I cells and (b) the relative potency of these compounds in inducing increased production of complement C3, an endogenous estrogen-responsive gene. Competitive Scatchard analysis revealed that xenoestrogens bound with an at least 1000-fold lower affinity to the estrogen receptor of RUCA-I cells than estradiol itself, thereby exhibiting the following affinity ranking, estradiol>nonylphenol>bisphenol A approximately p-tert-octylphenol>o,p-DDT. Despite these low binding affinities, bisphenol A, nonylphenol and p-tert-octylphenol increased production of complement C3 in a dose dependent manner. Compared with estradiol, only 100-fold higher concentrations were needed for all the compounds to achieve similar levels of induction, except o,p-DDT which was by far less potent. Northern blot analyses demonstrated that the increased production of complement C3 was mediated by an increased transcription. In summary, cultured

  18. The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma.

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    Smith, H O; Anderson, P S; Kuo, D Y; Goldberg, G L; DeVictoria, C L; Boocock, C A; Jones, J G; Runowicz, C D; Stanley, E R; Pollard, J W

    1995-03-01

    Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the

  19. Prevalence of Human Papillomavirus in endometrial cancer

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    Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen

    2014-01-01

    HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....

  20. Translational Study on Correlation Between Disturbance of Estrogen and Lipid Metabolism and Occurrence and Progression of Endometrial Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    YU Cui-ge; HUANG Jian-feng; JIANG Xiang-yang

    2016-01-01

    Objective: To explore the correlation between disturbance of estrogen and lipid metabolism and occurrence and progression of endometrial adenocarcinoma so as to seek the early-warning markers for endometrial adenocarcinoma. Methods:Seventy-nine patients initially diagnosed as endometrial adenocarcinoma were collected as research group, and 70 healthy people with normal endometrium at the same term were as control group. The levels of fasting blood glucose (FBG), serum total triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), estradiol (E2), progesterone (P), testosterone (T) and fasting insulin (FINS) were all detected in two groups, and the risk factors of endometrial carcinoma were analyzed by non-conditional Logistic regression model. Results: The age, body mass index (BMI), FINS and homeostasis model assessment for insulin resistance (HOMA-IR) in research group were all higher than those in control group dramatically (P=0.0000). The level of HDL-C was signiifcantly lower, while that of E2 was markedly higher in premenopausal patients in research group than in control group, and there was statistical significance (P=0.0000). The levels of TC, TG, LDL-C, E2 and T in menopausal patients were all higher, while that of HDL-C was lower in research group than in control group, and all the differences were statistically signiifcant (P<0.05). The risk factors of endometrial adenocarcinoma included increase of BMI, E2, TG, and FIN as well as presence of HOMA-IR (OR=6.535,P=0.010; OR=7.796,P=0.011; OR=4.371,P=0.006; OR=6.392,P=0.020; OR=3.711, P=0.021). Conclusion:Women with increase of BMI, E2, TG, and FIN as well as presence of HOMA-IR can be considered as a high-risk population for developing endometrial adenocarcinoma.

  1. Risk factor analysis of recurrence in low-grade endometrial adenocarcinoma.

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    Roma, Andres A; Rybicki, Lisa A; Barbuto, Denise; Euscher, Elizabeth; Djordjevic, Bojana; Frauenhoffer, Elizabeth; Kim, Insun; Hong, Sung Ran; Montiel, Delia; Ali-Fehmi, Rouba; Malpica, Anais; Silva, Elvio G

    2015-10-01

    Prognosis of endometrial adenocarcinoma is favorable; however, the risk of recurrence ranges from 7% to 13%. Recurrence has been related to age, tumor type, International Federation of Gynecology and Obstetrics grade, depth of invasion, and lymphovascular invasion (LVI); however, morphologic features that would predict the site of recurrence have not been established. In this multi-institutional study, we reviewed 589 patients with International Federation of Gynecology and Obstetrics grades 1 or 2 endometrial adenocarcinoma, endometrioid type. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors for recurrence and survival. Univariate analysis revealed features of tumors that recurred only in the vagina: low nuclear grade; superficial myoinvasion; minimal to no LVI; and minimal myoinvasion with microcystic, elongated, and fragmented (MELF) pattern; low nuclear grade and superficial myoinvasion persisted on multivariate analysis. Features of tumors that recurred at other sites included large size, deep myoinvasion, tumor necrosis, 1 or more LVI foci, LVI foci distant/deeper than invasive tumor front, MELF myoinvasion pattern, lower uterine segment and cervical stromal involvement, pelvic and/or paraaortic lymph node metastases at presentation, and higher grade of tumor in the metastatic foci, whereas increased percentage of solid component and lower percentage of mucinous features were marginally associated. Tumors with recurrences only in vagina had different features than tumors that recurred at other sites. The presence of tumor necrosis, MELF foci at the invasive tumor front, and the percentage of solid component and mucinous features could be helpful in grading endometrioid adenocarcinomas, if a 2-tier rather than a 3-tier grading system is accepted in the future.

  2. Outcome of conservative treatment and subsequent assisted reproductive technology for patients with early-stage endometrial adenocarcinoma and poor fertility potential

    Institute of Scientific and Technical Information of China (English)

    TONG Xiao-mei; ZHU Hai-yan; LIN Xiao-na; JIANG Ling-ying; XU Wei-hai; LIU Liu; ZHANG Song-ying

    2012-01-01

    Conservative treatment with high doses of progestin is an alternative to standard hysterectomy for young patients with early-stage endometrial adenocarcinoma who desire to preserve their fertility.Here we report a patient with well-differentiated early-stage endometrial adenocarcinoma and poor fertility potential who failed to become pregnant in two in vitro fertilization-embryo transfer cycles and suffered a relapse after conservative treatment.This case illustrates that assessment of fertility potential is critical at the time of initial evaluation and conservative treatment planning for patients with endometrial adenocarcinoma.Chin Med J 2012; 125(19):3578-3580

  3. Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; vaginal versus other sites.

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    Moschiano, Elizabeth J; Barbuto, Denise A; Walsh, Christine; Singh, Kanwaljit; Euscher, Elizabeth D; Roma, Andres A; Ali-Fehmi, Rouba; Frauenhoffer, Elizabeth E; Montiel, Delia P; Kim, Insun; Djordjevic, Bojana; Malpica, Anais; Hong, Sung Ran; Silva, Elvio G

    2014-05-01

    Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

  4. Anticancer Effect of 5-Florouracil Combined with Extract of Rosa roxburghii Tratt on Human Endometrial Adenocarcinoma%刺梨提取物联合5-氟尿嘧啶抗人子宫内膜腺癌作用

    Institute of Scientific and Technical Information of China (English)

    戴支凯; 杨小生; 余丽梅

    2011-01-01

    Objective To investigate anticancer effects of 5-florouracil (5-FU) combined with CL, extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma cell line (JEC). Methods JEC cells cultured in vitro in the logarithmic growth phase were seeded in the culture plate and divided into the control group (RPMI 1640), the positive group (10~4 mol/L 5-FU), the CL groups (at the dose of 0.01, 0.1, 1, 10, and 100 ug/mL), and the CL (0. 01, 0.1, 1, 10, and 100 ug/mL) combined with 5-FU groups. Effects of 5-FU combined with CL on JEC cell growth were drawn and measured by MTT and growth curves. Effects of CL combined with 5-FU on the JEC cell differentiation was analyzed by detecting the reduction capability of nitrobenzene thiocyanate (NBT) and lactate dehydrogenase (LDH) contents in the cultured medium. Effects of CL combined with 5-FU on the JEC cell apoptosis and cell proliferation cycle were detected by acridine orange (AO)/ethidium bromide (EB) fluorescent staining and flow cytometry (FCM). Results The proliferation inhibitory effect of CL combined with 5-FU on JEC cells was enhanced when compared with that of CL or 5-FU alone (P<0.05). The percentages of NBT positive JEC cells and apoptotic JEC cells increased in the 5-FU combined with CL groups when compared with 5-FU group or the CL group alone (P<0.05). The LDH concentration of the JEC cell culture supemate decreased in 5-FU combined with CL groups (P<0.05). Furthermore, the percentage of G0-G1 phase JEC cells treated by 5-FU combined with CL was higher than that of 5-FU or CL alone (P <0.05). Conclusion CL could enhance anticancer effects of 5-FU. Its mechanisms might be correlated with reinforcing the cytotoxicity of 5-FU, inducing cell differentiation and apoptosis, and inhibiting cell proliferation and division.%目的 探讨刺梨提取物(CL)联合5-氟尿嘧啶(5-florouracil,5-FU)的抗子宫内膜腺癌细胞株(JEC)作用.方法 将体外培养的指数生长期细胞接种于培

  5. Synchronous Ovarian and Endometrial Endometrioid Adenocarcinoma Presenting with Nonbacterial Thrombotic Endocarditis and Pulmonary Thromboembolism: Adenocarcinoma with Thrombotic Events

    Directory of Open Access Journals (Sweden)

    N. K. Erturk

    2015-01-01

    Full Text Available Introduction. Nonbacterial thrombotic endocarditis (NBTE is a rare manifestation of hypercoagulability in patients with malignant neoplasms. Case Report. A fifty-six-year-old woman presented to the emergency service; the clinical workup revealed deep vein thrombosis in right leg and bilateral massive PTE. As the abdominal sections on the spiral CT revealed a giant pelvic mass of ovarian origin, she was referred to our hospital’s gynecologic oncology department. She was scheduled for surgery under enoxaparin. She described numbness on one side of her face. Cranial imaging findings revealed acute ischemic cerebral lesions and transesophageal echocardiogram showed vegetation on the aortic cusp. Under anticoagulation treatment, she underwent hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy. After tumor resection, her neurological symptoms dissolved with aggressive anticoagulant treatment. Pathology result was synchronous endometrial and ovarian adenocarcinoma. Discussion. NBTE is a rare condition often associated with advanced malignancies. Peripheral embolism and venous thrombosis are complications that have been associated with NBTE due to hypercoagulable state. These disorders could be resistant to routine anticoagulant treatment. In case of a thrombotic complication due to ovarian malignancy, surgical resection of the primary tumor may increase the effect of anticoagulant treatment.

  6. Circulating microRNAs as a fingerprint for endometrial endometrioid adenocarcinoma.

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    Lin Wang

    Full Text Available BACKGROUND: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and endometrial endometrioid adenocarcinoma (EEC is the major histological type of endometrial cancer. There is a great need for better markers with high sensitivity and specificity to permit early diagnosis and proper management of EEC. The aim of our study is to identify a miRNA classifier within plasma as a noninvasive biomarker for EEC diagnosis. METHODS: This study was a retrospective case-control analysis which contained two independent cohorts including 93 participants. First, we screened 375 miRNAs in 29 plasma samples. 9 of the miRNAs were selected to be evaluated their expression by quantitative reverse-transcriptase polymerase chain reaction. A stepwise logistic regression model was then used to establish a new classifier in the validation cohort. Area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy. Co-expression analysis was used to verify the independence of results. RESULTS: miR-15b, -27a, and -223 were found to be differentially expressed in the EEC plasma between the two cohorts and had few connections with other miRNAs. The areas under the curve (AUC were 0.768, 0.813, and 0.768 for miR-15b, -27a, and 223, respectively. miR-27a and CA125 can be combined as a potential non-invasive biomarker for detecting EEC, with the AUC of 0.894. CONCLUSION: Our study demonstrated three miRNAs, including miR-15b, -27a, and -233 have a good clinical value in EEC diagnosis. The classifier, including miR-27a and CA125, demonstrated a high accuracy in the diagnosis of EEC and might serve as a novel non-invasive biomarker in the future.

  7. Efficacy of megestrol acetate in treatment of 21 young patients with endometrial adenocarcinoma

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    Eftekhar Z

    2007-05-01

    Full Text Available Background: Endometrial cancer is the most common malignancy of genital system which is commonly seen after menopause. Rises in the age of marriage non-surgical methods, using systemic progestins, have been evaluated to treat the young patients with well-differentiated endometrial cancer who wish to preserve their fertility. Methods: Twenty one infertile patients with stage Ia well-differentiated endometrial adenocarcinoma were enrolled in a quasi-experimental study. The treatment initiated with 160mg/d of megestrol acetate then continued with 320mg/d for non-responsive cases. Patients follow up with FD&C and hysteroscopy. Patients divided in two groups on the basis of response to therapy and persistent. The responsive patients were introduced to IVF group and evaluated for later fertility and birth of alive newborns for three years. Results: This study showed a response rate of 85.71% and 14.29% undergoing TAH. The mean duration of treatment was 5.85±2.00 month. The response to therapy was observed in 27.78% with dose of 160mg/d and the remaining patients with 320mg/d. Pregnancy occurred in 27.78%, 2 of which ended up in a term delivery and the others ended before term. Recurrence happened in 16.67% that 66.67% of them experienced remission again. Conclusion: Use of 320mg/d seems to be associated with a better therapeutic response. Serious complications were not observed with this dose. Furthermore, continuance of the drug for three month following a normal pathology report was decreased the rate of recurrence.

  8. Histologic effects of medroxyprogesterone acetate on endometrioid endometrial adenocarcinoma: a Gynecologic Oncology Group study.

    Science.gov (United States)

    Zaino, Richard J; Brady, William E; Todd, William; Leslie, Kimberly; Fischer, Edgar G; Horowitz, Neil S; Mannel, Robert S; Walker, Joan L; Ivanovic, Marina; Duska, Linda R

    2014-11-01

    Progestins have been used in the treatment of recurrent endometrial adenocarcinoma for almost 50 yr. Some endometrial carcinomas respond to hormonal therapy, but the mechanism of action remains incompletely known. We wished to determine the efficacy of progestins to induce a histologic response in endometrioid carcinomas and explore its effects on histologic and immunohistochemical measures of growth and cell death. The Gynecologic Oncology Group initiated a study of 75 women with endometrioid endometrial adenocarcinoma, 59 of whom received the progestin, medroxyprogesterone acetate for 21 to 24 d immediately before hysterectomy and had available slides. Initial biopsies and hysterectomies were hematoxylin and eosin-stained and immunostained for estrogen receptor (ER) and progesterone receptor (PR), progesterone receptor-β (PRB), Bcl-2, Ki-67, and cleaved caspase-3 (Casp3). A histologic response was defined subjectively, following which specific histologic measurements and semiquantitative scores of immunohistologic variables of initial biopsies were compared with posttreatment slides. Only 1 complete histologic response was seen, but 37 tumors (63%) had a partial histologic response. Specific histologic changes included the following: a decrease in the nuclear grade, the number of mitotic figures, nucleoli, and mean gland cellularity, and acquisition of more abundant eosinophilic cytoplasm, squamous metaplasia, and secretion. The tumors that displayed a subjectively defined histologic response following treatment differed initially from those that did not only with respect to initial nuclear grade and the mitotic index. Statistically significant differences in the specific histologic features in carcinomas of responders versus nonresponders following treatment were found only with respect to acquisition of pale eosinophilic cytoplasm and luminal secretion. More than 90% of tumors were initially ER positive and 76% were PR positive. The initial presence of ER or

  9. Food intake and the risk of endometrial endometrioid adenocarcinoma in Japanese women.

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    Takayama, Shin; Monma, Yasutake; Tsubota-Utsugi, Megumi; Nagase, Satoru; Tsubono, Yoshitaka; Numata, Takehiro; Toyoshima, Masafumi; Utsunomiya, Hiroki; Sugawara, Junichi; Yaegashi, Nobuo

    2013-01-01

    The present study examined the association between food intake and endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control study in Japanese women. One hundred sixty-one cases and 380 controls who completed a questionnaire regarding demographic, lifestyle, and food frequency questionnaire were analyzed. Odds ratio (OR) between selected food intakes and EEA were calculated by logistic regression analysis. After adjustment putative confounding factors, the higher intakes of vegetables [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.26-0.83], peanuts (OR = 0.48, CI = 0.27-0.86), fish (OR = 0.52, CI = 0.29-0.93), boiled egg (OR = 0.24, CI = 0.33-0.92), instant noodles (OR = 1.94, CI = 1.12-3.34), instant food items (OR = 2.21, CI = 1.31-3.74), and deep-fried foods (OR = 2.87, CI = 1.58-5.21) were associated with a risk for EEA. The inverse association with a risk of EEA was also seen in higher intakes (g/1000 kcal) for vegetables (0.45, CI = 0.25-0.81) and fish (0.53, CI = 0.30-0.94) as compare to lower intake. Higher intake of vegetables, peanuts, fish, and boiled egg was associated with a reduced risk for EEA, whereas instant noodles, instant food items, and deep-fried foods was associated with an increased risk for EAA as compared to lower levels of intake.

  10. Endometrioid adenocarcinoma associated with endometrial stromal sarcoma: A rare, often unrecognized collision tumor

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    Grace Kim

    2015-08-01

    Full Text Available We are reporting 3 cases of the uterine corpus with collision of endometrioid adenocarcinoma (EAC with endometrial stromal sarcoma (ESS. The patients' ages ranged from 36 to 59 years old. The major clinical presentation was abnormal uterine bleeding. Microscopically, all 3 cases presented with 2 separate components, EAC Grade 1 and ESS (one low grade and two high grades. The EAC component ranged from 10% to 70%, and the ESS component ranged from 30% to 70% of total tumor volume. The EAC component was stage 1A in two cases and stage II in one case. The ESS component was stages IA, IIB, and IIIB. Adjuvant hormonal therapy was administrated to one patient while a second patient was treated with chemo/radiation therapy. Two patients were still alive with no evidence of disease at 4 years post-therapy. One patient was lost for follow-up. Collision tumor should be distinguished from carcinosarcoma due to its different treatment modality, outcome and, prognosis.

  11. Giant Cavernous Hepatic Hemangioma Diagnosed Incidentally in a Perimenopausal Obese Female with Endometrial Adenocarcinoma: A Case Report.

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    Bara, Tivadar; Gurzu, Simona; Jung, Ioan; Muresan, Mircea; Szederjesi, Janos; Bara, Tivadar

    2016-02-01

    Hemangiomas are the most common benign tumors of the liver, considered giant when they exceed 50-100 mm in diameter. In the present report, we present a case of a 5.2-kg hemangioma of the right hepatic lobe, with hemangiomatous foci in the left lobe, which was incidentally diagnosed in a 53-year-old obese female hospitalized for uterine bleeding. The computed tomographic scan and physical examination revealed a giant abdominal tumor and hepatic hemangioma of the right hepatic lobe was suspected. Right hepatectomy and total hysterectomy with bilateral ovariectomy was performed. The histological examination of the surgical specimens confirmed the extremely giant cavernous hepatic hemangioma, and a synchronous pT1a endometrioid endometrial adenocarcinoma was also diagnosed. The patient remains alive without postoperative disorders, 6 months after surgery. To our knowledge, this is the first reported case of such huge hemangioma incidentally diagnosed in an obese female, with a synchronous endometrial adenocarcinoma of the uterus. Because obesity may cause hyperestrogenism, it might both increase the growth rate of hemangioma and the genesis of endometrial cancer in perimenopausal females. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Expression of retinoic acid receptors in human endometrial carcinoma.

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    Tanabe, Kojiro; Utsunomiya, Hiroki; Tamura, Mitsutoshi; Niikura, Hitoshi; Takano, Tadao; Yoshinaga, Kohsuke; Nagase, Satoru; Suzuki, Takashi; Ito, Kiyoshi; Matsumoto, Mitsuyo; Hayashi, Shin-ichi; Yaegashi, Nobuo

    2008-02-01

    The retinoids (vitamin A and its biologically active derivatives) are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) beta is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RAR beta could act as a tumor suppressor. However, the status of RAR beta in human endometrial carcinoma has not been examined. In the present study, we initially studied the effects of retinoic acid on cell proliferation and the expression of RAR alpha, RAR beta, and RAR gamma using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RAR in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally, we correlated these findings with the clinicopathological parameters. In vitro, cell growth was inhibited and RAR beta and RAR gamma mRNA was significantly induced by AM580, compared with vehicle controls, whereas RAR alpha mRNA was significantly attenuated by AM580, compared with vehicle. RAR beta was detected predominantly in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. The results of our study demonstrate that AM580 inhibits cell growth and induces RAR beta mRNA expression in the Ishikawa cell line, and the expression level of RAR beta in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma.

  13. Targeting topoisomerase IIa in endometrial adenocarcinoma: a combined chromogenic in situ hybridization and immunohistochemistry study based on tissue microarrays.

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    Tsiambas, E; Alexopoulou, D; Lambropoulou, S; Gerontopoulos, K; Karakitsos, P; Karameris, A

    2006-01-01

    Topoisomerase IIa is a nucleic enzyme that affects the topological structure of DNA and also is a target for chemotherapy (ie, anthracyclines). In this study, we coevaluated its protein expression with chromosome 17 and gene status. Using tissue microarrays, 40 cases of sporadic, primary endometrial adenocarcinomas, 5 cases of atypical hyperplasia, and 5 cases of benign hyperplasia were obtained and reembedded into two paraffin blocks with a core diameter of 1 mm. Immunohistochemistry combined with chromogenic in situ hybridization was performed in 2 and 5 microm sections, respectively. Finally using a semiautomated Image Analysis System, we evaluated the levels of Nuclear labeling index of topoisomerase IIa expression. Statistical analysis was performed by SPSS version 11.0 software. The results indicate that chromosome 17 instability (aneuploidy in 7/40 cases) and Topo IIa gene deregulation (amplification in 3/40 and deletion in 1/40 cases) are significant genetic events correlated with biologic behavior in endometrial adenocarcinoma. Because protein overexpression was observed in a significant proportion of the tumors (18/40), detection of the specific gene deregulation mechanism is a crucial process for application of targeted chemotherapies, which are characterized by different levels of cardiotoxicity and other serious effects.

  14. Determination of Heavy Metal Concentrations in Normal and Pathological Human Endometrial Biopsies and In Vitro Regulation of Gene Expression by Metals in the Ishikawa and Hec-1b Endometrial Cell Line.

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    Erwan Guyot

    Full Text Available It is well known that several metals, such as lead, mercury, cadmium, and vanadium, can mimic the effects of estrogens (metallo-estrogens. Nevertheless, there are only a few studies that have assessed the effects of toxic metals on the female genital tract and, in particular, endometrial tissue. In this context, we measured the concentrations of several trace elements in human endometrial tissue samples from individuals with hyperplasia or adenocarcinoma and in normal tissues. Hyperplasic endometrial tissue has a 4-fold higher concentration of mercury than normal tissue. Mercury can affect both the AhR and ROS signaling pathways. Thus, we investigated the possible toxic effects of mercury by in vitro studies. We found that mercury increases oxidative stress (increased HO1 and NQO1 mRNA levels and alters the cytoskeleton in the human endometrial Ishikawa cell line and to a lesser extent, in the "less-differentiated" human endometrial Hec-1b cells. The results might help to explain a potential link between this metal and the occurrence of endometrial hyperplasia.

  15. Determination of Heavy Metal Concentrations in Normal and Pathological Human Endometrial Biopsies and In Vitro Regulation of Gene Expression by Metals in the Ishikawa and Hec-1b Endometrial Cell Line

    Science.gov (United States)

    Tomkiewicz, Céline; Leblanc, Alix; Pierre, Stéphane; El Balkhi, Souleiman; Le Frère-Belda, Marie-Aude; Lecuru, Fabrice; Poupon, Joël; Barouki, Robert; Aggerbeck, Martine; Coumoul, Xavier

    2015-01-01

    It is well known that several metals, such as lead, mercury, cadmium, and vanadium, can mimic the effects of estrogens (metallo-estrogens). Nevertheless, there are only a few studies that have assessed the effects of toxic metals on the female genital tract and, in particular, endometrial tissue. In this context, we measured the concentrations of several trace elements in human endometrial tissue samples from individuals with hyperplasia or adenocarcinoma and in normal tissues. Hyperplasic endometrial tissue has a 4-fold higher concentration of mercury than normal tissue. Mercury can affect both the AhR and ROS signaling pathways. Thus, we investigated the possible toxic effects of mercury by in vitro studies. We found that mercury increases oxidative stress (increased HO1 and NQO1 mRNA levels) and alters the cytoskeleton in the human endometrial Ishikawa cell line and to a lesser extent, in the “less-differentiated” human endometrial Hec-1b cells. The results might help to explain a potential link between this metal and the occurrence of endometrial hyperplasia. PMID:26600472

  16. Clinicopathological Features Analysis of 86 Endometrial Endometrioid Adenocarcinoma Patients with Adnexal Involvement.

    Science.gov (United States)

    Zuo, Jing; Cheng, Min; Song, Yan; Li, Zhuo; Zhang, Rong; Li, Bin; Wu, Lingying

    2017-06-20

    To investigate the clinicopathological features of endometrial endometrioid adenocarcinoma(EEA)with adnexal involvement.Methods The clinicopathological data of 86 EEA patients who underwent surgical treatment at our center from January 2000 to December 2015 were analyzed retrospectively.The clinicopathological features were compared between patients with occult adnexal involvement and those with gross adnexal involvement.Results A total of 86 EEA patients with adnexal involvement(mean age:58.1 years)were included in this study,accounting for 5.4%(86/1592)of the EEA patients during the same period.Among these 86 patients,there were 13 premenopausal patients(15.1%)including 2 premenopausal patients aged under 40 years.Gross adnexal involvement was found in 47 patients(54.7%),while occult adnexal involvement was found in 39 patients(45.3%)in pathology evaluation.Ovarian metastasis was found in 34 patients(39.5%),followed by both ovarian and tubal metastasis in 19 patients(22.1%)and tubal metastasis in 33 patients(38.4%).The expressionss of estrogen receptor(χ(2)=8.086,P=0.042)and progesterone receptor(PR)(χ(2)=9.149,P=0.026)were significantly different between gross adnexal involvement group and occult adnexal involvement group,whereas no significant difference was found in other clinicopathological features(all P>0.05).The non-conditional Logistic regression analysis showed that,compared with PR no-expression group,the rate of occult microscopic adnexal involvement in PR low-expression group was 6.375 times of that of the gross adnexal involvement(P=0.005,95%CI:1.768-22.976),and the rate of occult microscopic adnexal involvement in the PR high-expression group was 3.719 times of that of gross adnexal involvement(P=0.048,95%CI:1.009-13.702). Conclusion PR expression level is remarkably lower in EEA patients with gross adnexal involvement than those with occult adenxal involvement.

  17. An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

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    Yang, Chieh-Hsiang; Almomen, Aliyah; Wee, Yin Shen; Jarboe, Elke A; Peterson, C Matthew; Janát-Amsbury, Margit M

    2015-07-01

    Endometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone-induced EH mouse model was developed using a subcutaneous estradiol (E2)-sustained releasing pellet, which elevates the serum E2 level in mice, closely mimicking the effect known as estrogen dominance with underlying, pathological E2 levels in patients. The onset and progression of EH generated within this model recapitulate a clinically relevant, pathological transformation, beginning with disordered proliferation developing to simple EH, advancing to atypical EH, and then progressing to precancerous stages, all following a chronologic manner. Although a general increase in nuclear progesterone receptor (PR) expression occurred after E2 expression, a total loss in PR was noted in some endometrial glands as disease advanced to simple EH. Furthermore, estrogen receptor (ER) expression in the nucleus of endometrial cells was reduced in disordered proliferation and increased when EH progressed to atypical EH and precancerous stages. This EH model also resembles other pathological patterns found in human disease such as leukocytic infiltration, genetic aberrations in β-catenin, and joint phosphatase and tensin homolog/paired box gene 2 (PTEN/PAX2) silencing. In summary, this new and comprehensively characterized EH model is cost-effective, easily reproducible, and may serve as a tool for preclinical testing of therapeutic agents and facilitate further investigation of EH.

  18. Phase 2 trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma.

    Science.gov (United States)

    Ramondetta, Lois M; Johnson, Alaina J; Sun, Charlotte C; Atkinson, Neely; Smith, Judith A; Jung, Maria S; Broaddus, Russel; Iyer, Revathy B; Burke, Thomas

    2009-05-01

    : The objective of this study was to determine the efficacy of mifepristone (RU-486) in women with advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma (LGESS). : Mifepristone (RU-486; 200 mg orally) was given daily to patients with progesterone receptor-positive advanced or recurrent endometrioid adenocarcinoma or LGESS. Patients were evaluated every 4 weeks for toxicity and response. Quality-of-life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy. : Twelve of 13 enrolled patients were evaluable in the first phase of accrual. Stable disease was noted in 3 of 12 patients (at 8 weeks, 12 weeks, and > or =77 weeks, respectively), and the median time to disease progression was 48 days. Among the patients who had stable disease, 2 women had endometrioid endometrial cancer, and 1 woman had LGESS. No partial or complete responses were observed. The most frequent grade 1 and 2 toxicities were anorexia, fatigue, and mood alterations observed in 50%, 50%, and 58% of patients, respectively. The most common grade 3 toxicities were fatigue and dyspnea observed in 25% and 17% of patients, respectively. One patient experienced grade 4 dyspnea. Thirty-three percent of patients had asymptomatic elevations of corticotropin. No serious treatment-related adverse events occurred. There were no significant changes in quality of life. : Single-agent mifepristone used in the treatment of recurrent endometrioid adenocarcinoma or LGESS resulted in a stable disease rate of 25%. One patient who had a biopsy-positive disease recurrence remained stable at 77 weeks. Although mifepristone was tolerated well, as a single agent, it provided limited response as a single agent in women with progesterone receptor-positive uterine tumors. Recently, was been recognized that biologic agents used as single agents may result only in stable disease unless they are combined with cytotoxic agents. The authors

  19. Cytological Study of Grade 3 Endometrioid Adenocarcinoma of Endometrial Origin: Cytoarchitecture and Features of Cell Clusters Assessed With Endometrial Brushing Cytology--Focusing on a comparison with endometrioid adenocarcinoma Grade 1, 2.

    Science.gov (United States)

    Matsui, Naruaki; Kajiwara, Hiroshi; Morishita, Akihiro; Tsukada, Hitomi; Nakazawa, Kazumi; Miyazawa, Masaki; Mikami, Mikio; Nakamura, Naoya; Sato, Shinkichi

    2015-06-20

    Aim of study was to clarify the cytological characteristics of grade 3 endometrioid adenocarcinoma of endometrial origin (G3 EA) by endometrial brushing cytology. The subjects were 11 patients in whom G3 EA was diagnosed by review of preoperative cytological specimens obtained at our hospital and related institutions between 2000 and 2010. These patients were investigated with respect to the preoperative cytological diagnosis, background changes, cell cluster patterns, and individual cellular findings. Background changes were classified as inflammatory or tumorous, while cell clusters were classified as overlapping cell cluster, sheet-like cell cluster, clump of high dense gland, papillary, or other cell cluster. Cellular findings were investigated by comparing the incidence of squamous and clear cell metaplasia, the nuclear rounding rate, and the nuclear area with the findings in a control group (35 patients with G1-2 EA). Background changes were classified as inflammatory in 63.6% and necrotic in 36.4%. The cell clusters were classified as overlapping cell cluster in 44.8%, cell cluster in 21.7%, clump of high dense gland in 10.0%, papillary in 4.0%, and other cell cluster in 19.5%. The incidence of squamous and clear cell metaplasia was 27.2% and 18.1%, respectively. The mean nuclear rounding rate was 0.97, and the mean nuclear area was 55.98 µm2. Investigation of the cytoarchitecture of G3 EA with endometrial brushing cytology revealed overlapping cell cluster and tumor cells of a relatively uniform size. These findings suggest that it is necessary to recognize that there are differences between the cytological findings of G3 EA and the usual features of G1-2 EA.

  20. The relationship between single nucleotide polymorphisms in estrogen-metabolizing genes CYP1A1,CYP17,COMT and estrogen receptor alpha and the risk of endometrial adenocarcinoma among the Chinese women

    Institute of Scientific and Technical Information of China (English)

    Yang Xingsheng; Liu Jie; Zhong Yanhui; Zhang Xian; Wang Yan

    2007-01-01

    Objective:To explore whether polymorphisms of the genes responsible for catechol estrogen(CE) formation via estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and CE inactivation (COMT) and ERa are associated with an elevated risk for endometrial adenocarcinoma in Chinese women.Methods:A multigenic case-control study was conducted,eighty-seven endometrial adenocarcinoma patients and ninety controls were recruited.PCR-RFLP assays were used to determine the genotypes of estrogen-metabolizing genes and ERa gene.Results:The endometrial adenocarcinoma risk associated with individual susceptibility genotypes varied among the six polymorphic sites and was the highest for CYP17,followed by CYP1A1 Ile-Val,CYP1A1 MspI,COMT,ERa XbaI and ERa PvuII.Multivariate logistic regression showed the CYP1A1 MspI genotype was the most significant determinant for endometrial adenocarcinoma development and was associated with a 3.61 fold increase in risk (95% confidence interval,1.73~7.55).Furthermore,a trend of increasing risk for developing endometrial adenocarcinoma was found in women harboring higher numbers of high-risk genotypes.Conclusion:The CYP1A1,CYP17 and ERa XbaI genotypes are related to the susceptibility of endometrial adenocarcinoma,they may be useful markers for predicting endometrial adenocarcinoma susceptibility.The allele encoding for low acticity COMT,ERa PvuII may not be a genetic risk factor for endometrial adenocarcinoma.

  1. Measurement of endometrial thickness by transvaginal ultrasonography to predict pathological response to medroxyprogesterone acetate in patients with grade 1 endometrioid adenocarcinoma.

    Science.gov (United States)

    Sato, Masakazu; Arimoto, Takahide; Kawana, Kei; Miyamoto, Yuichiro; Ikeda, Yuji; Tomio, Kensuke; Tanikawa, Michihiro; Sone, Kenbun; Mori-Uchino, Mayuyo; Tsuruga, Tetsushi; Nagasaka, Kazunori; Adachi, Katsuyuki; Matsumoto, Yoko; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-04-01

    The aim of the present study was to evaluate whether measuring endometrial thickness during fertility-sparing treatment with medroxyprogesterone acetate (MPA) can be a predictive marker for effectiveness in women with endometrioid adenocarcinoma, grade 1 (EmCa, G1). A total of 32 patients with stage IA EmCa, G1 underwent treatment with MPA. Patients were 5 mm at week 16 was an independent factor for prediction of non-CR. Measurement of endometrial thickness during MPA treatment may be useful as a predictive marker for pathological response to MPA in patients with EmCa, G1.

  2. Reproducibility determination of WHO classification of endometrial hyperplasia/well differentiated adenocarcinoma and comparison with computerized morphometric data in curettage specimens in Iran

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    Meysamie Ali

    2009-03-01

    Full Text Available Abstract Background Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability. Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases. Methods A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS. Results The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement. Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined. Interobserver agreement was in substantial rate for simple hyperplasia (SH and well differentiated adenocarcinoma (WDA but was in fair limit for complex hyperplasia (CH and atypical hyperplasia (AH. Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH ( D Score ≥ 1 or VPS ≥ 55% and Endometrial Intraepithelial Neoplasia (EIN (D-Score Conclusion It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and

  3. P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

    Science.gov (United States)

    Jiang, Zhongyong; Xu, Wanqing; Dan, Gang; Liu, Yuan; Xiong, Jie

    2016-01-01

    Background Endometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women’s health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated. Material/Methods Normal endometrium, endometrial polyps, uterine adenomyosis, and endometrial adenocarcinoma tissue samples were collected. Real-time PCR was used to detect p53 and MDM2 mRNA expression. Immunohistochemical staining and Western blot analysis were applied to test p53 and MDM2 protein expression. Their correlation with clinical staging of endometrial adenocarcinoma was analyzed. Results P53 and MDM2 mRNA and protein expression were significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group compared with the normal control group (Pendometrial adenocarcinoma compared with endometrial polyps (P0.05). P53 and MDM2 mRNA and protein level showed a positive correlation. Significantly higher expression of p53 or MDM2 was observed in patients with stage III compared to those in patients with stage II. Higher expression was also observed in patients with stage II than in patients with stage I. Conclusions P53 and MDM2 mRNA and protein were elevated in endometrial polyps and endometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrial adenocarcinoma. They can promote cancer occurrence and development, and can be treated to assist diagnosis and provide a reference for treatment. PMID:27924072

  4. The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interacttions in vitro

    DEFF Research Database (Denmark)

    Petersen, A; tin-Ley, U; Ravn, V

    2005-01-01

    OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell...

  5. 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.

  6. Quantitative assessment of DNA methylation for the detection of cervical and endometrial adenocarcinomas in liquid-based cytology specimens.

    Science.gov (United States)

    Kim, Ga-Eon; Kweon, Sun-Seog; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan

    2012-08-01

    To investigate the aberrant promoter hypermethylation as a screening tool for cervical adenocarcinomas (CAs) and endometrial adenocarcinomas (EAs) in cervical scrapings. A quantitative multiplex methylation-specific polymerase chain reaction approach was used to examine promoter methylation of 5 genes (APC, HIN-1, RAR-beta, RASSF1A and Twist) in biopsy-confirmed CA (n = 31) and EA (n = 27) residual, liquid-based cytology samples. The data of negative for intraepithelial lesions or malignancy and low-grade squamous intraepithelial lesions were used as controls. Methylation levels of APC, RAR-beta, RASSF1A and Twist were significantly higher in CA than in control cervical samples. For EA, only the methylation levels of RASSF1A differed significantly from those of control. Receiver-operating characteristic analysis demonstrated that APC, RAR-beta and RASSF1A had the ability to distinguish CA/EA, CA and EA from control samples. In CA/EA and CA samples, the best 3-gene combination was RASSF1A/RAR-beta/APC. This 3-gene panel had a sensitivity of 87.0% for CA/EA and of 80.6% for CA and a specificity of 79.3% for both CA/EA and CA. In EA samples, RASSF1A showed the best performance in distinguishing EA from control. The estimated sensitivity of RASSF1A for detecting EA was 63.0%, and its specificity was 96.3%. This feasibility study demonstrates that quantitative detection of aberrant DNA methylation in cervical scrapings may be a promising new diagnostic tool for the detection of CA and EA.

  7. Reconstruction of endometrium from human endometrial side population cell lines.

    Directory of Open Access Journals (Sweden)

    Irene Cervelló

    Full Text Available Endometrial regeneration is mediated, at least in part, by the existence of a specialized somatic stem cell (SSC population recently identified by several groups using the side population (SP technique. We previously demonstrated that endometrial SP displays genotypic, phenotypic and the functional capability to develop human endometrium after subcutaneous injection in NOD-SCID mice. We have now established seven human endometrial SP (hESP cell lines (ICE 1-7: four from the epithelial and three from the stromal fraction, respectively. SP cell lines were generated under hypoxic conditions based on their cloning efficiency ability, cultured for 12-15 passages (20 weeks and cryopreserved. Cell lines displayed normal 46XX karyotype, intermediate telomerase activity pattern and expressed mRNAs encoding proteins that are considered characteristic of undifferentiated cells (Oct-4, GDF3, DNMT3B, Nanog, GABR3 and those of mesodermal origin (WT1, Cardiac Actin, Enolase, Globin, REN. Phenotype analysis corroborated their epithelial (CD9+ or stromal (vimentin+ cell origin and mesenchymal (CD90+, CD73+ and CD45⁻ attributes. Markers considered characteristic of ectoderm or endoderm were not detected. Cells did not express either estrogen receptor alpha (ERα or progesterone receptor (PR. The hESP cell lines were able to differentiate in vitro into adipocytes and osteocytes, which confirmed their mesenchymal origin. Finally, we demonstrated their ability to generate human endometrium when transplanted beneath the renal capsule of NOD-SCID mice. These findings confirm that SP cells exhibit key features of human endometrial SSC and open up new possibilities for the understanding of gynecological disorders such as endometriosis or Asherman syndrome. Our cell lines can be a valuable model to investigate new targets for endometrium proliferation in endometriosis.

  8. Androgen responsiveness of the new human endometrial cancer cell line MFE-296.

    Science.gov (United States)

    Hackenberg, R; Beck, S; Filmer, A; Hushmand Nia, A; Kunzmann, R; Koch, M; Slater, E P; Schulz, K D

    1994-04-01

    MFE-296 endometrial cancer cells express androgen receptors in vitro. These cells, which are tumorigenic in nude mice, are derived from a moderately differentiated human endometrial adenocarcinoma. They express vimentin and the cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of the cells. No marker chromosomes were observed. DNA analyses confirmed the genetic identity of the cell line and the patient from whom the cell line was derived. Proliferation of MFE-296 cells was inhibited by the progestin R5020 and the androgen dihydrotestosterone (DHT). The inhibition of proliferation by DHT was antagonized by the antiandrogen Casodex, demonstrating the involvement of the androgen receptor. Androgen binding was determined at 22,000 binding sites per cell using a whole-cell assay (KD = 0.05 nM) and 30 fmol/mg protein with the dextran charcoal method; 7 fmol/mg protein of progesterone receptors were found, whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor was functionally intact, as demonstrated by transfection experiments with a reporter-gene construct, containing an androgen-responsive element. In MFE-296 cells the content of the androgen receptor was up-regulated by its own ligand.

  9. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent....../inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas....

  10. Effect of anthralin on cell viability in human prostate adenocarcinoma.

    Science.gov (United States)

    Raevskaya, A A; Gorbunova, S L; Savvateeva, M V; Severin, S E; Kirpichnikov, M P

    2012-07-01

    The study revealed the key role of serine protease hepsin activity in transition of in situ prostate adenocarcinoma into the metastasizing form. Inhibition of hepsin activity suppresses the invasive growth of the tumor. Hepsin is an convenient target for pharmacological agents, so the study of its inhibitory mechanisms is a promising avenue in drug development. Assay of proteolytic activity in various tumor cell lines in vitro showed that this activity in prostate adenocarcinoma cells significantly surpasses proteolytic activity in other examined tumor cell lines. Selective cytotoxic action of anthralin, an inhibitor of hepsin activity, on human adenocarcinoma cells was demonstrated in comparison with other tumor cell lines.

  11. AngⅡ及AT1R在子宫内膜腺癌的表达及临床意义%Expressions of Ang Ⅱ and AT1R in endometrial adenocarcinoma and clinical significance

    Institute of Scientific and Technical Information of China (English)

    赵万成; 杨清; 王玉

    2011-01-01

    Objective :To observe the expressions of angiotensin Ⅱ ( Ang Ⅱ ) and Ang Ⅱ type 1 receptor ( AT1R ) in the endometrial adenocarcinoma. Methods : SP immunohistochemical method was performed to detecl the expressions of Ang Ⅱ and AT1R in the endometrial adenocarcinoma tissues ( n = 50 ) , endometrial atypical hypcrplasia tissues ( n = 15 ) and normal endometrial tissues( n = 10) . Result : Ang Ⅱ and AT1R were localized in the cytoplasm and cell membrane, and both were mostly expressed diffusely. The rates of positive expression of Ang Ⅱ in normal endometrial tissues、endometrial atypical hyperplasia tissues and endometrial adenocarcinoma tissues were10% ,47% ,86% ;The rates of positive expression of AT1R in the three groups were 20% ,33%,72%. The expressions of Ang Ⅱ and AT1R were higher in the endometrial adenocarcinoma tissues than those in the endometrial atypical hyperplasia tissues and normal endometrial tissues( P<0. 05) ;there was no significant difference in the expression of Ang Ⅱ and AT1R in endometrial atypical hyperplasia tissues and normal endometrial tissues( P>0. 05) . There was no significant difference in the expression of Ang Ⅱ in the endometrial adenocarcinoma tissues of different grades ( P>0. 05 ) ; the expression of AT1R was significantly higher in grade Ⅰ and Ⅱ than grade Ⅲ ,but there was no difference between grade Ⅰ and Ⅱ.Differences were insignificant in the expressions of Ang Ⅱ and ATIR not only between the superficial layer and deep layer of endometrium invades by the endometrial adenocarcinoma but also between the lymph node metastasis group and non-lymph node metastasis group ( P>0. 05) . Conclusion :Ang Ⅱ and AT1R may be associated with the differentiation of endometrial adenocarcinoma,and are possihly involved in the occurrence and development of endometrialadenocarcinoma. Use of selective AT1 antagonists may provide a new target for preventing and treating endometrial adenocarcinoma

  12. Response-specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long-term exposure to medroxyprogesterone acetate.

    Science.gov (United States)

    Zhao, Shunjun; Li, Genxia; Yang, Li; Li, Lei; Li, Hongyu

    2013-01-01

    Progestins, particularly medroxyprogesterone acetate (MPA), have for a long time been used as conservative treatment for young patients with clinical stage I, grade I endometrial carcinoma. However, more than 30% of patients with endometrial adenocarcinoma display resistance to endocrine therapies at the time of presentation and most cancer patients that initially respond to progestin treatment will at some point develop resistance, resulting in tumor progression. The cellular mechanisms underlying acquired resistance to progestin are poorly understood. In order to investigate the molecular mechanisms whereby human endometrial adenocarcinoma develops resistance to progestin therapy, we have undertaken to develop human endometrial adenocarcinoma cell lines that are resistant to the growth-inhibitory effects of progestins in vitro. A progestin-resistant subcell line of Ishikawa cells was developed from Ishikawa human endometrial adenocarcinoma cells by stepwise selection in increasing concentrations of the synthetic progestin, MPA, over ten months. The doubling time of the progestin-resistant cells (34.18±3.15 h) grown routinely in the medium containing 10 μM MPA was not significantly different from the doubling time of the parent Ishikawa cells (35.14±2.68 h) grown in the absence of MPA (t=-0.331, P=0.762). Moreover, the effect of treatment with MPA shifted from suppression of growth and invasiveness, as observed in the parent Ishikawa cells, to stimulation of growth and invasiveness in the progestin-resistant Ishikawa cells. The positive rates of estrogen receptor a (ERα) and progesterone receptor B (PRB) of the progestin-resistant Ishikawa cells were significantly reduced, whilst the positive rate of ERβ was significantly enhanced compared to the parent Ishikawa cells. These differences were statistically significant (PIshikawa cells may give rise to a resistance effect to MPA. When the resistant subtype is acquired, treatment with MPA enhances cancer cell

  13. Expression and Significance of Livin and p53 Protein in Endometrial Adenocarcinoma%Livin 和 p53蛋白在子宫内膜腺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    张玉凤; 刘欣; 王丽

    2012-01-01

      Objective To study the expression and significance of Livin and p 53 protein in endometrial adenocarcinoma .Meth-ods Immunohistochemical method was used to detect the expression of Livin and p 53 protein in 50 cases of endometrial adenocarcinoma ,25 cases of atypical hyperplasia of endometrium and 15 cases of normal endometrium .Results The expression of Livin and p53 in endometrial adenocarcinoma was significantly higher than those in simple endometrial hyperplasia and endometrial atypical hyperplasia (P<0.05).There was significant difference in the expression of Livin and p 53 between endometrial adenocarcinomas of different histological grades (P<0.05). There was positively related between the expression of Livin and p 53 in endometrial adenocarcinoma (rs=0.423,P<0.01).Conclusion The abnormal expression of Livin and p53 may plays important roles in oneogenesis and progression of endometrial adenocarcinoma .Detection of Livin together with p53 is valuable for early diagnosis and evaluation of prognosis for endometrial adenocarcinoma .%  目的检测Livin和p53蛋白在子宫内膜腺癌中的表达,探讨二者在子宫内膜腺癌中的表达及意义.方法应用免疫组织化学方法检测50例子宫内膜腺癌组织、25例不典型增生子宫内膜组织、15例正常子宫内膜组织中Livin与p53蛋白的表达.结果 Livin和p53在子宫内膜腺癌组织中的表达均明显高于不典型增生和正常子宫内膜组织(P<0.05),Livin和p53的表达在子宫内膜腺癌不同组织学分级中差异有显著性(P<0.05). Livin与p53在子宫内膜腺癌中的表达存在正相关性(rs=0.423,P<0.01).结论 Livin和p53的异常表达可能在子宫内膜腺癌的发生、发展中有密切关系,对其联合检测有助于子宫内膜腺癌的早期诊断及预后.

  14. The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interacttions in vitro

    DEFF Research Database (Denmark)

    Petersen, A; Bentin-Ley, Ursula; Ravn, V

    2005-01-01

    OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell...... cultures. MAIN OUTCOME MEASURE(S): Blastocyst attachment rate on endometrial cell cultures; secretion of glycodelin and leukemia inhibitory factor into the culture medium measured by RIA and ELISA techniques; and expression of progesterone receptors, interleukin-1 receptor type-1, and integrin subunit beta...

  15. The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interactions in vitro

    DEFF Research Database (Denmark)

    Petersen, Astrid; Bentin-Ley, Ursula; Ravn, Vibeke

    2005-01-01

    OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell...... cultures. MAIN OUTCOME MEASURE(S): Blastocyst attachment rate on endometrial cell cultures; secretion of glycodelin and leukemia inhibitory factor into the culture medium measured by RIA and ELISA techniques; and expression of progesterone receptors, interleukin-1 receptor type-1, and integrin subunit beta...

  16. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

    Science.gov (United States)

    2016-03-17

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  17. The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas

    DEFF Research Database (Denmark)

    Baandrup, Louise; Thomsen, Louise T; Olesen, Tina Bech

    2014-01-01

    The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association....

  18. GENISTEIN INHIBITS PROLIFERATION OF HUMAN ENDOMETRIAL ENDOTHELIAL CELL IN VITRO

    Institute of Scientific and Technical Information of China (English)

    Gui-hua Sha; Shou-qing Lin

    2008-01-01

    Objective To explore the effect of genistein on proliferation of human endometrial endothefial cells (HEECs) and glandular epithelium.Methods In vitro HEECs and human endometrial cancer-1B cell (HEC-1B) were cultured with 0, 1, 10, 50,100, and 200 μmol/L of genistein alone or indicated concentrations of genistein combined with 0.2 or 1 nmol/L 17β- estradiol (17β-E2 ). Cell proliferation was determined by [ 3H ]-thymidine incorporation and cell cycle was measured by flow cytometry.Results After 96 hours of treatment, genistein inhibited the proliferation of HEECs in a dose-dependent manner.The stimulation index reduced from 100% (without genistein treatment ) to about 1% (200 μmol/L genistein).HEECs were arrested at G1/0 and G2/M phase when treated with genistein for 96 hours. When the concentration of genistein was 200 μmol/L, the percentages of HEECs at GI/0, G2/M, and S phase were 96.0%, 2. 1%, and 1.9%,respectively. However, when HEECs were treated without genistein, the percentages of HEECs at G1/0, G2/M, and S phase were 76. 7%, 8.5%, and 14. 7%, respectively. 17β-E2 could not influence the effects of genistein on the prolif-eration of HEECs. Meanwhile, genistein could suppress the proliferation of HEC-1B. If the stimulation index of HEC-1B was defined as 100% when HEC-1B was treated with different doses of 1713-E2 ( without genistein), it was 67%,19, as well as 32% when cell was supplemented with 200 μmoi/L genistein combined with 0, 0.2, or 1 nmol/L 17β-E2, respectively.Conclusion Genistein at the concentration of 200 μmol/L can sufficiently inhibit the proliferation of HEECs and endometrial glandular epithelium simultaneously in vitro.

  19. [Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women].

    Science.gov (United States)

    Jóźwik, Maciej; Jóźwik, Marcin; Modzelewska, Beata; Niewińska, Marta; Jóźwik, Michał

    2015-04-01

    The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.

  20. Expressions of MDM2, Livin and Caspase-3 protein and mRNA in endometrial adenocarcinomas%学位论文摘要

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Objective To investigate the relationship of the expression of MDM2,Livin and Caspase-3 protein and mRNA in the development of endometrioid adenocarcinoma (EA). Methods The expression levels of MDM2, Livin and Caspase-3 proteins and mRNA in EA tissues (n = 72), endometrial hyperplasia tissues (n = 60) and normal tissues ( n = 30) were examined by tissue microarray technique, immunohistochemistry( SP method) and in situ hybridization method. Results The positive expression rates of MDM2, Livin and Caspase-3 protein and mRNA in EA were respectively 80. 6% ( 58/72 ), 80. 6% ( 58/72 ), 33.3% ( 24/72 ) and 73.6% ( 53/72 ), 75.0% ( 54/72 ),27.8% (20/72). The positive rates of both MDM2 and Livin protein and mRNA in EA were higher than that in normal endometrium and endometrial hyperplasia( P < 0. 01 ). However, the positive rate of Caspase-3 in EA was lower than that in normal endometrium and endometrial hyperplasia( P < 0. 01 ). The positive expressions of MDM2 protein and mRNA were not related to the histological grade, FIGO stage, depth of invasion and lymph node metastasis. The positive expressions of Livin and Caspase-3 protein and mRNA were related to histological grade (P <0. 01 ,P <0.05 ), but they were not related to FIGO stage, depth of invasion and the lymph node metastasis. The expressions of MDM2, Livin and Caspase-3 protein were positively correlated with their mRNA. The expression of Livin was negatively correlated Caspase-3. Conclusion The expressions of MDM2, Livin and Caspase-3 protein and mRNA correlate with the dedvelopment and progression of EA, which may be valuable biomarkers to detect the early carcinogenesis and prognosis of EA.

  1. Choline Transporters in Human Lung Adenocarcinoma: Expression and Functional Implications

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Choline is an essential nutrient for cell survival and proliferation, however, the expression and function of choline transporters have not been well identified in cancer. In this study, we detected the mRNA and protein expression of organic cation transporter OCT3, carnitine/cation transporters OCTN 1 and OCTN2,and choline transporter-like protein CTL1 in human lung adenocarcinoma cell lines A549, H1299 and SPC-A-1.Their expression pattern was further confirmed in 25 human primary adenocarcinoma tissues. The choline uptake in these cell lines was significantly blocked by CTL1 inhibitor, but only partially inhibited by OCT or OCTN inhibitors. The efficacy of these inhibitors on cell proliferation is closely correlated with their abilities to block choline transport. Under the native expression of these transporters, the total choline uptake was notably blocked by specific PI3K/AKT inhibitors. These results describe the expression of choline transporters and their relevant function in cell proliferation of human lung adenocarcinoma, thus providing a potential"choline-starvation" strategy of cancer interference through targeting choline transporters, especially CTL1.

  2. Liquid-based endometrial cytology: the Florence and Bari experience.

    Science.gov (United States)

    Buccoliero, A M; Resta, L; Napoli, A; Taddei, G L

    2009-04-01

    Several diagnostic procedures are available to investigate the endometrium, i.e. sonography, hysteroscopy, biopsy, endometrial curettage and cytology. Among these, endometrial cytology is less commonly utilized. Although the use of cytology in the diagnosis of endometrial adenocarcinoma has already been proposed due to its low cost and simple execution, a general consensus has not been reached. The improvement of the diagnostic capacity of endometrial cytology following the introduction of a liquid-based method suggests that this test should be routinely used in endometrial diagnosis. The main advantages of this method are the reduction in confounding factors, the distribution of cells on a thin layer and the possibility to obtain more slides from the same sample. The aim of this article is to focus on the methodological procedures and diagnostic criteria in liquid-based endometrial cytology based on the experience in two Italian centres: Department of Pathology, University of Bari and Department of Human Pathology and Oncology, University of Florence. The sampling method used by the Bari authors consists in the collection of liquid for uterine distension during hysteroscopy, while the Florence group used an endometrial brush. The sensitivity and specificity at Bari were 75% and 83%, respectively, and were 94-100% and 95-100% at Florence, respectively. Endometrial cytology provided sufficient diagnostic material significantly more often than biopsy. We thus propose that endometrial cytology can be used in routine diagnosis either alone or in association with other diagnostic procedures in order to improve diagnostic accuracy.

  3. Telmisartan Induces Growth Inhibition, DNA Double-Strand Breaks and Apoptosis in Human Endometrial Cancer Cells

    Science.gov (United States)

    Koyama, Naoko; Nishida, Yoshihiro; Ishii, Terukazu; Yoshida, Toshie; Furukawa, Yuichi; Narahara, Hisashi

    2014-01-01

    Telmisartan, an angiotensin II receptor type 1 blocker, is often used as an antihypertension drug, and it has also been characterized as a peroxisome proliferator-activated receptor-gamma (PPARγ) ligand. The purpose of this study was to elucidate the antitumor effects of telmisartan on endometrial cancer cells. We treated three endometrial cancer cell lines with various concentrations of telmisartan, and we investigated the effects of the telmisartan on the cell proliferation, apoptosis, and their related measurements in vitro. We also administered telmisartan to nude mice with experimental tumors to determine its in vivo effects and toxicity. All three endometrial cancer cell lines were sensitive to the growth-inhibitory effect of telmisartan. The induction of apoptosis was confirmed in concert with the altered expression of genes and proteins related to the apoptosis. We also observed that DNA double-strand breaks (DSBs) were induced in HHUA (human endometrial cancer) cells by telmisartan treatment. In addition, experiments in nude mice showed that telmisartan significantly inhibited human endometrial tumor growth, without toxic side effects. Our results suggest that telmisartan might be a new therapeutic option for the treatment of endometrial cancers. PMID:24667764

  4. Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells.

    Directory of Open Access Journals (Sweden)

    Irene Cervelló

    Full Text Available During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC population. Here we explore the hypothesis that human endometrial side population (SP cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC.

  5. Studies of Differentially-Expressed Genes in Human Endometrial Cancer of Various Differentiated Grades

    Institute of Scientific and Technical Information of China (English)

    Bin Cai; David Hogg; Guangzhong Lu; Ling Liu; Xiaowei Xi; Wei Xu; Huifang Lu; Yongbin Yang; Xiaoping Wan

    2007-01-01

    OBJECTIVE To study the gene expression profiles of human endometrial cancers at various differentiaOted grade levels and to identify the genes related to differentiation of the endometrial cancers. METHODS cDNA microarray technology was used to analyze the differentially-expressed genes among different differentiated grades of 32 cases of endometrial cancer. Hierarchical cluster analysis (HCA) for the gene expression profiles of the cases was employed. RESULTS The tissue samples were grouped based on the various dif ferentiated tumor grades with 33 differentiation-related genes identified out (P<0.001). Based on the results from the HCA, the conformity rate was 91% among the 33 differentially-expressed genes and the analysis of pathological classification.CONCLUSION Genes related to the differentiation of endometrial cancer can be identified by using gene chips to analyze the expression profiles of endometrial cancers at various differentiated grades; HCA of the gene expression profiles can be helpful for distinguishing high-risk endometrial cancers before surgery.

  6. Development of endometrioid adenocarcinoma despite Levonorgestrel-releasing intrauterine system: a case report with discussion and review of the RCOG/BSGE Guideline on the Management of Endometrial Hyperplasia.

    Science.gov (United States)

    van der Meer, A C L; Hanna, L S

    2017-02-01

    Obesity is a significant risk factor for the development of endometrial hyperplasia and cancer. More conservative prevention and management strategies are attractive due to the increased surgical risk and complication rates associated with obesity. The Levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) has been shown to reduce the risk of developing endometrial cancer. The recent joint Green Top Guideline on the Management of Endometrial Hyperplasia published by the Royal College of Obstetricians and Gynaecologists (RCOG) with the British Society for Gynaecological Endoscopy (BSGE) recommends the LNG-IUS for the medical management of endometrial hyperplasia without atypia. This case study reports on the development of endometrioid adenocarcinoma despite the presence of an LNG-IUS following a negative hysteroscopy in a 56-year-old woman with morbid obesity. This report highlights the need for patients and clinicians to remain vigilant to the early warning signs of developing endometrial cancer, especially in those at an increased risk secondary to obesity. © 2016 World Obesity Federation.

  7. 子宫内膜腺癌中MMP-2、MMP-9表达的免疫组化研究%Metalloproteinase-9(MMP-9)in Endometrial Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    仲肖静; 颜丽丽

    2014-01-01

    目的:探讨基质金属蛋白酶-2、-9(Matrix metalloproteinases,MMP)在子宫内膜腺癌组织中的表达及其与临床病理关系。方法:应用免疫组化SP法检测MMP-2、MMP-9在不同子宫内膜组织中的表达情况。结果:MMP-2在正常子宫内膜、子宫内膜增生症和子宫内膜腺癌组织中的阳性表达率分别为15.0%、26.7%、88.0%, MMP-9的阳性表达率分别为25.0%、33.3%、95.0%,MMP-2和MMP-9的表达在子宫内膜腺癌中均明显高于正常子宫内膜、子宫内膜增生症,比较差异均有统计学意义(P<0.05)。MMP-2、MMP-9的表达强度与子宫内膜腺癌的手术-病理分期、组织学分级、肌层浸润和淋巴结转移相关,差异均有统计学意义(P<0.05)。结论:MMP-2、MMP-9在子宫内膜腺癌的发生、发展过程中起促进作用,且两者表达与子宫内膜腺癌的浸润深度和转移程度有关,为早期诊断子宫内膜腺癌以及子宫内膜腺癌的预后判断、靶向治疗提供了可靠的依据。%Objective:To investigate the expression of MMP-2 and MMP-9 in endometrial adenocarcinoma tissue and its relation to clinical pathological characteristics.Method:Expression of MMP-2 and MMP-9 was examined by immunohistochemistry(SP method)in three different kinds of endometrium.Result:The results showed that the positive rates of MMP-2 in normal endometria,endometrial hyperplasias and endometrial adenocarcinomas were 15.0%,26.7%and 88.0%respectively,the positive rates of MMP-9 were 25.0%,33.3%and 95.0%respectively.Expression of MMP-2 and MMP-9 were significantly higher in endometrial adenocarcinoma than those in hyperplastic and normal endometria, the differences were statistically significant(P<0.05).In endometrial adenocarcinoma tissue,the positive expression of MMP-2 and MMP-9 was correlated with clinical pathological characteristics,histodifferentiation,myometrial invasion and lymphatic metastasis,the differences were statistically

  8. The effect of stem cell factor on proliferation of human endometrial CD146+ cells

    Directory of Open Access Journals (Sweden)

    Mehri Fayazi

    2016-07-01

    Full Text Available Background: Stem cell factor (SCF is a transcriptional factor which plays crucial roles in normal proliferation, differentiation and survival in a range of stem cells. Objective: The aim of the present study was to examine the proliferation effect of different concentrations of SCF on expansion of human endometrial CD146+ cells. Materials and Methods: In this experimental study, total populations of isolated human endometrial suspensions after fourth passage were isolated by magnetic activated cell sorting (MACS into CD146+ cells. Human endometrial CD146+ cells were karyotyped and tested for the effect of SCF on proliferation of CD146+ cells, then different concentrations of 0, 12.5, 25, 50 and 100 ng/ml was carried out and mitogens-stimulated endometrial CD146+ cells proliferation was assessed by MTT assay. Results: Chromosomal analysis showed a normal metaphase spread and 46XX karyotype. The proliferation rate of endometrial CD146P + P cells in the presence of 0, 12.5, 25, 50 and 100 ng/ml SCF were 0.945±0.094, 0.962±0.151, 0.988±0.028, 1.679±0.012 and 1.129±0.145 respectively. There was a significant increase in stem/ stromal cell proliferation following in vitro treatment by 50 ng/ml than other concentrations of SCF (p=0.01. Conclusion: The present study suggests that SCF could have effect on the proliferation and cell survival of human endometrial CD146P+P cells and it has important implications for medical sciences and cell therapies

  9. Identification of differently expressed genes in human colorectal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yao Chen; Yi-Zeng Zhang; Zong-Guang Zhou; Gang Wang; Zeng-Ni Yi

    2006-01-01

    AIM: To investigate the differently expressed genes in human colorectal adenocarcinoma.METHODS: The integrated approach for gene expression profiling that couples suppression subtractive hybridization, high-throughput cDNA array, sequencing,bioinformatics analysis, and reverse transcriptase realtime quantitative polymerase chain reaction (PCR)was carried out. A set of cDNA clones including 1260SSH inserts amplified by PCR was arrayed using robotic printing. The cDNA arrays were hybridized with florescent-labeled probes prepared from RNA of human colorectal adenocarcinoma (HCRAC) and normal colorectal tissues.RESULTS: A total of 86 genes were identified, 16 unknown genes and 70 known genes. The transcription factor Sox9 influencing cell differentiation was downregulated. At the same time, Heat shock protein 10 KDis downregulated and Calmoulin is up-regulated.CONCLUSION: Downregulation of heat shock protein 10 KD lost its inhibition of Ras, and then attenuated the Ras GTPase signaling pathway, increased cell proliferation and inhibited cell apoptosis. Down-regulated transcription factor Sox9 influences cell differentiation and cell-specific gene expression. Down-regulated Sox9 also decreases its binding to calmodulin, accumulates calmodulin as receptor-activated kinase and phosphorylase kinase due to the activation of PhK.

  10. Activation of Raf-1 in human pancreatic adenocarcinoma.

    Science.gov (United States)

    Berger, D H; Jardines, L A; Chang, H; Ruggeri, B

    1997-04-01

    Point mutations in the Ras oncogene cause Ras to remain in its active GTP-bound state sending signals downstream continuously. Since 75 to 90% of all human pancreatic ductal adenocarcinomas harbor activating mutations at codon 12 of the K-ras oncogene it was our belief that Raf-1-MEK-MAPK will be activated in the majority of human pancreatic cancers. The aim of this study was to confirm activation of Raf-1 in K-ras mutant human pancreatic cancer. Additionally, we sought to determine if Raf-1 activation differed in K-ras mutant and nonmutant pancreatic cancer. Furthermore, we were interested in determining if Raf-1 activation in pancreatic cancer led to subsequent activation of downstream effectors such as MAP kinase. The presence of mutations in codon 12 of the K-ras oncogene in 14 human pancreatic adenocarcinoma cell lines was determined by use of mutant allele-specific PCR restriction fragment length polymorphism analysis. Raf-1 expression of quiescent cells was determined by immunoblotting using a rabbit anti-human polyclonal antibody and enhanced chemiluminescence. MAP kinase activity was determined by measuring the incorporation of phosphate into Myelin Basic Protein. Seven cell lines were noted to have mutations in codon 12 of K-ras while seven cell lines did not. There was no difference in expression of the 74 kDa-activated form of Raf-1 in K-ras mutant vs K-ras nonmutant cell lines. However, there was a significant increase in MAP kinase activity in the nonmutant cell lines compared to the cell lines with Ras mutations (P = 0.026). We conclude that Raf-1 is expressed in its active form in human pancreatic cancer regardless of K-ras status. However, signalling downstream of Raf-1 differs in cell lines with K-ras mutations compared to those cell lines without K-ras mutations.

  11. Augmentation of arginase Ⅱ expression in the human endometrial epithelium in the secretory phase.

    Science.gov (United States)

    Tajima, Makiko; Harada, Tatsuya; Ishikawa, Tomonori; Iwahara, Yuki; Kubota, Toshiro

    2012-12-03

    L-arginine is the common substrate for arginase and nitric oxide synthase (NOS). Arginase converts L-arginine to urea and L-ornithine. L-Ornithine is the principal precursor for the production of polyamines and L-proline, which are required for cell proliferation and collagen synthesis. Endothelial NOS is expressed in the human endometrial glandular epithelium, but the expression and physiological roles of arginase in the human endometrium are not clear. The objective of this study was to investigate the expression and distribution patterns of arginases Ⅰ (A-Ⅰ) and Ⅱ (A-Ⅱ) in the human endometrium by using immunohistochemistry, reverse transcription-polymerase chain reaction (RTPCR), and western blotting. A-Ⅰ and A-Ⅱ were detected by immunohistochemistry in human endometrial epithelial cells during the proliferative and secretory phases of the menstrual cycle. RT-PCR showed that A-Ⅰ and A-Ⅱ mRNA were expressed in human endometrial tissue. Western blotting analysis results showed the expression of A-Ⅱ protein. Immunohistochemistry and western blotting results showed that expression levels of A-Ⅱ were significantly higher in the secretory phase than in the proliferative phase. Increased A-Ⅱ levels in the secretory phase may be responsible for endometrial growth by increasing polyamines and proline products.

  12. Twist在子宫内膜腺癌的表达及其与临床生物学行为的关系%Expression of Twist in endometrial adenocarcinoma and its relationship with clinical biological behaviors

    Institute of Scientific and Technical Information of China (English)

    杨丞; 饶翔

    2013-01-01

    Objective To investigate the expression and significance of Twist protein in atypical hyperplasia and endometrial adenocarcinoma. Methods Thirteen samples of normal endometrium, 25 of atypical hyperplasia, 54 of endometrial adenocarcinoma were collected. The expression of Twist protein was detected by immunohistochemis try, and its relationship with clinical biological behaviors of endometrial adenocarcinoma was analyzed. Results The expression rates of Twist protein in normal endometrium, atypical hyperplasia, endometrial adenocarcinoma were 15.4% (2/13), 48.0% (12/25), 74.1% (40/54), respectively. The differences between the three groups were statistically significant (P0.05). Conclusion Over-expression of Twist protein in endometrial atypical hyperplasia and endometrial adenocarcinoma is correlated with development of carcinoma. The protein could be used as one of the valuable reference index for the diagnosis, differential diagnosis and prognosis of endometrial adenocarcinoma.%目的 研究Twist蛋白在非典型增生子宫内膜和子宫内膜腺癌中的表达及其意义.方法 选取13例正常内膜组织、25例非典型增生内膜、54例子宫内膜腺癌,运用免疫组织化学方法检测Twist蛋白在各组织中表达情况,并分析其与子宫内膜腺癌的临床生物学行为的相关性.结果 正常子宫内膜、非典型增生内膜和子宫内膜腺癌中Twist蛋白阳性表达率分别为15.4% (2/13)、48.0% (12/25)、和74.1% (40/54),三组之间的阳性率差异均有显著统计学意义(P<0.01);在子宫内膜腺癌组中,Twist蛋白在Ⅲ级肿瘤中的阳性率明显高于Ⅰ、Ⅱ级肿瘤,肌层浸润深者阳性率高于肌层浸润浅者,ⅢA期阳性率高于Ⅰ~Ⅱ期,其差异均有统计学意义(P<0.05);而不同年龄的患者间比较,Twist蛋白阳性率差异无统计学意义(P>0.05).结论 Twist蛋白的过表达与子宫内膜非典型增生和腺癌的发生发展有关,可作为子宫内膜

  13. Expression of pRb2/p130 Gene in Human Endometrial Carcinoma Cells and the Significance%子宫内膜癌中pRb2/p130的表达及意义

    Institute of Scientific and Technical Information of China (English)

    支霜; 傅芬

    2009-01-01

    Objective To investigate the expression of pRb2/p130 gene and its relationship with the patholgical clinical features of human endometrial carcinoma.Methods The levels of pRb2/P130 protein were examined with immunohistochemical SP method in 28 smples of normal endometrial tissue,20 samples of atypical endometrial hyperplasia and 30 samples of endometrial adenocarcinomas.Results The positive rate of pRb2/p130 protein in the normal endometrium,atypical endometrial hyperplasia cells and endometrial adenocarcinoma cells was respectively 82.1%,55.0% and 23.3%.pRb2/p130 protein in endometrial atypical hyperplasia or endometrial adenocarcinoma was significantly lower than that in the normal tissue (P0.05).Conclusion Descent or deletion of the expression of pRb2/p130 gene is of a frequent incidence in human endometrial carcinoma.The positive rate of pRb2/p130 expression is reversly proportionate to malignant degree of endometrial carcinoma,which indicats that pRb2/p130 plays an important role in the development and pathogenesis of endometrial carcinoma.%目的 探讨子宫内膜组织中pRb2/p130的表达及其与子宫内膜癌临床病理特征的关系.方法 应用免疫组化SP法检测pRb2/p130在28例正常增生期子宫内膜、20例不典型增生子宫内膜、30例子宫内膜腺癌组织中的表达.结果 pRb2/p130阳性表达率在正常增生期子宫内膜、不典型增生子宫内膜、子宫内膜腺癌组织中依次递减(分别为82.1%、55.0%、23.3%),且子宫内膜腺癌和不典型性增生中明显低于正常增生期子宫内膜,差异均有统计学意义(P0.05).结论 在子宫内膜癌中pRb2/p130的表达下降或缺失是一个频发事情,其恶性度愈高阳性率愈低,提示pRb2/p130与子宫内膜癌的发生、发展密切相关,并在其发病机制中起着重要的作用.

  14. Establishment and characterization of a cell line (OMC-9) originating from a human endometrial stromal sarcoma.

    Science.gov (United States)

    Kakuno, Yoshiteru; Yamada, Takashi; Mori, Hiroshi; Narabayashi, Isamu

    2008-05-01

    Cell lines are very useful for clinical and basic research. The establishment of uterine malignant tumor cell lines with unusual histology is especially important. We describe the establishment and characterization of a new human endometrial stromal sarcoma cell line of the uterus. The cell line OMC-9 was established from a tumor mass in the uterine body of a 55-year-old woman. Characteristics of the cell line studied include morphology, chromosome analysis, heterotransplantation, tumor markers and chemosensitivity. This cell line has grown well for 196 months and has been subcultured more than 50 times. Monolayer cultured cells are polygonal in shape, appear to be spindle-shaped or multipolar and have a tendency to pile up without contact inhibition. The cells exhibit a human karyotype with a modal chromosomal number in the diploid range. The cells were able to be transplanted into the subcutis of nude mice and produced tumors resembling the original tumor. OMC-9 cells produced tissue polypeptide antigen. Both CD10, a sensitive and diagnostically useful marker of endometrial stromal neoplasms, and vimentin were identified immunohistochemically in the original tumor and the heterotransplanted tumor. The cells were sensitive to actinomycin D, doxorubicin, carboplatin, cisplatin and etoposide, drugs used commonly in the treatment of gynecologic cancer. Only three reports of uterine endometrial stromal sarcoma cell lines have thus far been reported in the literature. OMC-9 is the first endometrial stromal sarcoma cell line in which CD10 expression and chemosensitivity have been identified.

  15. Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo-FISH, and allelotyping.

    Science.gov (United States)

    Adamovic, Tatjana; Trossö, Fredrik; Roshani, Leyla; Andersson, Lars; Petersen, Greta; Rajaei, Saide; Helou, Khalil; Levan, Göran

    2005-10-01

    The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer-related genes in the region. The analysis revealed that seven tumors contained large RNO6-derived homogeneously staining regions (HSRs) in addition to several normal or near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone-dependent tumor.

  16. Endometrial Intraepithelial Neoplasia (EIN) in endometrial biopsy specimens categorized by the 1994 World Health Organization classification for endometrial hyperplasia.

    Science.gov (United States)

    Li, Xiao-Chao; Song, Wen-Jing

    2013-01-01

    Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. β-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of β-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P hyperplasia, high β-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.

  17. Effects of Excess Copper Ions on Decidualization of Human Endometrial Stromal Cells.

    Science.gov (United States)

    Li, Ying; Kang, Zhen-Long; Qiao, Na; Hu, Lian-Mei; Ma, Yong-Jiang; Liang, Xiao-Huan; Liu, Ji-Long; Yang, Zeng-Ming

    2017-05-01

    The aim of this study was to investigate the effects of copper ions on decidualization of human endometrial stromal cells (HESCs) cultured in vitro. Firstly, non-toxic concentrations of copper D-gluconate were screened in HESCs based on cell activity. Then, the effects of non-toxic concentrations of copper ions (0~250 μM) were examined on decidualization of human endometrial stromal cells. Our data demonstrated that the mRNA expressions of insulin-like growth factor binding protein (IGFBP-1), prolactin (PRL), Mn-SOD, and FOXO1were down-regulated during decidualization following the treatments with 100 or 250 μM copper ions. Meanwhile, the amount of malonaldehyde (MDA) in the supernatant of HESCs was increased. These results showed that in vitro decidualization of HESCs was impaired by copper treatment.

  18. miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro.

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    Full Text Available Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human

  19. miRNA Signature and Dicer Requirement during Human Endometrial Stromal Decidualization In Vitro

    Science.gov (United States)

    Estella, Carlos; Herrer, Isabel; Moreno-Moya, Juan Manuel; Quiñonero, Alicia; Martínez, Sebastián; Pellicer, Antonio; Simón, Carlos

    2012-01-01

    Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs) decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human endometrial decidualization

  20. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Casal, Roberto; Bhattacharya, Chitralekha [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Epperly, Michael W. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Basse, Per H. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Hong [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Biostatistics, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Xinhui [Harvard Medical School, Harvard University, 25 Shattuck Street, Boston, MA 02115 (United States); Proia, David A. [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States); Greenberger, Joel S. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Socinski, Mark A.; Levina, Vera, E-mail: levinav@upmc.edu [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-05-22

    The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors.

  1. Derivation of Adipocytes from Human Endometrial Stem Cells (EnSCs)

    Science.gov (United States)

    Ai, Jafar; Shahverdi, Ahmad Reza; Barough, Somayeh Ebrahimi; Kouchesfehani, Homa Mohseni; Heidari, Saeed; Roozafzoon, Reza; Verdi, Javad; Khoshzaban, Ahad

    2012-01-01

    Background Due to increasing clinical demand for adipose tissue, a suitable cell for reconstructive adipose tissue constructs is needed. In this study, we investigated the ability of Human Endometrial-derived stem cells (EnSCs) as a new source of mesenchymal stem cells to differentiate into adipocytes. EnSCs are the abundant and easy available source with no immunological response, for cell replacement therapy. Methods Single-cell suspensions of EnSCs were obtained from endometrial tissues from 10 women experiencing normal menstrual cycles, and were cultured at clonal density (10 cells/cm 2) or limiting dilution. Endometrial mesenchymal stem cell markers were examined flow cytometry. These cells were treated with adipogenic-inducing medium for 28 days. The adipogenic differentiation of the EnSC was assessed by cellular morphology and further confirmed by Oil Red O staining and RT-PCR. The BM-MSC differentiated into adipocytes in the presence of adipogenic stimuli for 3 weeks. Results The flow cytometric analysis showed that the cells were positive for CD90, CD105, CD146 and were negative for CD31, CD34.We showed that the key adipocytes marker PPARa was expressed in mRNA level after 28 days post treatment (PT). Conclusion According to our finding, it can be concluded that EnSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage. PMID:23926540

  2. Silencing nc886, a Non-Coding RNA, Induces Apoptosis of Human Endometrial Cancer Cells-1A In Vitro

    Science.gov (United States)

    Hu, Zhuoying; Zhang, Hongyu; Tang, Liangdan; Lou, Meng; Geng, Yanqing

    2017-01-01

    Background The role that nc886, a non-coding microRNA, plays in human endometrial cancer is unknown. The present study aimed to describe the functional role of nc886 in human endometrial cancer-1A (HEC-1A) cell line, which may provide another target for human endometrial cancer treatment. Material/Methods The expression levels of nv886 in normal human endometrial tissue and the early phase and late phase of human endometrial cancer tissues were determined and compared by fluorescence in situ hybridization (FISH). Small interference RNA (siRNA) was used to inhibit nc886, and cell proliferation was evaluated with the MTT test. mRNA levels of PKR, NF-κB, vascular endothelial growth factor (VEGF), and caspase-3 were determined against glyceraldehyde 3-phosphate dehydrogenase (GAPDH between the HEC-1A control group and the silenced group (nc886 silenced with siRNA) by real-time reverse transcription polymerase chain reaction (RT-PCR). The protein levels of PKR (total and phosphorylated form), NF-κB, VEGF, and caspase-3 were determined against GAPDH by Western blotting, and cell apoptosis was determined by flow cytometry. Results Our results indicated that a higher level of nc886 was expressed in the late phase of human endometrial cancer tissue, less than in the early phase but still higher than in normal human endometrial tissue. After nc886 was silenced, protein levels of p-PKR (phosphorylated PKR) and caspase-3 were increased, whereas NF-κB and VEGF were decreased. Conclusions The rate of apoptosis in the silenced group was increased and the rate of cell proliferation was slower in comparison to the control. PMID:28298621

  3. Expression of TBX2 and PAX9 in endometrial adenocarcinomas and their correlation%子宫内膜样腺癌中TBX2、PAX9的表达及其相关性

    Institute of Scientific and Technical Information of China (English)

    徐傲; 陈柯; 郭真理; 王晓秋

    2012-01-01

    目的 探讨TBX2、PAX9在正常子宫内膜、子宫内膜增殖症和子宫内膜样腺癌(endometrioid adenocarcinoma,EA)组织中的表达及临床病理学意义.方法 采用组织芯片技术和免疫组化检测30例正常子宫内膜组织、30例单纯性增生内膜、30例复杂伴不典型性增生内膜、82例EA组织中TBX2、PAX9蛋白的表达.结果 TBX2蛋白在子宫内膜样腺癌中的阳性表达率明显高于正常子宫内膜和子宫内膜增殖症(P均<0.01),TBX2过表达与组织学分级、临床分期、浸润程度均有相关性(P<0.01,P<0.05,P<0.01),与淋巴结转移无相关性(P>0.05);PAX9蛋白在子宫内膜样腺癌中的阳性表达率明显高于正常子宫内膜、子宫内膜单纯性增生(P均<0.01),而和复杂伴不典型性增生之间没有统计学意义(P>0.05),在复杂伴不典型增生中表达明显高于正常子宫内膜和单纯性增生内膜(P均<0.01),PAX9阳性表达与组织学分级、临床分期、浸润程度均有相关性(P<0.01,P<0.01,P<0.05),但与淋巴结转移无相关性(P>0.05).TBX2与PAX9蛋白呈正相关(rs=0.427,P<0.01).结论 TBX2和PAX9均在子宫内膜样腺癌中发生、发展中发挥重要作用,联合检测其表达可为子宫内膜样腺癌的早期诊断、预后判断提供有价值的指标.%Purpose To investigate the relationship between the expression of TBX2 and PAX9 proteins in the development of endome-trial carcinoma. Methods The expression levels of TBX2, PAX9 proteins in endometrial adenocarcinoma tissues ( n = 82 ), endometri-al hyperplasia tissues ( n = 60 ) and normal tissues ( n = 30 ) were examined by tissue microarray technique and immunohistochemistry ( SP method ). Results The positive expression rates of TBX2 protein in normal endometrium, endometrial simple hyperplasia, endometrial atypical hyperplasia and endometrial carcinomas were gradually increased ( P 0. 05 ). The positive of PAX9 protein in endometrial carcinomas was

  4. Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

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    Chi-Chang Chang

    2014-12-01

    Full Text Available Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer, Hep G2 (hepatoma, FaDu (pharynx squamous cancer, MDA-MB-231 (breast cancer, and especially on LNCaP (prostate cancer cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  5. Anti-proliferative effects of Siegesbeckia orientalis ethanol extract on human endometrial RL-95 cancer cells.

    Science.gov (United States)

    Chang, Chi-Chang; Hsu, Hsia-Fen; Huang, Kuo-Hung; Wu, Jing-Mei; Kuo, Shyh-Ming; Ling, Xue-Hua; Houng, Jer-Yiing

    2014-12-01

    Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  6. Effect of Adding Human Chorionic Gonadotropin to The Endometrial Preparation Protocol in Frozen Embryo Transfer Cycles

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    Maryam Eftekhar

    2012-01-01

    Full Text Available Background: Human chorionic gonadotropin (HCG, one of the initial embryonic signals, isprobably a major regulator of the embryo-endometrial relationship. This study aims to assess theadvantage of HCG supplementation during the secretory phase of hormonally prepared cycles forthe transfer of cryopreserved-thawed embryos.Materials and Methods: This study was a randomized clinical trial. Infertile women who werecandidates for frozen-thawed embryo transfers entered the study and were divided into two groups,HCG and control. The endometrial preparation method was similar in both groups: all women receivedestradiol valerate (6 mg po per day from the second day of the menstrual cycle and progesteronein oil (100 mg intramuscular (I.M. when the endometrial thickness reached 8 mm. Estradiol andprogesterone were continued until the tenth week of gestation. In the HCG group, patients received anHCG 5000 IU injection on the first day of progesterone administration and the day of embryo transfer.Results: In this study, 130 couples participated: 65 in the HCG group and 65 in the control group.There was no statistically significant difference between groups regarding basic characteristics.Implantation rate, chemical pregnancy, clinical pregnancy, ongoing pregnancy, and abortion rateswere similar in both groups.Conclusion: Although HCG has some advantages in assisted reproductive technology (ARTcycles, our study did not show any benefit of HCG supplementation during the secretory phase offrozen cycles (Registration Number: IRCT201107266420N4.

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

    Science.gov (United States)

    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.

  8. The Effect of Levonorgestrel on Fibrinolytic Factors in Human Endometrial Endothelial Cells.

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    Pakrashi, Tarita; Taylor, Joelle E; Nelson, Ashley; Archer, David F; Jacot, Terry

    2016-11-01

    The levonorgestrel-releasing intrauterine system is considered a highly effective treatment of heavy menstrual bleeding (HMB). While LNG has established effects on the stromal and glandular compartments of the endometrial tissue, its effect on the endometrial endothelial cells has not been investigated. We examined whether LNG regulates fibrinolytic factors, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) secreted by human endometrial endothelial cells (HEECs) and determined the steroid receptor through which LNG exerts its effect on the endothelium. The HEECs were treated with LNG or progesterone and levels of tPA and plasminogen activator inhibitor 1 (PAI-1) measured. The HEECs were specifically examined for the presence of androgen receptors through Western blot. Levonorgestrel ± flutamide were added to HEECs and the levels of tPA and uPA were examined. An enzyme-linked immunosorbent assay performed on culture media confirmed a statistically significant decrease in tPA levels in cells treated with LNG (77.80% ± 8.0% of control; n = 5, P < .05 vs control) but not progesterone. The androgen receptor (110 kDa) was detected in HEEC lysates. The decrease in tPA was blocked by the addition of flutamide (101.3% ± 16% of control), a classic nonsteroidal androgen receptor blocker. There was no change in uPA or PAI-1 levels in cells treated with LNG. Levonorgestrel decreases tPA levels through the androgen receptor in HEECs. Thus, LNG inhibits tPA secretion by the endometrial endothelial cell. This response suggests reduction in HMB with LNG-IUS could reflect an LNG-mediated promotion of hemostasis. © The Author(s) 2016.

  9. Leptin regulation of the interleukin-1 system in human endometrial cells.

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    Gonzalez, Ruben Rene; Leary, Kristen; Petrozza, John Christopher; Leavis, Paul Clifton

    2003-03-01

    We have previously shown that (i). leptin and leptin receptor (Ob-R) are expressed in the human endometrium, and (ii). leptin secretion is regulated in blastocyst and endometrial epithelial cell (EEC) co-cultures. Interleukin-1beta (IL-1beta) up-regulates leptin and Ob-R, and both cytokines up-regulate beta3 integrin expression in EEC. In the present investigation we examined the effect of leptin on the expression of the IL-1 system in EEC and endometrial stromal cells (ESC) cultured in a medium containing insulin, leptin or IL-1beta (0-3 nmol/l). Leptin stimulated IL-1 antagonist (IL-1Ra), IL-1beta secretion and expression of IL-1 receptor type I (IL-1R tI) in both cell types. IL-1beta and IL-1Ra secretion were down-regulated by IL-1R tI blockade using specific antibodies. Interestingly, leptin partially neutralized this effect. The blockade of Ob-R neutralized the effects of both leptin and IL-1beta on expression of the IL-1beta system and beta3 integrin and on phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that leptin regulates the IL-1 system and that the blockade of functional Ob-R impairs leptin and IL-1beta functions at the endometrial level. Leptin could be an important molecule for implantation and a molecular mediator for actions of the IL-1 system. The fact that leptin, in the absence of IL-1, can trigger the expression of markers of endometrial receptivity and of the invasive trophoblast phenotype (as does IL-1), suggest that leptin could substitute for these IL-1 functions during the implantation process.

  10. Challenging Regimen for Long-Term Conservative Treatment of Endometrial Adenocarcinoma in Young Women: A Case Report and Review of the Literature

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    Prasong Tanmahasamut

    2010-10-01

    Full Text Available A 20-year-old obese Thai woman with polycystic ovary syndrome and clinical stage I well-differentiated endometrial carcinoma denied surgical staging. Chest X-ray and magnetic resonance imaging of the whole abdomen suggested neither distance metastasis nor local invasion of the cancer. After 3 months of systemic progestin therapy with megestrol acetate (MA 480 mg/day, the endometrial carcinoma persisted. The treatment was changed to a combination of levonorgestrel intrauterine system (LNG-IUS and MA with a stepping-up from 160 to 480 mg/day. Complete remission was achieved at treatment month 9. Prevention of recurrence was provided using LNG-IUS plus MA 160 mg/day. Endometrial surveillance using trimonthly transvaginal ultrasonography and endometrial biopsy suggested no recurrence for at least 24 months after remission.

  11. 子宫内膜样腺癌组织GLUT-1和VEGF表达相关性分析%Expression of GLUT-1 and VEGF in endometrial adenocarcinoma tissues

    Institute of Scientific and Technical Information of China (English)

    方志文; 刘欣; 王丽; 于国华

    2012-01-01

    OBJECTIVE; To investigate the expression of glucose transporter protein-1(GLUT-1) end vascular endo-thelial growth factorC VEGF) in endometrial simple hyperplasia, complex hyperplasia.atypical hyperplasia and endoraettial adenocarcinoma. METHODS; The immunohistochcmical (PV9000 twostep) method was applied to detect the. expression of GLUT-1 and VEGF in the endometrial simple hyperplasia(15 cases) .complex hyperplasia. (12 cases), atypical hyper-plasia (18 cases) ,and endoinetrial adeno-carciaoma (36 cases). RESULTS, The difference of expression of GLUT-1 and VEGF in endometrial adenocarcinoma were 83. 3% and 75.0%,which were significantly different from those in endometrial simple hyperplasia, complex hyperplasia and atypical hyperplasia tissue were statistically Significant (P <0. 05). There were positive correlation anmong GLUT-1 and VEGF (r-=0. 65,P<0. 01). CONCLUSIONS; GLUT-1 and VEGF can play important roles in the development of endometrial carcinoma. --The expression of GLUT-1 is positively associated with VEGF. They plsy important roles in the cercinogensis of endometrial carcioma and has certain value in clinieal ap-plication.%目的:通过检测葡萄糖转运蛋白-1 (GLUT-1)和血管内皮生成因子(VEGF)在子宫内膜病变中的表达,探讨其与子宫内膜样腺癌发生发展的关系.方法:应用免疫组化(PV9000二步法)检测36例子宫内膜样腺癌、18例子宫内膜不典型增生、12例复杂性增生和15例单纯性增生组织中GLUT-1和VEGF的表达.结果:GLUT-1和VEGF在子宫内膜样腺癌组织中的表达分别为83.3%和75.0%,与单纯性增生复杂性增生及不典型增生组织相比较,差异均有统计学意义,P<0.05.子宫内膜病变组织中GLUT-1与VEGF表达水平间存在正相关关系,r=0.65,P<0.01.结论:GLUT-1和VEGF在子宫内膜病变由良性到恶性转变过程中起重要作用.VEGF通过上调GLUT-1的表达,促进子宫内膜样腺癌的发生发展,具有临床应用价值.

  12. Sildenafil Effect on Nitric Oxide Secretion by Normal Human Endometrial Epithelial Cells Cultured In vitro

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    Farzaneh Chobsaz

    2011-01-01

    Full Text Available Background: Sildenafil is a selective inhibitor of cyclic-guanosine monphosphat-specificphosphodiesterase type 5. It increases intracellular nitric oxide (NO production in some cells.There are reports on its positive effect on uterine circulation, endometrial thickness, and infertilityimprovement. Endometrial epithelial cells (EEC play an important role in embryo attachment andimplantation. The present work investigates the effect of sildenafil on human EEC and their NOsecretion in vitro.Materials and Methods: In this experimental in vitro study, endometrial biopsies (n=10 werewashed in a phosphate buffered solution (PBS and digested with collagenase I (2 mg/ml in DMEM/F12 medium at 37°C for 90 minutes. Epithelial glands were collected by sequential filtrationthrough nylon meshes (70 and 40 μm pores, respectively. Epithelial glands were then treated withtrypsin to obtain individual cells. The cells were counted and divided into four groups: control and1, 10, and 20 μM sildenafil concentrations. Cells were cultured for 15 days at 37ºC and 5% CO2; themedia were changed every 3 days, and their supernatants were collected for the NO assay. NO wasmeasured by standard Greiss methods. Data were analyzed by one way ANOVA.Results: There was no significant difference between groups in cell count and NO secretion, but thelevel of NO increased slightly in the experimental groups. The 10 μM dose showed the highest cellcount. EEC morphology changed into long spindle cells in the case groups.Conclusion: Sildenafil (1, 10, and 20 μM showed a mild proliferative effect on human EECnumbers, but no significant change was seen in NO production.

  13. Prediction of histological types of endometrial cancer by endometrial cytology.

    Science.gov (United States)

    Okadome, Masao; Saito, Toshiaki; Nishiyama, Naoko; Ariyoshi, Kazuya; Shimamoto, Kumi; Shimada, Takako; Kodama, Keisuke; Imamura, Shogo; Nishiyama, Ken-ichi; Taguchi, Kenichi

    2014-07-01

    Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  14. Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

    Science.gov (United States)

    Pagani, Isabel; Ghezzi, Silvia; Ulisse, Adele; Rubio, Alicia; Turrini, Filippo; Garavaglia, Elisabetta; Candiani, Massimo; Castilletti, Concetta; Ippolito, Giuseppe; Poli, Guido; Broccoli, Vania; Panina-Bordignon, Paola; Vicenzi, Elisa

    2017-01-01

    Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line together with the induction of interferon-β (IFN-β) and of IFN-stimulated genes. Notably, in vitro decidualization of T-HESC with cyclic AMP and progesterone upregulated the cell surface expression of the ZIKV entry co-receptor AXL and boosted ZIKV replication by ca. 100-fold. Thus, endometrial stromal cells, particularly if decidualized, likely represent a crucial cell target of ZIKV reaching them, either via the uterine vasculature in the viremic phase of the infection or by sexual viral transmission, and a potential source of virus spreading to placental trophoblasts during pregnancy. PMID:28281680

  15. LeY oligosaccharide upregulates DAG/PKC signaling pathway in the human endometrial cells.

    Science.gov (United States)

    Li, Yali; Ma, Keli; Sun, Ping; Liu, Shuai; Qin, Huamin; Zhu, Zhengmei; Wang, Xiaoqi; Yan, Qiu

    2009-11-01

    LeY oligosaccharide is stage specifically expressed by the embryo and uterine endometrium, and it plays important roles in embryo implantation. In addition to participating in the recognition and adhesion on fetal-maternal interface, LeY potentially regulates the expression of some implantation-related factors. However, it remains elusive whether it can mediate the involved signaling pathway. In this study, agarose-LeY beads were used to mimic the embryos, and the effects of LeY oligosaccharide on DAG/PKC signaling pathway was studied in human endometrial epithelial cells. Results showed that LeY could significantly trigger the activation of cPKCalpha and cPKCbeta2, and their translocation from the cytosol to the plasma membrane. The cellular DAG content was also upregulated, and the activation of PLCgamma1 was promoted. On the contrary, DAG/PKC signaling pathway was significantly inhibited when anti-LeY antibody was used after confirmation of LeY expression in human endometrial epithelial cells by immunohistochemistry and flow cytometry. These results suggest that LeY oligosaccharide acts as a signal molecule to modulate DAG/PKC signaling pathway.

  16. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

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    Jiang, Yue; Hu, Yali; Zhao, Jing; Zhen, Xin [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Yan, Guijun, E-mail: yanguijun33@gmail.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Sun, Haixiang, E-mail: stevensunz@163.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)

    2011-01-14

    Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

  17. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    Science.gov (United States)

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  18. Microarray Analysis on Gene Regulation by Estrogen, Progesterone and Tamoxifen in Human Endometrial Stromal Cells

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    Chun-E Ren

    2015-03-01

    Full Text Available Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies.

  19. Microarray Analysis on Gene Regulation by Estrogen, Progesterone and Tamoxifen in Human Endometrial Stromal Cells

    Science.gov (United States)

    Ren, Chun-E; Zhu, Xueqiong; Li, Jinping; Lyle, Christian; Dowdy, Sean; Podratz, Karl C.; Byck, David; Chen, Hai-Bin; Jiang, Shi-Wen

    2015-01-01

    Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies. PMID:25782154

  20. Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

    Science.gov (United States)

    Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

    2015-01-01

    Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with

  1. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

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    Zhi Xu

    Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

  2. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

    Science.gov (United States)

    Ikari, Akira; Watanabe, Ryo; Sato, Tomonari; Taga, Saeko; Shimobaba, Shun; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Endo, Satoshi; Matsunaga, Toshiyuki; Sugatani, Junko

    2014-09-01

    Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.

  3. 子宫内膜腺癌组织中 IGFBP-rP1基因的甲基化状态及其 mR-NA、蛋白表达水平的检测%Detection of methylation of IGFBP-rP1 gene and relationship with its mR-NA and protein expressions in endometrial adenocarcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    郭瑞霞; 范丽君; 李艳敏

    2015-01-01

    目的:探讨子宫内膜腺癌组织中胰岛素样生长因子结合蛋白相关蛋白1( IGFBP-rP1)基因的甲基化状态及其与IGFBP-rP1 mRNA、蛋白表达之间的关系。方法:采用甲基化特异性PCR检测45例子宫内膜腺癌、30例子宫内膜单纯性增生和30例子宫内膜不典型增生组织中IGFBP-rP1基因启动子区和第一外显子区CpG岛的甲基化状态;采用实时荧光定量PCR和免疫组化SP法分别检测上述3种组织中IGFBP-rP1 mRNA和蛋白的表达。结果:子宫内膜腺癌组织中IGFBP-rP1基因在启动子区的甲基化率高于其在第一外显子区的甲基化率(χ2=6.429,P=0.011)。子宫内膜腺癌组织中IGFBP-rP1基因在启动子区的甲基化率低于子宫内膜不典型增生组织和单纯性增生组织(F=14.659,P=0.001)。子宫内膜腺癌组织中IGFBP-rP1 mRNA和蛋白的表达均高于子宫内膜不典型增生组织和单纯性增生组织(F=8.619、χ2=23.611,P均<0.05);在启动子区发生IGFBP-rP1基因甲基化的子宫内膜腺癌组织中,其mRNA的表达水平低于未甲基化组(t=4.758,P=0.001),其蛋白的表达与甲基化状态呈负关联(rP =-0.625,P<0.001)。结论:子宫内膜腺癌组织中IGFBP-rP1基因甲基化主要发生在启动子区,且呈低甲基化状态;IGFBP-rP1启动子区的低甲基化状态可能是IGFBP-rP1基因在子宫内膜腺癌组织中高表达的调控机制之一。%Aim:To investigate the methylation of insulin like growth factor binding protein-related protein 1( IGFBP-rP1 ) gene and its relationship with the expressions of IGFBP-rP1 mRNA and protein in endometrial adenocarcinoma tissue . Methods:Methylation-specific PCR was used to detect the methylation status of IGFBP-rP1 gene in the promoter region and the first exon region in 45 cases of endometrial adenocarcinoma ,30 cases of endometrial atypical hyperplasia , and 30 cases of

  4. Endometrial Hyperplasia

    Science.gov (United States)

    ... of certain conditions, such as diabetes mellitus , polycystic ovary syndrome, gallbladder disease, or thyroid disease Obesity Cigarette smoking Family history of ovarian, colon, or uterine cancer What are the types of endometrial hyperplasia? Endometrial ...

  5. Proteomic analysis identifies interleukin 11 regulated plasma membrane proteins in human endometrial epithelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Stanton Peter G

    2011-05-01

    Full Text Available Abstract Background During the peri-implantation period, the embryo adheres to an adequately prepared or receptive endometrial surface epithelium. Abnormal embryo adhesion to the endometrium results in embryo implantation failure and infertility. Endometrial epithelial cell plasma membrane proteins critical in regulating adhesion may potentially be infertility biomarkers or targets for treating infertility. Interleukin (IL 11 regulates human endometrial epithelial cells (hEEC adhesion. Its production is abnormal in women with infertility. The objective of the study was to identify IL11 regulated plasma membrane proteins in hEEC in vitro using a proteomic approach. Methods Using a 2D-differential in-gel electrophoresis (DIGE electrophoresis combined with LCMS/MS mass spectrometry approach, we identified 20 unique plasma membrane proteins differentially regulated by IL11 in ECC-1 cells, a hEEC derived cell line. Two IL11 regulated proteins with known roles in cell adhesion, annexin A2 (ANXA2 and flotillin-1 (FLOT1, were validated by Western blot and immunocytochemistry in hEEC lines (ECC-1 and an additional cell line, Ishikawa and primary hEEC. Flotilin-1 was further validated by immunohistochemistry in human endometrium throughout the menstrual cycle (n = 6-8/cycle. Results 2D-DIGE analysis identified 4 spots that were significantly different between control and IL11 treated group. Of these 4 spots, there were 20 proteins that were identified with LCMS/MS. Two proteins; ANXA2 and FLOT1 were chosen for further analyses and have found to be significantly up-regulated following IL11 treatment. Western blot analysis showed a 2-fold and a 2.5-fold increase of ANXA2 in hEEC membrane fraction of ECC-1 and Ishikawa cells respectively. Similarly, a 1.8-fold and a 2.3/2.4-fold increase was also observed for FLOT1 in hEEC membrane fraction of ECC-1 and Ishikawa cells respectively. In vitro, IL11 induced stronger ANXA2 expression on cell surface of primary h

  6. Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase-2 in human endometrial carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chen Mei; Bo Nai-xiu; Huang Ya-jun; Dai Qi; Gong Li-mei

    2010-01-01

    Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and its tissue inhibitor (TIMP-2) in endometrial carcinoma and analyze their significance in endometrial cancer′s invasion and metastasis. Methods: Endometrial tissues were collected from 64 patients with endometrial carcinoma, 20 patients with endometrial hyperplasia and 20 normal women. The expressions of MMP-7, TIMP-2 in endometrium were measured by immuohistochemistry. Results: Expressions of MMP-7, TIMP-2 in endometrium of patients with endometrial carcinoma were significantly higher than those in normal endometrium (P<0.05). MMP-7 expression increased with surgical-pathological staging, depth of myometrial invasion, histologic grades and lymph node metastasis (P<0.05), while TIMP-2 expression was related to lymph node metastasis (P<0.05). TIMP-2 expression in endometrial cancer was significantly higher than that in hyperplastic endometrium (P<0.05). Expressions of TIMP-2 and MMP-7 in endometrium of patients with endometrial carcinoma were positively correlated (r=0.654, P<0.001). Conclusion: Highly expressed MMP-7 and TIMP-2 in endometrium may be related to development, invasion and metastasis of endometrial cancers.

  7. Identification and characterization of SP cells in human lung adenocarcinoma SPC-A1 cells

    Directory of Open Access Journals (Sweden)

    Yanliang ZHU

    2008-10-01

    Full Text Available Background and objective Recently, eloquent studies from some solid tumors have provided proofs that cancers originate from cancer stem cells (CSC. The discovery of CSC has changed our view of carcinogenesis and chemotherapy. The aim of this study is to identify and characterize the CSC population that drives and maintains lung adenocarcinoma growth and metastasis. Methods Side population (SP cell analysis combined with serum-free media (SFM were applied to established human lung adenocarcinoma cell lines. Properties of SP cells were evaluated by their proliferative index, colony-forming efficiency and tumorigenic potential. Results Characteristic SP cells could be detected by FACS in lung adenocarcinoma cell lines. And the proportion of SP cells is greatly increased after serum-free culture.SP cells have a greater proliferative index, a higher colony-forming efficiency and a greater ability to form tumor in vivo .Conclusion SP cells exist in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.

  8. The Promyelocytic Leukemia Zinc Finger Transcription Factor Is Critical for Human Endometrial Stromal Cell Decidualization.

    Directory of Open Access Journals (Sweden)

    Ramakrishna Kommagani

    2016-04-01

    Full Text Available Progesterone, via the progesterone receptor (PGR, is essential for endometrial stromal cell decidualization, a cellular transformation event in which stromal fibroblasts differentiate into decidual cells. Uterine decidualization supports embryo implantation and placentation as well as subsequent events, which together ensure a successful pregnancy. Accordingly, impaired decidualization results not only in implantation failure or early fetal miscarriage, but also may lead to potential adverse outcomes in all three pregnancy trimesters. Transcriptional reprogramming on a genome-wide scale underlies progesterone dependent decidualization of the human endometrial stromal cell (hESC. However, identification of the functionally essential signals encoded by these global transcriptional changes remains incomplete. Importantly, this knowledge-gap undercuts future efforts to improve diagnosis and treatment of implantation failure based on a dysfunctional endometrium. By integrating genome-wide datasets derived from decidualization of hESCs in culture, we reveal that the promyelocytic leukemia zinc finger (PLZF transcription factor is rapidly induced by progesterone and that this induction is indispensable for progesterone-dependent decidualization. Chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq identified at least ten progesterone response elements within the PLZF gene, indicating that PLZF may act as a direct target of PGR signaling. The spatiotemporal expression profile for PLZF in both the human and mouse endometrium offers further support for stromal PLZF as a mediator of the progesterone decidual signal. To identify functional targets of PLZF, integration of PLZF ChIP-Seq and RNA Pol II RNA-Seq datasets revealed that the early growth response 1 (EGR1 transcription factor is a PLZF target for which its level of expression must be reduced to enable progesterone dependent hESC decidualization. Apart from furnishing

  9. Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Wang Jianing

    2011-05-01

    Full Text Available Abstract Background The human coagulation trigger tissue factor (TF is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. Methods The specific small interfering RNA (siRNA designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. Results TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. Conclusions Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways.

  10. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    Science.gov (United States)

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

  11. Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors

    NARCIS (Netherlands)

    A.M. Friel (Anne M.); L. Zhang (Ling); C.A. Pru (Cindy A.); N.C. Clark (Nicole C.); M.L. McCallum (Melissa L.); L.J. Blok (Leen); T. Shioda (Toshi); J.J. Peluso (John J.); B.R. Rueda (Bo R.); J.K. Pru (James K.)

    2015-01-01

    textabstractEndometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer

  12. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K;

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis...

  13. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    Science.gov (United States)

    2016-11-14

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  14. Differentiation of human menstrual blood-derived endometrial mesenchymal stem cells into oocyte-like cells.

    Science.gov (United States)

    Lai, Dongmei; Guo, Ying; Zhang, Qiuwan; Chen, Yifei; Xiang, Charlie

    2016-11-01

    Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a unique stem cell source. Evidence suggests that EnSCs exhibit a multi-lineage potential and have attracted extensive attention in regenerative medicine. However, the potential of EnSCs to differentiate into germline cells in vitro remains unclear. In this study, EnSCs were induced to differentiate into germ cells in a differentiation medium supplemented with 20% human follicular fluid. Our results demonstrated that EnSCs derived from human menstrual blood form oocyte-like cells and express germ cell markers. The induced cell aggregates contained not only oocyte-like structures but also cells expressing follicle stimulating hormone receptor and luteotropic hormone receptor, and produced estrogen and progesterone regulated by gonodatropin, suggesting that granulosa-like and theca-like cells were also induced. We further found that granulosa cells promote the development of oocyte-like cells and activate the induction of blastocyst-like structures derived from EnSCs. In conclusion, EnSCs may potentially represent an in vitro system for the investigation of human folliculogenesis.

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

    Science.gov (United States)

    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.

  16. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

    Directory of Open Access Journals (Sweden)

    Devic Ana

    2015-12-01

    Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.

  17. Empirical studies about quercetin increasing chemosensitivity on human lung adenocarcinoma cell line A549

    Institute of Scientific and Technical Information of China (English)

    Xuejun Zhan; Runxiang Zhang; Yanping Xu; Shuhua Yang; Daze Xie; Liwei Tan

    2012-01-01

    Objective: The present study was designed to investigate whether quercetin exerts increasing chemosensitivity on human lung adenocarcinoma cells when quercetin combined with cisplatin (DDP) and vincristine (VCR) in vitro respectively and its possible antitumor mechanism. To provide experimental proof for clinical combination application. Methods: Using intermittent administration of high dose VCR, human lung adenocarcinoma sensitive cell line (A549/S) was induced to VCR-resistant human lung adenocarcinoma cell line (A549/VCR). MTT assay was adapted for examing the 50% inhibition (IC50) value of DDP and VCR on A549/S and A549/VCR when quercetin combined with DDP and VCR respectively. Results: IC50 of DDP on A549/S and A549/VCR was 10.18 and 12.35 mg/L, and the IC50 of VCR on the two cell lines was 1.21 and 12.77 mg/L, respectively. The resistance fold of A549/VCR on VCR and DDP was 10.55 and 1.21, respectively. When quercetin at concentration of 50, 100 and 200 μmol/L in combination with DDP and VCR respectively, the IC50 of DDP and VCR on A549/S and A549/VCR were obvious decreased (P < 0.05 – P < 0.01). Conclusion: The experiment results suggested that quercetin could increase the chemosensitivity and partly revise the resistance of A549/VCR.

  18. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei

    2010-03-04

    We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

  19. CHANGES OF NUCLEAR MATRIX PROTEIN AND ITS RELATIONSHIP WITH c-erbB-2 IN HUMAN COLON ADENOCARCINOMA

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-lan; GAO Jing; LI Yuan-yuan

    2005-01-01

    Objective: Nuclear matrix protein is tissue, cell-type specific, and tumor-relative. It plays an important role in the regulation of intranuclear processes. Some researches also showed that a c-erbB-2 promoter-specific DNA-binding nuclear matrix protein is present only in malignant human breast tissues and induces mitogenesis and cell surface expression of the c-erbB-2 protein in resting NIH/3T3 cells. But it is not clear that how it in colon adenocarcinomas. Methods:Two-dimensional gel electrophoretic method was used for NMP identification and immunohistochemistry was used for c-erbB-2 detection in 12 cases of colon adenocarcinomas and matched adjacent normal colon tissues. Results: 5 different nuclear matrix proteins (named C1-C5) were identified in 12 colon adenocarcinoma specimens, but not in the matched adjacent normal colon tissues; 3 nuclear matrix proteins (named N1-N3) were identified in all 12 matched adjacent normal colon tissues, but not in colon adenocarcinoma specimens. A nuclear matrix protein (named N4) was detected in all of 9moderated-well differentiated adenocarcinomas and all 12 matched adjacent normal colon tissues, but not in 3poor-differentiated adenocarcinomas. All of the 10 colon adenocarcinomas which had the nuclear matrix protein C4 were c-erbB-2 expression positive. Conclusion: The data suggest that there are specific nuclear matrix proteins in colon adenocarcinomas and its subtypes, which maybe valuable to serve as markers of colon adenocarcinomas in future. Nuclear matrix protein C4 probably is a c-erbB-2 promotor-specific nuclear matrix protein in colon adenocarcinomas, and may induce the expression of c-erbB-2.

  20. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Suping Ren

    Full Text Available Progestagen-associated endometrial protein (PAEP is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.

  1. Apposition to endometrial epithelial cells activates mouse blastocysts for implantation.

    Science.gov (United States)

    Ruane, Peter T; Berneau, Stéphane C; Koeck, Rebekka; Watts, Jessica; Kimber, Susan J; Brison, Daniel R; Westwood, Melissa; Aplin, John D

    2017-09-01

    How do interactions between blastocyst-stage embryos and endometrial epithelial cells regulate the early stages of implantation in an in vitro model? Mouse blastocyst apposition with human endometrial epithelial cells initiates trophectoderm differentiation to trophoblast, which goes on to breach the endometrial epithelium. In vitro models using mouse blastocysts and human endometrial cell lines have proven invaluable in the molecular characterisation of embryo attachment to endometrial epithelium at the onset of implantation. Genes involved in embryonic breaching of the endometrial epithelium have not been investigated in such in vitro models. This study used an established in vitro model of implantation to examine cellular and molecular interactions during blastocyst attachment to endometrial epithelial cells. Mouse blastocysts developed from embryonic day (E) 1.5 in vitro were hatched and co-cultured with confluent human endometrial adenocarcinoma-derived Ishikawa cells in serum-free medium. A scale of attachment stability based on blastocyst oscillation upon agitation was devised. Blastocysts were monitored for 48 h to establish the kinetics of implantation, and optical sectioning using fluorescence microscopy revealed attachment and invasion interfaces. Quantitative PCR was used to determine blastocyst gene expression. Data from a total of 680 mouse blastocysts are reported, with 3-6 experimental replicates. T-test and ANOVA analyses established statistical significance at P cells over the first 24 h of co-culture, with intermediate and stable attachment occurring from 28 h (E5.5 + 4 h) in a hormone-independent manner. Attached embryos fixed after 48 h (E6.5) frequently exhibited outgrowths, characterised morphologically and with antibody markers as trophoblast giant cells (TGCs), which had breached the Ishikawa cell layer. Beginning co-culture at E5.5 also resulted in intermediate and stable attachment from E5.5 + 4 h; however, these embryos did not go on to

  2. Endometrial cancer with cervical extension mimicking dual concordant endometrial and cervical malignancy by F18 FDG PET and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Seok Nam [Kwandong Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    A 35 year old woman with endometrial cancer and cervical extension underwent F18 FDG PET CT and MRI studies after resection of a cervical mass presumed to be cervical myoma. The patient underwent cervical myomectomy and the histopathologic report revealed poorly differentiated invasive carcinoma. Cervical cancer was ruled out because the patient had no history of sexual intercourse and was negative for human papilloma virus infection. The patient underwent radical hysterectomy, bilateral salpingo oophorectomy, pelvic and para aortic lymph node dissection, and multiple biopsies. F18 FDG PET CT showed intense FDG uptake along the cervix wall. T2 weighted MRI also revealed a mass lesion with high SI involving the anterior and posterior lips of the uterine cervix. Another area of focal increased uptake above the endometrial lesion in the left pelvic cavity was observed on PET CT and MRI, possibly due to a functioning ovary. PET CT and MRI were interpreted as showing a dual concordant malignant lesion due to separated FDG uptakes and high SI without any connection between the cervical and endometrial lesions. F18 FDG PET CT showed intense FDG uptake along the endometrium. Given the patient's history and the fact that she was not menstruating at the time of imaging, this intense uptake was interpreted as another pathologic lesion, suggesting dual primary lesions. A suspected heterogeneous mass lesion along the endometrium suggesting concordant endometrial cancer was found on MRI. Endometrial cancer with cervical extension is sometimes difficult to differentiate from primary cervical cancer. The final histopathologic report showed poorly differentiated endometrial adenocarcinoma with cervical extension, although the FDG PET CT and MRI findings were suggestive of concordant cervical and endometrial cancer. Although histopathologic confirmation is necessary for final diagnosis, MRI and FDG PET CT studies may aid in the differential diagnosis. A metastatic cervical mass

  3. Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.

    Directory of Open Access Journals (Sweden)

    Lorraine Lin Shuya

    Full Text Available Adequate differentiation or decidualization of endometrial stromal cells (ESC is critical for successful pregnancy in humans and rodents. Here, we investigated the role of leukemia inhibitory factor (LIF in human and murine decidualization. Ex vivo human (H ESC decidualization was induced by estrogen (E, 10(-8 M plus medroxyprogesterone acetate (MPA, 10(-7 M. Exogenous LIF (≥50 ng/ml induced STAT3 phosphorylation in non-decidualized and decidualized HESC and enhanced E+MPA-induced decidualization (measured by PRL secretion, P100 pg/mg G-CSF, IL6, IL8, and MCP1. Decidualized HESC secreted IL6, IL8, IL15 and MCP1. LIF (50 ng/ml up-regulated IL6 and IL15 (P<0.05 secretion in decidualized HESC compared to 0.5 ng/ml LIF. In murine endometrium, LIF and LIFR immunolocalized to decidualized stromal cells on day 5 of gestation (day 0 = day of plug detection. Western blotting confirmed that LIF and the LIFR were up-regulated in intra-implantation sites compared to inter-implantation sites on Day 5 of gestation. To determine the role of LIF during in vivo murine decidualization, intra-peritoneal injections of a long-acting LIF antagonist (PEGLA; 900 or 1200 µg were given just post-attachment, during the initiation of decidualization on day 4. PEGLA treatment reduced implantation site decidual area (P<0.05 and desmin staining immuno-intensity (P<0.05 compared to control on day 6 of gestation. This study demonstrated that LIF was an important regulator of decidualization in humans and mice and data provides insight into the processes underlying decidualization, which are important for understanding implantation and placentation.

  4. Glucosamine inhibits decidualization of human endometrial stromal cells and decreases litter sizes in mice.

    Science.gov (United States)

    Tsai, Jui-He; Schulte, Maureen; O'Neill, Kathleen; Chi, Maggie M-Y; Frolova, Antonina I; Moley, Kelle H

    2013-07-01

    Embryo implantation in the uterus depends on decidualization of the endometrial stromal cells (ESCs), and glucose utilization via the pentose phosphate pathway is critical in this process. We hypothesized that the amino sugar glucosamine may block the pentose phosphate pathway via inhibition of the rate-limiting enzyme glucose-6-phosphate dehydrogenase in ESCs and therefore impair decidualization and embryo implantation, thus preventing pregnancy. Both human primary and immortalized ESCs were decidualized in vitro in the presence of 0, 2.5, or 5 mM glucosamine for 9 days. Viability assays demonstrated that glucosamine was well tolerated by human ESCs. Exposure of human ESCs to glucosamine resulted in significant decreases in the activity and expression of glucose-6-phosphate dehydrogenase and in the mRNA expression of the decidual markers prolactin, somatostatin, interleukin-15, and left-right determination factor 2. In mouse ESCs, expression of the decidual marker Prp decreased upon addition of glucosamine. In comparison with control mice, glucosamine-treated mice showed weak artificial deciduoma formation along the stimulated uterine horn. In a complementary in vivo experiment, a 60-day-release glucosamine (15, 150, or 1500 μg) or placebo pellet was implanted in a single uterine horn of mice. Mice with a glucosamine pellet delivered fewer live pups per litter than those with a control pellet, and pup number returned to normal after the end of the pellet-active period. In conclusion, glucosamine is a nonhormonal inhibitor of decidualization of both human and mouse ESCs and of pregnancy in mice. Our data indicate the potential for development of glucosamine as a novel, reversible, nonhormonal contraceptive.

  5. CLONING AND IDENTIFICATION OF A GENE RELATED TO THE DIFFERENTIATION OF HUMAN GASTRIC ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    王建华; 陈诗书

    2002-01-01

    Objective: To compare the differential expression of mRNA between MKN-28 (highly differentiated) and MKN-45 (poorly differentiated) gastric adenocarcinoma cells and identify genes involved in human gastric adenocarcinoma differentiation. Methods: Differential expression of mRNA between MKN-28 and MKN-45 adenocarcinoma cells was investigated by fluorescent differential display (FDD). Differentially expressed cDNA was analyzed by bio-informatics and confirmed by RT-PCR and Northern-blot. Results: 45 differential fragments were finally attained. One of them (No. 10) was an approximate 750 bp cDNA and highly up-regulated in MKN-45 cells as compared with MKN-28 cells. By using Blastn and UniGene database analysis, we found the fragment was mapped to chromosome 14q11.2(q12 and showed a significant homology to Bcl-2 binding protein gene (BNip3), which was recently identified encoding pro-apoptosis protein located in mitochondrial. Conclusion: The BNip3 induced apoptosis could be suppressed by interacting with bcl-2. The BNip3 gene in tumor cells might be up-regulated by the hypoxia response element through the HIF1a transcription factor, causing death of the hypoxic cells at the center of the tumor where vascularization is usually poor in the process of tumor development.

  6. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets.

    Directory of Open Access Journals (Sweden)

    Jinju Wang

    Full Text Available Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs. The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs. In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29 and negative hematopoietic stem cell markers (CD45 and CD34 expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin (TPO for 18 days. The MK differentiation was analyzed by flow cytometry and confocal microscopy. The differentiation medium was collected for PLT production analysis by flow cytometry, transmission electron microscopy and functional measurements. Our results show: 1 MKs were successfully generated from hESSCs as identified by expression of specific markers (CD41a: 1 ± 0.09% and 39 ± 3.0%; CD42b: 1.2 ± 0.06% and 28 ± 2.0%, control vs. differentiation accompanied with reduction of pluripotent transcription factors (Oct4 and Sox2 expression; 2 The level of PLTs in the differentiation medium was 16 ± 1 number/µl as determined by size (2-4 µm and CD41a expression (CD41a: 1 ± 0.4% and 90±2.0%, control vs. differentiation; 3 Generated PLTs were functional as evidenced by the up-regulation of CD62p expression and fibrinogen binding following thrombin stimulation; 4 Released PLTs showed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system as PLTs from peripheral blood determined by electron microscopic analysis. Data demonstrate the feasibility of generating MKs from hESSCs, and that the generated MKs release functional PLTs. Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT production.

  7. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets.

    Science.gov (United States)

    Wang, Jinju; Chen, Shuzhen; Zhang, Cheng; Stegeman, Samantha; Pfaff-Amesse, Teresa; Zhang, Ying; Zhang, Wenfeng; Amesse, Lawrence; Chen, Yanfang

    2012-01-01

    Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin (TPO) for 18 days. The MK differentiation was analyzed by flow cytometry and confocal microscopy. The differentiation medium was collected for PLT production analysis by flow cytometry, transmission electron microscopy and functional measurements. Our results show: 1) MKs were successfully generated from hESSCs as identified by expression of specific markers (CD41a: 1 ± 0.09% and 39 ± 3.0%; CD42b: 1.2 ± 0.06% and 28 ± 2.0%, control vs. differentiation) accompanied with reduction of pluripotent transcription factors (Oct4 and Sox2) expression; 2) The level of PLTs in the differentiation medium was 16 ± 1 number/µl as determined by size (2-4 µm) and CD41a expression (CD41a: 1 ± 0.4% and 90±2.0%, control vs. differentiation); 3) Generated PLTs were functional as evidenced by the up-regulation of CD62p expression and fibrinogen binding following thrombin stimulation; 4) Released PLTs showed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system) as PLTs from peripheral blood determined by electron microscopic analysis. Data demonstrate the feasibility of generating MKs from hESSCs, and that the generated MKs release functional PLTs. Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT production.

  8. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma.

    Science.gov (United States)

    Gupta, S; Srivastava, M; Ahmad, N; Bostwick, D G; Mukhtar, H

    2000-01-01

    Aberrant or increased expression of cyclooxygenase (COX)-2 has been implicated in the pathogenesis of many diseases including carcinogenesis. COX-2 has been shown to be over-expressed in some human cancers. Employing semi-quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry we assessed COX-2 expression in samples of pair-matched benign and cancer tissue obtained from the same prostate cancer patient. Mean levels of COX-2 mRNA were 3.4-fold higher in prostate cancer tissue (n = 12) compared with the paired benign tissue. The immunoblot analysis demonstrated that as compared to benign tissue COX-2 protein was over-expressed in 10 of 12 samples examined. Immunohistochemical analysis also verified COX-2 over-expression in cancer than in benign tissue. To our knowledge, this is the first in vivo study showing an over-expression of COX-2 in prostate cancer. These data suggest that COX-2 inhibitors may be useful for prevention or therapy of prostate cancer in humans.

  9. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma

    Science.gov (United States)

    Yu, Wendan; Li, Jinxiu; Tang, Zhipeng; Yu, Zhenlong; Zhao, Lei; Zhang, Yixiang; Wang, Ziyi; Wang, Peng; Li, Yechi; Li, Fengzhou; Sun, Zhe; Xuan, Yang; Tang, Ranran; Deng, Wu-guo; Guo, Wei; Gu, Chundong

    2016-01-01

    Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma. PMID:27384875

  10. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  11. Effects of Tibolone Metabolites on Human Endometrial Cell Lines in Co-Culture

    Science.gov (United States)

    Barbier, Claire; Kloosterboer, Helenius J.; Kaufman, David G.

    2010-01-01

    In human endometrium, cell proliferation is regulated by ovarian steroids through heterotypic interactions between stromal and epithelial cells populating this tissue. We tested the proliferative effects of tibolone and its metabolites using endometrial co-cultures that mimic the normal proliferative response to hormones. We found that both the Δ4-tibolone metabolite and the pure progestin ORG2058 counteract estradiol-driven epithelial cell proliferation. Surprisingly, the estrogen receptor binding 3-hydroxyl-metabolites of tibolone also counteracted estradiol-driven proliferation. Inhibition of proliferation by 3β-OH-tibolone was abrogated by low doses of the progesterone receptor antagonist mifepristone, This suggests that 3β-OH-tibolone is converted to a progestagenic metabolite. We found that the stromal cells used in the co-cultures express high levels of the ketosteroid dehydrogenase, AKR1C2, which is able to oxidize 3β-OH-tibolone back to tibolone. Thus the unexpected progestagenic effect of 3β-OH-tibolone in these co-cultures may be due to metabolic activity present in the stromal cells of the co-cultures. PMID:18212357

  12. Distribution volumes of macromolecules in human ovarian and endometrial cancers--effects of extracellular matrix structure.

    Science.gov (United States)

    Haslene-Hox, Hanne; Oveland, Eystein; Woie, Kathrine; Salvesen, Helga B; Tenstad, Olav; Wiig, Helge

    2015-01-01

    Elements of the extracellular matrix (ECM), notably collagen and glucosaminoglycans, will restrict part of the space available for soluble macromolecules simply because the molecules cannot occupy the same space. This phenomenon may influence macromolecular drug uptake. To study the influence of steric and charge effects of the ECM on the distribution volumes of macromolecules in human healthy and malignant gynecologic tissues we used as probes 15 abundant plasma proteins quantified by high-resolution mass spectrometry. The available distribution volume (VA) of albumin was increased in ovarian carcinoma compared with healthy ovarian tissue. Furthermore, VA of plasma proteins between 40 and 190 kDa decreased with size for endometrial carcinoma and healthy ovarian tissue, but was independent of molecular weight for the ovarian carcinomas. An effect of charge on distribution volume was only found in healthy ovaries, which had lower hydration and high collagen content, indicating that a condensed interstitium increases the influence of negative charges. A number of earlier suggested biomarker candidates were detected in increased amounts in malignant tissue, e.g., stathmin and spindlin-1, showing that interstitial fluid, even when unfractionated, can be a valuable source for tissue-specific proteins. We demonstrate that the distribution of abundant plasma proteins in the interstitium can be elucidated by mass spectrometry methods and depends markedly on hydration and ECM structure. Our data can be used in modeling of drug uptake, and give indications on ECM components to be targeted to increase the uptake of macromolecular substances.

  13. Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma.

    Science.gov (United States)

    Singh, Mohan; Harris-Birtill, David C C; Zhou, Yu; Gallina, Maria E; Cass, Anthony E G; Hanna, George B; Elson, Daniel S

    2016-03-01

    Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre-determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 x 10(10) GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 degrees C was observed in tissues incubated with GNRs, whereas only a modest 2 degrees C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs.

  14. FOXP1 forkhead transcription factor is associated with the pathogenesis of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Makito Mizunuma

    2016-05-01

    Full Text Available Endometrial cancers are mostly estrogen-dependent. FOXP1 is a P subfamily of forkhead box (FOX, and known as an estrogen-responsive transcription factor. The aims of this study were to examine histological location of FOXP1 in normal and malignant endometrium, and to investigate a possible association between FOXP1 and other factors considered to be involved in pathogenesis of endometrial cancer. The levels of FOXP1, estrogen receptor (ERα, and ERβ expression were examined immunohistochemically in normal and malignant endometrium obtained from 75 women (8 normal, 8 atypical endometrial hyperplasia, and 59 endometrial cancers from grade 1 to 3. The effects of estrogen on ERα, FOXP1, KRAS, and PTEN expression were analyzed in telomerase-immortalized human endometrial stromal cells (T HESCs by Western blotting. Western blotting was also used to examine the effect of FOXP1 plasmid DNA or siRNA transfection on KRAS and PTEN expression in Ishikawa cells (well differentiated endometrioid adenocarcinoma, HEC-50B cells (poorly differentiated endometrioid adenocarcinoma, and T HESCs, respectively. FOXP1 was expressed in normal and malignant endometrium, but the rate of expression was different depending upon menstrual cycle and pathological grade of malignancy. FOXP1 expression in nucleus and cytoplasm of grade 3 endometrioid cancers was significantly lower than that of grade 1 and 2 ones. Estradiol increased levels of FOXP1 and KRAS expression in a dose- and time-dependent manner in T HESCs cells, and FOXP1 transfection or knockdown led to increase or decrease of KRAS expression but not PTEN. KRAS expression level was significantly related to FOXP1 and ERα levels in cancer tissues. Estradiol did not affect KRAS expression in T HESCs cells transfected with FOXP1 siRNA. These results suggest that FOXP1 is involved in estrogen dependent endometrial cancers through KRAS pathway.

  15. Low dose rate vaginal brachytherapy of endometrial adenocarcinomas; Curietherapie vaginale postoperatoire des adenocarcinomes de l`endometre a bas debit de dose

    Energy Technology Data Exchange (ETDEWEB)

    Charra-Brumaud, C.; Peiffert, D.; Hoffstetter, S.; Luporsi, E.; Guillemin, F.; Bey, P. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France)

    1998-01-01

    Surgery is the primary treatment for endometrial carcinoma. Methods of complementary treatment are still debated, with the potential association of external radiotherapy and/or brachytherapy before or after surgery. This study was aimed at evaluating local control and complication rates in a series of patients treated by hysterectomy followed by postoperative vaginal low-dose rate brachytherapy (BT) combined with pelvic irradiation in case of poor prognosis factors. From 1978 to 1993, 101 patients were treated at the Centre Alexis-Vautrin, France according to this scheme. Forty five had deep myometrial invasion, and thirteen cervical involvement. Fifty patients received pelvic irradiation (median dose 46 Gy) combined with BT (dose 14 Gy, median volume 127 cm{sup 3}); 51 patients had BT alone (dose 60 Gy, median volume 71 cm{sup 3}). The 5-year overall survival rate was 83 % and the local control rate 97 % with a median follow-up of 7 years. Multivariate analysis showed two factors of bad prognosis, i.e. deep myometrial invasion and cervical involvement. Three severe complications occurred in two patients for whom the treated volume was larger than the theoretical target volume. Eleven patients developed metastases. Results obtained from this series are comparable with those of previous studies, particularly in regard to pre-operative BT. The complication rate is also satisfactory and depends on the irradiation precision and the definition of the target volume. (authors)

  16. Transcription Activity of Ectogenic Human Carcinoembryonic Antigen Promoter in Lung Adenocarcinoma Cells A549

    Institute of Scientific and Technical Information of China (English)

    XIONG Weining; FANG Huijuan; XU Yongjian; XIONG Shendao; CAO Yong; SONG Qingfeng; ZENG Daxiong; ZHANG Huilan

    2006-01-01

    The transcription activity of ectogenic human carcinoembryonic antigen (CEA) promoter in lung adenocarcinoma cells A549 was investigated for the further gene-targeting therapy. The reporter gene green fluorescent protein (GFP) driven by CEA promoter and human cytomegalovirus (CMV) promoter were relatively constructed and named plasmid pCEA-EGFP and pCMV-GFP respectively. The intensity of fluorescence was detected by fluorescence microscope and flow cytometry analysis after the pCEA-GFP and pSNAV-GFP plasmids were transfected into A549 cells through liposome respectively. The results showed (4.08±0.63) % of the A549 cells transfected with pCEA-AFP plasmid expressed, significantly lower than that of the A549 cells transfected with pCMV-GFP [(43.27±3.54) %]. It was suggested that ectogenic human CEA promoter in lung adenocarcinoma cells A549 was weakly expressed. The distinct specificity of CEA promoter in CEA high expression cells was regarded as a tool in selective gene therapy, but the transcription activity of ectogenic human CEA promoter was needed to increase in the future.

  17. Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7901 in vitro

    Institute of Scientific and Technical Information of China (English)

    Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du

    2004-01-01

    AIM: To explore the effects of mifepristone, a progesterone receptor (PR) antagonist, on the proliferation of human gastric adenocarcinoma cell line SGC-7 901 in vitro and the possible mechanisms involved.METHODS: In situ hybridization was used to detect theexpression of PR mRNA in SGC-7 901 cells. After treatment with various concentrations of mifepristone (2.5, 5, 10,20 μmol/L) at various time intervals, the ultrastructural changes, cell proliferation, cell-cycle phase distribution, and the expression of caspase-3 and Bcl-XL were analyzed using transmission electron microscopy (TEM), tetrazolium blue(MTT) assay, 3H-TdR incorporation, flow cytometry, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Mifepristone markedly induced apoptosis and inhibited cell proliferation of PR- positive SGC-7 901 cells revealed by TEM, MTT assay and 3H-TdR incorporation, in a dose- and time-dependent manner. The inhibitory rate was increased from 8.98% to 51.29%. Flow cytometric analysis showed mifepristone dose-dependently decreased cells in S and G2/M phases, increased cells in Go/G1 phase,reduced the proliferative index from 57.75% to 22.83%. In addition, mifepristone up-regulated the expression of caspase-3, and down- regulated the Bcl-XL expression, dose-dependently.CONCLUSION: Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7 901 in vitro through multiple mechanisms, and may be a beneficial agent against human adenocarcinoma.

  18. Expression of immunohistochemical markers in diagnosis of endometrial adenocarcinoma and cervical adenocarcinoma and its clinical significance%免疫组化标记物在子宫内膜样腺癌与宫颈腺癌诊断中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    黄敬皓

    2015-01-01

    item combined detection of Vim ,CEA ,ER and P16 protein .Results The positive rates of Vim and ER in the group A were 71 .25% and 73 .75% respectively ,which were higher than those in the group B ,the differences were statistically significant (P<0 .05) .The positive rates of CEA and P16 protein in the group B were 73 .75% and 67 .50% respectively ,which were higher than those in the group A ,the differences were statistically sig‐nificant (P<0 .05) .The specificity ,sensitivity and accuracy of the 4‐item combined detection in the group A and B were 92 .43% and 98 .62% ,56 .44% and 58 .57% ,71 .21% and 74 .62% respectively ,which were higher than those of the 3‐item combined detection in the same group ,the differences were statistically significant (P<0 .05) .Conclu‐sion Vim and ER have high positive expression in endometrial adenocarcinoma tissue ,while CEA and P16 have high positive expression in cervical adenocarcinoma .p16 protein combined with traditional triple combination detection could improve the differential diagnostic accuracy of endometrial adenocarcinoma and cervical adenocarcinoma .

  19. Three-dimensional cultures of human endometrial cells on Matrigel mimic in vivo morphology

    Institute of Scientific and Technical Information of China (English)

    ZHU Hai-yan; WANG Jun-xia; TONG Xiao-mei; XU Wei-hai; JIANG Ling-ying; JING Xiao-ying; YANG Ling-yun; ZHOU Feng; ZHANG Song-ying

    2012-01-01

    Background The regulation of endometrial physiology and morphogenesis by the paracrine effectors has been well established using in vivo studies.A more complete understanding of the endometrial function has been delayed due,in part,to a lack of appropriate culture models.In this study,we aimed to simulate the in vivo three-dimensional (3-D) growth pattern of endometrial cells using a 3-D in vitro culture system.Methods Isolated endometrial epithelial cells,stromal cells and RL95-2 cells were seeded into culture chambers coated with the extracellular matrix Matrigel and observed using light microscopy.Fluorescence staining and immunohistochemistry were used to assess the morphology.Results Depending on the culture conditions,epithelial cells and RL95-2 cells formed multicellular structures on Matrigel; stromal cells remained individually distinguishable or grew together to form 3-D lattice-like structures.Conclusions Matrigel provided a good microenvironment for culturing endometrial cells.The cells cultured in the Matrigel-coated chambers closely resembled those seen in vivo.

  20. Expression of {beta}{sub 1} integrins in human endometrial stromal and decidual cells

    Energy Technology Data Exchange (ETDEWEB)

    Shiokawa, Shigetatsu; Yoshimura, Yasunori; Nakamura, Yukio [Kyorin Univ. School of Medicine, Tokyo (Japan)] [and others

    1996-04-01

    The present study was undertaken to investigate the expression of {beta}{sub 1} integrins in human endometrium and decidua using flow cytometry, immunohistochemistry, and immunoprecipitation. Fluorescence-activated flow cytometry demonstrated the greater expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, and {alpha}{sub 5} subunits of the {beta}{sub 1} integrin family in cultured stromal cells from the midsecretory phase, than in those of the early proliferative phase. The addition of estradiol (E{sub 2}) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of {beta}{sub 1} integrins in vitro. Flow cytometry also demonstrated the expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, {alpha}{sub 3}, {alpha}{sub 5}, and {alpha}{sub 6} subunits of {beta}{sub 1} integrin family in cultured decidual cells, and the enriched-fraction of prolactin (PRL)-producing decidual cells isolated by Percoll gradients showed high levels of {beta}{sub 1} integrins expression. Immunohistochemistry confirmed the {beta}{sub 1} integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In summary, the present study demonstrated that endometrial stromal and decidual cells expressed {beta}{sub 1} integrin subunits at their surfaces. The expression exhibited a variability throughout the menstrual cycles, being predominantly detected in the secretory phase, and was maintained highly in the decidua. Thus, {beta}{sub 1} integrins in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation. 43 refs., 7 figs., 2 tabs.

  1. Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo.

    Science.gov (United States)

    Cai, Yuchen; Xia, Qing; Luo, Rongzhen; Huang, Peiyu; Sun, Yueli; Shi, Yanxia; Jiang, Wenqi

    2014-01-01

    Berberine is an alkaloid isolated from the Chinese herbal medicine Huanglian, and has long been used as an antibiotic. Its antineoplastic properties were subsequently discovered in vitro. The purpose of this study was to investigate the effects of berberine on the growth of human colorectal carcinoma cells in vitro and in vivo. The results showed that berberine inhibited human colorectal adenocarcinoma (LoVo) cell growth in a time- and dose-dependent manner. A WST-1 assay showed that the IC50 value after 72 h was 40.79 ± 4.11 μM. Cell cycle analysis of 40 μM berberine-treated LoVo cells by flow cytometry showed accumulation of cells in the G2/M phase. The inhibition of LoVo cell growth by berberine was associated with the suppression of cyclin B1, cdc2, and cdc25c proteins. Berberine at a dose of 50 mg kg(-1) day(-1) showed inhibitory rates of 45.3% in a human colorectal adenocarcinoma xenograft in nude mice. The combination of berberine and 5-fluorouracil (5-FU) had a higher inhibitory rate (59.8%) than the berberine group (36.4%, P = 0.01), but no significant difference was observed between the 5-FU group (43.0%, P = 0.06) and the combination group. These results support the possibility that berberine may be useful as an alternative therapy for colorectal carcinoma.

  2. Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM

    Institute of Scientific and Technical Information of China (English)

    Yong-Wu Li; Lin Bai; Lyu-Xia Dai; Xu He; Xian-Ping Zhou

    2016-01-01

    Background: Lung cancer has become the leading cause of death in many regions.Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes.The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM.Methods: We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations.In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR).Results: We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19.Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations.CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33 and 17p 13.1-13.3.And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG).Conclusions: The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis.We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33, and 17p 13.1-13.3.Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.

  3. Leptin upregulates beta3-integrin expression and interleukin-1beta, upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures.

    Science.gov (United States)

    Gonzalez, R R; Leavis, P

    2001-10-01

    Human endometrium and endometrial epithelial cells (EECs) either cultured alone or cocultured with human embryos express leptin and leptin receptor. This study compares the effect of leptin with that of interleukin-1beta (IL-1beta) on the expression of beta3-EEC integrin, a marker of endometrial receptivity. Both cytokines increased the expression of beta3-EEC at concentrations in the range of 0.06-3 nM; however, leptin exhibited a significantly greater effect than IL-1beta. We also determined the regulatory effects of IL-1beta on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal cell (ESC) cultures. In EEC cultures, IL-1beta upregulated secretion of leptin and expression of both leptin and leptin receptors. No effect of IL-1beta was found in the ESC cultures. However, leptin exhibited marginal upregulation of leptin receptor. The upregulation of beta3-integrin and leptin/leptin receptor expression by IL-1beta in EEC cultures indicates that both cytokines may be implicated in embryonic-maternal cross-talk during the early phase of human implantation. Our present data also raise the possibility that leptin is an endometrial molecular effector of IL-1beta action on beta3-integrin upregulation. Thus, a new role for leptin in human reproduction as an autocrine/paracrine regulator of endometrial receptivity is proposed.

  4. Human epidermal growth factor receptor-2 overexpression and amplification in metastatic and recurrent high grade or type 2 endometrial carcinomas

    Directory of Open Access Journals (Sweden)

    Kato R

    2013-08-01

    Full Text Available Rina Kato,1 Kiyoshi Hasegawa,1 Risa Ishii,1 Akiko Owaki,1 Yutaka Torii,1 Shuko Oe,1 Hiroshi Hirasawa,2 Yoichi Kobayashi,3 Yasuhiro Udagawa1 1Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan; 2Department of Pathology, Fujita Health University School of Medicine, Toyoake, Japan; 3Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Japan Introduction: Human epidermal growth factor receptor (HER-2 overexpression or gene amplification is more common in high-grade or type 2 endometrial carcinomas. We assessed the discordance of HER-2 expression between primary and metastatic or recurrent endometrial carcinomas. Materials and methods: Thirty-six primary, along with 14 metastatic and five recurrent tumors (matched to primaries, pathologically confirmed as high-grade or type 2 endometrial carcinomas, were submitted for immunohistochemistry (IHC for HER-2. Fluorescence in situ hybridization was performed when the tumors showed HER-2 overexpression (≥2+ IHC score. The results of the IHC and fluorescence in situ hybridization assays were compared between the primary and metastatic or recurrent tumors. The relationships between HER-2 expression and clinicopathological factors or prognosis were investigated. Results: HER-2 overexpression and HER-2 amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies ≥2.2 were detected in 33.3% (twelve of 36 patients and 5.6% (two of 36 patients of primary tumors, respectively. HER-2 overexpression was not associated with clinicopathological factors or prognosis. In 19 tumor specimens obtained from metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were detected in 57.9% (eleven patients and 15.8% (three patients, respectively. HER-2 overexpression tended to predict a worse prognosis. Conclusion: HER-2 expression in metastatic or recurrent tumors was more frequent than in matched primary high

  5. P16 and retinoblastoma protein expression in endometrial carcinoma and clinical significance.

    Science.gov (United States)

    Koh, V Mue; Shi, Y X; Tang, Q H

    2011-01-01

    To investigate the clinical significance of p16 expression, a product of the cyclin dependent kinase inhibitor CDKN2 (also known as MTS1, multiple tumor suppressor 1) and assess its relationship with retinoblastoma protein expression in the pathogenesis of endometrial cancer. p16 and pRb expression were histochemically evaluated, using p16 and RB polyclonal antibodies on paraffin sections of 27 primary endometrial adenocarcinomas with no therapy prior to surgery, through the streptavidin peroxydase conjugated method. Further analyses were carried out using the polymerase chain reaction for exon 1 gene amplification to investigate the mechanism of abnormal p16 expression. p16 expression was detected in 100% of normal endometriums and in 74.04% of endometrial carcinomas (p p16 expression revealed four homozygous deletions. Additionally, the inverse correlation between RB and p16 expression was confirmed in this study, with 71.42% of tumors demonstrating inverse expression of p16 and RB (p p16 expression decrease is a significant event in endometrial carcinoma pathogenesis, and it is inversely correlated to tumor cell grade. Exon 1 homozygous deletion might be one of the mechanisms of loss of p16 expression. The p16/pRb growth suppressor pathway is targeted in human endometrial carcinoma.

  6. Endometrial metaplasias and reactive changes: a spectrum of altered differentiation.

    Science.gov (United States)

    Nicolae, Alina; Preda, Ovidiu; Nogales, Francisco F

    2011-02-01

    Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2, PAX2 and p16(INK4A). Complex CTM is likely to be a precursor of ciliated endometrioid-type carcinomas. MMs should be evaluated architecturally, taking into account that their atypicality is minimal. The differentiation between complex MM and mucinous carcinoma may be extremely difficult. Surface complex, papillary MM in endometrial polyps can be considered as benign. Intestinal-type endometrial MM is rare and its presence should prompt further investigation of associated lesions in the endocervix. Endometrial squamous metaplasia (ESS) is often linked to chronic irritative situations. It should be differentiated from secondary involvement by a human papilomavirus-related cervical lesion. Morular metaplasia is a mutational phenomenon with a distinct phenotype that helps to differentiate it from ESS. Morules are benign, hormonally inert structures that are often markers of complex endometrioid glandular architecture, and they are associated with an attenuated malignancy. Endometrial reactive changes are commonly associated with desquamation or hormonal imbalance. The frequent, p16(INK4A) positive, benign surface papillary syncytial change may be misdiagnosed, in some cases, as

  7. Expression of Interleukin-11 and Interleukin-11 receptor in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

    Institute of Scientific and Technical Information of China (English)

    Kazuyuki Yamazumi; Toshiyuki Nakayama; Takafumi Kusaba; Chun Yang Wen; Ayumi Yoshizaki; Yuichi Yakata; Takeshi Nagayasu; Ichiro Sekine

    2006-01-01

    AIM: There is strong evidence that interleukin-11 (IL-11)is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma.METHODS: To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting.RESULTS: Among 115 cases of adenocarcinoma, 100cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%)were positive for the IL-11Rα. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Rα, respectively. The expression of IL-11Rα correlated with the histological differentiation (P =0.033503), the depth of tumor invasion (P= 0.006395),Dukes classification (P= 0.015648) and lymphatic invasion (P=0.003865). However, the expression of IL-11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rαproteins.CONCLUSION: IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors.These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.

  8. Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose systematic administration

    Indian Academy of Sciences (India)

    Yan Shan; Chunting Wang; Li Yang; Li Juan Chen; Hong Xin Deng; Han Shuo Yang; Zhimian Li; Zhiyong Li; Li Pan; Fei Leng; Yuquan Wei

    2010-06-01

    Anti-apoptosis plays an important role in tumour formation and development. Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a target for anti-cancer drug exploitation was replaced as development. We investigated the role of the homo dominant-negative mutant Survivin-T34A in suppressing human lung adenocarcinomas (A549). The anti-tumour activity of HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing A549 subcutaneous tumours. Low-dose systemic administration was continuously used. The HSurvivinT34A plasmid (5 g/one) complexed with a cationic liposome (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed microvessel density degradation by CD31 immunohistochemistry and apoptotic cell increase by TUNEL assay, PI staining and flow cytometric analysis in the treated group. The present findings suggest that the HSurvivinT34A plasmid complexed with a cationic liposome may provide an effective approach to inhibit the growth of human lung adenocarcinomas in vitro and in vivo.

  9. A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells.

    Science.gov (United States)

    Gonzalez, Ruben Rene; Leavis, Paul C

    2003-07-01

    In this article we show that rabbit endometrial cells express leptin receptor and that human leptin triggers phosphorylation of signal transducer and activator of transcription 3 and up-regulates the expression of interleukin- 1 receptor type I as was previously found in human endometrial cells. Interestingly, leptin also upregulates the secretion of leukemia inhibitory factor and expression of its receptor by rabbit endometrial cells. Analysis of a structural model of the leptin-leptin receptor complex suggested that helices I and III of the human leptin structure were likely sites of interaction with the cytokine binding domain of leptin receptor. Accordingly, we synthesized a peptide (LPA-2) comprising helix III (residues 70-95) and investigated its ability to inhibit leptin receptor function. The effects of LPA-2 were assayed in rabbit endometrial cells, and an antileptin receptor antibody and a scrambled version of LPA-2 were used as positive and negative controls, respectively. LPA-2 binds specifically and with high affinity (Ki ~ 0.6 x 10-10 M) to leptin receptor and is a potent inhibitor of its functions in rabbit endometrial cells. Because leukemia inhibitory factor and interleukin- 1 have been implicated in embryo implantation, our results raise the possibility that the LPA-2-induced inhibition of leptin receptor may be exploited to study the actions of leptin in endometrium and in other tissues under conditions characterized by abnormal leptin production.

  10. Oleanolic acid-induced apoptosis and its relation with intracellular calcium in human lung adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    Asmitanand; Thakur

    2010-01-01

    Objective To investigate the effect of oleanolic acid (OA) on apoptosis,correlation between apoptosis and intracellular calcium,and its mechanism in human lung adenocarcinoma cell line A549. Methods Human lung adenocarcinoma A549 cells were incubated in vitro and assigned with OA concentrations of 0,10,20 and 40μg/mL. The apoptosis status of A549 cell line was detected with Annexin V-FITC/PI by flow cytometry (FCM); fluorescence intensity (FI) of A549 cells was assessed and the level of intracellular calciu...

  11. Endometrial cancer

    Science.gov (United States)

    ... to be at a higher risk of endometrial cancer: Colon or breast cancer Diabetes Gallbladder disease High blood ... laparoscopic - discharge Hysterectomy - vaginal - discharge Pelvic radiation - discharge Review Date 4/5/2016 Updated by: Irina Burd, ...

  12. Endometrial biopsy

    Science.gov (United States)

    ... chap 10. Read More Cancer Endometrial cancer Endometritis Infertility Menopause Uterine fibroids Vaginal bleeding - hormonal Review Date 9/26/2015 Updated by: Daniel N. Sacks MD, FACOG, obstetrics & gynecology in private practice, West Palm Beach, FL. Review ...

  13. [Immunomorphologic features of epithelial-stromal relationships at hyperplasia and endometrial carcinoma].

    Science.gov (United States)

    Bantysh, B B; Paukov, v S; Kogan, E A

    2012-01-01

    The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

  14. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    Directory of Open Access Journals (Sweden)

    Qiansheng Huang

    2016-03-01

    Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

  15. Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway

    Directory of Open Access Journals (Sweden)

    Wang H

    2015-08-01

    Full Text Available Huan Wang,1–3 Zhengyun Liu,4 Ying Gou,3 Yu Qin,4 Yaze Xu,5 Jie Liu,4 Jin-Zhu Wu6 1Research Center for Medicine and Biology, 2Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, 3Department of Microbiology, 4Key Lab for Basic Pharmacology of Ministry of Education, 5Pharmacy School, Zunyi Medical College, Zunyi, 6Department of Chemistry, School of Science, Harbin Institute of Technology, Harbin, People’s Republic of China Abstract: Realgar (AS4S4 has been used in traditional medicines for malignancy, but the poor water solubility is still a major hindrance to its clinical use. Realgar quantum dots (RQDs were therefore synthesized with improved water solubility and bioavailability. Human endometrial cancer JEC cells were exposed to various concentrations of RQDs to evaluate their anticancer effects and to explore mechanisms by the MTT assay, transmission electron microscopy (TEM, flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR and Western blot analysis. Results revealed that the highest photoluminescence quantum yield of the prepared RQDs was up to approximately 70%, with the average size of 5.48 nm. RQDs induced antiproliferative activity against JEC cells in a concentration-dependent manner. In light microscopy and TEM examinations, RQDs induced vacuolization and endoplasmic reticulum (ER dilation in JEC cells in a concentration-dependent manner. ER stress by RQDs were further confirmed by increased expression of GADD153 and GRP78 at both mRNA and protein levels. ER stress further led to JEC cell apoptosis and necrosis, as evidenced by flow cytometry and mitochondrial membrane potential detection. Our findings demonstrated that the newly synthesized RQDs were effective against human endometrial cancer cells. The underlying mechanism appears to be, at least partly, due to ER stress leading to apoptotic cell death and necrosis. Keywords: realgar, quantum dots

  16. RAI,one candidate gene associated with differentiation of human lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    王雪皎; 张睿; 刘芝华; 王秀琴; 丁芳; 郭明洲; 吴旻

    2000-01-01

    From all-trans retinoic acid (ATRA)-treated human lung adenocarcinoma GLC-82 cells and control, subtractive cDNA library has been constructed using subtractive hybridization technique in our laboratory. The screening of the cDNA subtractive library resulted in identification of a clone containing cDNA fragment of one ATRA-induced gene (RAI) in GLC-82 cells. The positive clone with full-length cDNA of RAI was identified by screening fetal brain cDNA library using colony hybridization technique, and then sequenced. RT-PCR results showed that RAI was expressed in many different human fetal tissues. These results suggest that RAI may be involved in cell differentiation and play an important role in vital activities of cells.

  17. RAI, one candidate gene associated with differentiation of human lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    From all-trans retinoic acid (ATRA)-treated human lung adenocarcinoma GLC-82 cells and control, subtractive cDNA library has been constructed using subtractive hybridization technique in our laboratory. The screening of the cDNA subtractive library resulted in identification of a clone containing cDNA fragment of one ATRA-induced gene (RAI) in GLC-82 cells. The positive clone with full-length cDNA of RAI was identified by screening fetal brain cDNA library using colony hybridization technique, and then sequenced. RT-PCR results showed that RAI was expressed in many different human fetal tissues. These results suggest that RAI may be involved in cell differentiation and play an important role in vital activities of cells.

  18. Antimigratory Effects of the Methanol Extract from Momordica charantia on Human Lung Adenocarcinoma CL1 Cells

    Directory of Open Access Journals (Sweden)

    Hsue-Yin Hsu

    2012-01-01

    Full Text Available Momordica charantia has been found to exhibit anticancer activity, in addition to its well-known therapeutic functions. We have demonstrated that the leaf extract of Momordica charantia (MCME induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. In this study, a different susceptibility to MCME was found in human lung adenocarcinoma CL1 cells with different metastatic ability, leading to the significant difference of cell viability and invasiveness between MCME-treated CL1-0 and CL1-5 cells. MCME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed MMP-2 and MMP-9 enzymatic activities. We proposed that MCME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt, β-catenin, and MMPs.

  19. Aqueous Extract of Solanum nigrum Leaf Activates Autophagic Cell Death and Enhances Docetaxel-Induced Cytotoxicity in Human Endometrial Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Cheng-Jeng Tai

    2012-01-01

    Full Text Available Chemotherapy is the main approach in dealing with advanced and recurrent endometrial cancer. An effective complementary ingredient can be helpful in improving the clinical outcome. Aqueous extract of Solanum nigrum leaf (AE-SN is a principal ingredient for treating cancer patients in traditional Chinese medicinal practice but lacks sufficient evidence to verify its tumor suppression efficacy. This study evaluated the antitumor effects of AE-SN and also assessed the synergistic effects of AE-SN with docetaxel On the human endometrial cancer cell lines, HEC1A, HEC1B, and KLE. The activation of apoptotic markers, caspase-3 and poly-ADP-ribose polymerase, and autophagic marker, microtubule-associated protein 1 light chain 3 A/B, wAS determined to clarify the cell death pathways responsible for AE-SN induced tumor cell death. Results indicated that AE-SN-treatment has significant cytotoxicity on the tested endometrial cancer cells with accumulation of LC3 A/B II and demonstrated a synergistic effect of AE-SN and docetaxel in HEC1A and HEC1B cells, but not KLE cells. In conclusion, AE-SN treatment was effective in suppressing endometrial cancer cells via the autophagic pathway and was also capable of enhancing the cytotoxicity of docetaxel in human endometrial cancer cells. Our results provide meaningful evidence for integrative cancer therapy in the future.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Generation of Rat Monoclonal Antibodies Against Human Pancreatic Ductal Adenocarcinoma Cells.

    Science.gov (United States)

    Higashi, Kiyoshi; Fujii, Nobuaki; Kushida, Masahiko; Yamada, Keita; Suzuki, Noriyuki; Saito, Koichi; Tachibana, Taro

    2016-06-01

    Pancreatic ductal adenocarcinoma is an aggressive tumor with a poor prognosis. Biomarkers that can detect the tumor in its early stages when it may be amenable to curative resection might improve prognosis. To discover novel markers expressed in primary pancreatic cancer, we generated a panel of monoclonal antibodies against pancreatic ductal adenocarcinoma cell line BxPC3 using a rat medial iliac lymph node method. The antigen recognized by 1B5A5 was expressed on the cell surface and secreted into the conditioned medium of BxPC3 cells, and characterized as glycoproteins with molecular mass between 60 and 90 kDa. A wide range of molecular weights of 1B5A5 antigen in several pancreatic cancer cell lines were observed. Immunohistochemistry using a human multiple organ tumor tissue array showed an enhanced expression of 1B5A5 antigen in pancreas, lung, stomach, breast, urinary bladder, colon, and cervix uteri cancers. Immunoprecipitation followed by proteomic analyses identified CEACAM6 as a 1B5A5 antigen. In addition, western blot analysis results indicated that the 1B5A5 epitope is located within an amino-terminal domain of CEACAM6. These results raised the possibility that our approach could lead to discovery of novel biomarkers for the early stage of cancers in a relatively short period of time.

  2. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia

    2011-01-01

    Objective: There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods: Side population(SP) cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting (FACS) was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results: Lung cancer cells could grow in a serum-free Medium(SFM) as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of

  3. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia

    2010-01-01

    Objective:There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs)has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods:Side population(SP)cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS)was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results:Lung cancer cells could grow in a serum-free Medium(SFM)as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion:SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of cancer stem

  4. Characterization of gastrins and their receptor in solid human gastric adenocarcinomas

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Eiland, Signe; Svendsen, Lars Bo;

    2013-01-01

    OBJECTIVE: The gastrin and the gastrin/CCK-B receptor genes are co-expressed in several carcinomas. The primary translational product, progastrin, however, is processed to several peptides of which only those that are α-amidated at their C-terminus are receptor ligands. So far, characterization...... of the progastrin-derived peptides in gastric cancer has not been reported. The authors therefore examined the molecular nature of gastrin and its receptor in human gastric carcinomas. MATERIALS AND METHODS: Twenty patients with adenocarcinoma underwent partial or total gastrectomy. In samples from each carcinoma...... blotting. RESULTS: α-Amidated gastrins were detectable in 16 of 20 carcinomas (median concentration 2.1 pmol/g tissue; range 0-386 pmol/g tissue). The tissue concentrations correlated closely to the gastrin mRNA contents (r = 0.75, p amidated processing intermediates...

  5. Bax is not involved in the resveratrol-induced apoptosis in human lung adenocarcinoma cells

    Science.gov (United States)

    Zhang, Wei-wei; Wang, Zhi-ping; Chen, Tong-sheng

    2010-02-01

    Resveratrol (RV) is a natural plant polyphenol widely present in foods such as grapes, wine, and peanuts. Previous studies indicate that RV has an ability to inhibit various stages of carcinogenesis and eliminate preneoplastic cells in vitro and in vivo. However, little is known about the molecular mechanism of RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cell. In this report, we analyzed whether Bax translocation from cytoplasm to mitochondria during RV-induced apoptosis in single living cell using onfocal microscopey. Cells were transfected with GFP-Bax plasmid. Cell counting kit (CCK-8) assay was used to assess the inhibition of RV on the cells viability. Apoptotic activity of RV was detected by Hoechst 33258 and propidium iodide (PI) staining. Our results showed that RV induced a dose-dependent apoptosis in which Bax did not translocate to mitochondrias.

  6. High fluence laser irradiation induces reactive oxygen species generation in human lung adenocarcinoma cells

    Science.gov (United States)

    Wang, Fang; Xing, Da; Chen, Tong-Sheng

    2006-09-01

    Low-power laser irradiation (LPLI) has been used for therapies such as curing spinal cord injury, healing wound et al. Yet, the mechanism of LPLI remains unclear. Our previous study showed that low fluences laser irradiation induces human lung adenocarcinoma cells (ASTC-a-1) proliferation, but high fluences induced apoptosis and caspase-3 activation. In order to study the mechanism of apoptosis induced by high fluences LPLI further, we have measured the dynamics of generation of reactive oxygen species (ROS) using H IIDCFDA fluorescence probes during this process. ASTC-a-1 cells apoptosis was induced by He-Ne laser irradiation at high fluence of 120J/cm2. A confocal laser scanning microscope was used to perform fluorescence imaging. The results demonstrated that high fluence LPLI induced the increase of mitochondria ROS. Our studies contribute to clarify the biological mechanism of high fluence LPLI-induced cell apoptosis.

  7. [Expression of aquaporins and its significance in human pulmonary adenocarcinoma cell line SPC-A-1].

    Science.gov (United States)

    Chen, Jie; Bai, Chunxue; Zhang, Min; Ren, Zhenyi; Hu, Jie

    2004-06-20

    To investigate the expression of aquaporins in human pulmonary adenocarcinoma cell line SPC-A-1. The expressions of aquaporin 1, aquaporin 3, aquaporin 4, and aquaporin 5 in mRNA level and their locations were determined in cell line SPC-A-1 respectively by RT-PCR and immunohistochemistry. The immunohistochemical stain showed aquaporin 3 and aquaporin 5 located on the membrane of SPC-A-1 cell, but no positive stain of aquaporin 1 and aquaporin 4 was observed. Both aquaporin 3 and aquaporin 5 mRNA expressed in SPC-A-1 cell line, and the expression level of aquaporin 5 mRNA was significantly higher than that of aquaporin 3 mRNA ( P SPC-A-1 cell line. Aquaporin 3 and aquaporin 5 express in SPC-A-1 cell, and their roles in water transport of SPC-A-1 cell should be further investigated.

  8. Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation.

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    Gijs Teklenburg

    Full Text Available BACKGROUND: Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown. METHODOLOGY/PRINCIPAL FINDINGS: We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1beta, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo. CONCLUSIONS: Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits

  9. Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

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    Atkinson, Stuart P.; Quiñonero, Alicia; Martínez, Sebastián; Pellicer, Antonio; Simón, Carlos

    2012-01-01

    Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. PMID:22291969

  10. [Environmental and genetic risk factors for endometrial carcinoma].

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    Sénéchal, Claire; Cottereau, Edouard; de Pauw, Antoine; Elan, Camille; Dagousset, Isabelle; Fourchotte, Virginie; Gauthier-Villars, Marion; Lae, Marick; Stoppa-Lyonnet, Dominique; Buecher, Bruno

    2015-03-01

    In France, endometrial cancer is at the first rank of gynecological cancers for cancer incidence, before ovarian and cervical cancers. In fact, the number of incident cases has been estimated to 7275 for the year 2012; the number of death due to endometrial cancer to 2025. This cancer is hormone-dependent and endogenous (reproductive factors) or exogenous (oral combined contraceptives, hormone replacement therapy) causes of exposition to estrogens are the major environmental risk factors for both types of endometrial cancers: type I or well-differentiated endometrioid adenocarcinomas; and type II including all other histological types: papillary serous adenocarcinomas, clear cell adenocarcinomas and carcinosarcomas, also known as malignant mixed Mullerian tumor, MMMT. Obesity, diabetes mellitus and adjuvant treatment of breast cancer with tamoxifen are also associated with an increased risk of endometrial cancer. Genetic factors may also be implicated in the pathogenesis of endometrial cancer either as "minor genetic factors" (susceptibility factors), which remain largely unknown and are responsible for the increased observed risk in relatives of women affected with endometrial cancer; or as major genetic factors responsible for hereditary forms and namely for Lynch syndrome whose genetic transmission is of autosomic dominant type. The appropriate recognition of Lynch syndrome is of critical importance because affected patients and their relatives should benefit from specific care. The aims of this review is to describe major environmental and genetic risk factors for endometrial cancer with specific attention to most recent advances in this field and to describe recommendations for care of at-risk women.

  11. Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.

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    Rao, C V; Desai, D; Kaul, B; Amin, S; Reddy, B S

    1992-11-16

    Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems.

  12. Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia

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    Kadirogullari, Pinar; Atalay, Cemal Resat; Sari, Mustafa Erkan

    2015-01-01

    Introduction Endometrial hyperplasia has been associated with the presence of concomitant endometrial carcinoma. In this study, patients who were diagnosed with endometrial hyperplasia and had hysterectomy, determination of the incidence of endometrial cancer accompanying postoperatively and clinical parameters associated with cancer are aimed. Materials and Methods Endometrial biopsies were taken from patients for various reasons and among them 158 patients diagnosed with endometrial hyperplasia from pathologic examination results were retrospectively evaluated. All of the patient’s age, parity, weight, transvaginal ultrasound measured by endometrial thickness, concomitant systemic disease (diabetes, hypertension, hypothyroidism), tamoxifen use, hormone use and whether in reproductive age or menopause were all questioned. Patients who applied with endometrial cancer, their cervical stromal involvement, lymph node involvement, cytology positivity and omental metastases were examined. Patients were classified according to their stage and grade. Patients who had intraoperative frozen were re-evaluated. Results Fifteen cases with preoperative endometrial hyperplasia diagnosed with endometrial cancer postoperatively, 2 cases had complex hyperplasia without atypia and 13 cases had complex atypical hyperplasia. The rate of preoperative hyperplasia with postoperative endometrial cancer was found to be 10.8% where by 15 cases of patients diagnosed with endometrial cancer postoperatively 11 cases were in postmenopausal period. In patients diagnosed with endometrial cancer according to their histologic types 14 cases had endometrioid adenocarcinoma while one patient with preoperative complex hyperplasia without atypia was diagnosed with serous papillary carcinoma postoperatively. Evaluation of stages in patients diagnosed with cancer, 7 cases of patients had stage IA, 7 cases of patients had stage IB, and 7 cases cases of patients with serous papillary carcinoma were

  13. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

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    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  14. Endometrial Hyperplasia

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    ... If your menstrual periods are irregular, birth control pills (oral contraceptives) may be recommended. They contain estrogen along with progestin. Other forms of progestin also may be taken. If you are overweight, losing weight may help. The risk of endometrial cancer increases with the degree of ...

  15. A prospective study of dietary acrylamide intake and the risk of breast, endometrial, and ovarian cancers

    Science.gov (United States)

    Wilson, Kathryn M.; Mucci, Lorelei A.; Rosner, Bernard A.; Willett, Walter C.

    2010-01-01

    Background Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiological studies of acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk of breast, endometrial, and ovarian cancers in a prospective cohort study. Methods We assessed acrylamide intake among 88,672 women in the Nurses’ Health Study using food frequency questionnaires administered every four years. Between 1980 and 2006 we identified 6301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk. Results We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk of endometrial cancer among high acrylamide consumers (adjusted relative risk [RR] for highest versus lowest quintile=1.41, 95% CI: 1.01–1.97, p-value for trend=0.03). We observed a non-significant suggestion of increased risk for ovarian cancer overall (RR 1.25, CI: 0.88–1.77, p-trend=0.12), with a significantly increased risk for serous tumors (RR 1.58, CI: 0.99–2.52, p-trend=0.04). Associations did not differ by smoking status. Conclusions We observed no association between acrylamide and breast cancer. Risk of endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers. Impact This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy. PMID:20693310

  16. Evaluation of human first trimester decidual and telomerase-transformed endometrial stromal cells as model systems of in vitro decidualization

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    Saleh Leila

    2011-12-01

    Full Text Available Abstract Background Decidualization, the differentiation process of maternal uterine stromal cells into secretory decidual cells, is a prerequisite for successful implantation and progression of pregnancy. For in vitro differentiation mostly primary human endometrial stromal cells (HESC isolated from uterine samples after hysterectomy for benign gynaecological diseases are utilised. However, a continuous supply of endometrial tissue is often lacking. Hence, we analysed whether cultivated human decidual stromal cells (HDSC prepared from first trimester pregnancy terminations may represent an alternative model system for in vitro decidualization. Moreover, based on the expression of critical marker genes these cells were compared to a previously established endometrial stromal cell line during in vitro differentiation. Methods HDSC isolated from decidual tissue attached to first trimester placentae, and telomerase-transformed human endometrial stromal cells (THESC were characterised by immunofluorescence and differentiated in vitro using either cyclic adenosine monophosphate (cAMP and/or estrogen (E2/progesterone (P4. Proliferation was measured by analyzing cumulative cell numbers. Expression of mRNAs encoding progesterone receptor (PR, prolactin (PRL, insulin-like growth factor binding protein-1 (IGFBP1, and Dickkopf-1 (DKK1 was evaluated using quantitative PCR after 3, 6, 9 and 12 days of in vitro differentiation. PRL and IGFBP-1 protein expression was investigated by enzyme-linked immunosorbent assay (ELISA and Western blotting, respectively. Furthermore, forkhead box O1A (FOXO1A, a critical transcription factor in decidualization, was analysed by immunofluorescence and Western blotting at two different time points of differentiation. Results Treatment with cAMP provoked morphological changes and growth arrest of THESC and HDSC, the latter showing loss of cells after 6 days of treatment. E2P4 stimulation did neither affect cell morphology nor

  17. Differentiation of human endometrial stem cells into endothelial-like cells on gelatin/chitosan/bioglass nanofibrous scaffolds.

    Science.gov (United States)

    Shamosi, Atefeh; Mehrabani, Davood; Azami, Mahmoud; Ebrahimi-Barough, Somayeh; Siavashi, Vahid; Ghanbari, Hossein; Sharifi, Esmaeel; Roozafzoon, Reza; Ai, Jafar

    2017-02-01

    The capacity of gelatin/chitosan/bioactive glass nanopowders (GEL/CS/BGNPs) scaffolds was investigated for increasing human endometrial stem cells (hEnSCs) differentiation into the endothelial cells in the presence of angiogenic factors. GEL/CS nanofibrous scaffold with different contents of BGNPs were fabricated and assessed. Expression of endothelial markers (CD31, vascular endothelial cadherin (VE-cadherin), and KDR) in differentiated cells was evaluated. Results showed the diameter of nanofiber increases with decreasing the BG content in GEL/CS scaffolds. Moreover, in vitro study indicated that the GEL/CS/BGNPs scaffold with 1.5% BGNPs content provided a suitable three-dimensional structure for endothelial cells differentiation. Thus, the GEL/CS/BGNPs scaffold can be recommended for blood vessels repair.

  18. Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

    Science.gov (United States)

    2017-08-23

    Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

  19. Regulation of human endometrial stromal proliferation and differentiation by C/EBPβ involves cyclin E-cdk2 and STAT3.

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    Wang, Wei; Taylor, Robert N; Bagchi, Indrani C; Bagchi, Milan K

    2012-12-01

    During each menstrual cycle, the human uterus undergoes a unique transformation, known as decidualization, which involves endometrial stromal proliferation and differentiation. During this process, the stromal cells are transformed into decidual cells, which produce factors that prepare the uterus for potential embryo implantation. We previously identified the transcription factor CCAAT/enhancer-binding protein (C/EBP)β as a regulator of endometrial stromal proliferation and differentiation in mice. In this study, we addressed the role of C/EBPβ in human endometrial decidualization. Using small interfering RNA targeted to C/EBPβ mRNA, we demonstrated that C/EBPβ controls the proliferation of primary human endometrial stromal cells (HESCs) by regulating the expression of several key cell cycle-regulatory factors during the G(1)-S phase transition. Additionally, loss of C/EBPβ expression blocked the differentiation of HESCs in response to estrogen, progesterone, and cyclic AMP. Gene expression profiling of normal and C/EBPβ-deficient HESCs revealed that the receptor for the cytokine IL-11 and its downstream signal transducer signal transducer and activator of transcription 3 (STAT3) are targets of regulation by C/EBPβ. Chromatin immunoprecipitation analysis indicated that C/EBPβ controls the expression of STAT3 gene by directly interacting with a distinct regulatory sequence in its 5'-flanking region. Attenuation of STAT3 mRNA expression in HESCs resulted in markedly reduced differentiation of these cells, indicating an important role for STAT3 in decidualization. Gene expression profiling, using STAT3-deficient HESCs, showed an extensive overlap of pathways downstream of STAT3 and C/EBPβ during stromal cell differentiation. Collectively, these findings revealed a novel functional link between C/EBPβ and STAT3 that is a critical regulator of endometrial differentiation in women.

  20. 1α,25(OH) 2D3 Sensitive Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Ishikawa Cells.

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    Zeng, Ni; Zhou, Yuetao; Zhang, Shaqiu; Singh, Yogesh; Shi, Bing; Salker, Madhuri S; Lang, Florian

    2017-01-01

    Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions and lactate, which is in part accomplished by Na+/H+ exchangers, such as NHE1 and monocarboxylate transporters, such as MCT4. An effect of 1,25(OH)2D3 on those transport processes has, however, never been reported. As cytosolic pH impacts on apoptosis, the study further explored the effect of 1,25(OH)2D3 on apoptosis and on the apoptosis regulating kinase AKT, transcription factor Forkhead box O-3 (FOXO3A) and B-cell lymphoma protein BCL-2. In human endometrial adenocarcinoma (Ishikawa) cells, cytosolic pH (pHi) was determined utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, NHE1 and MCT4 transcript levels using qRT-PCR, NHE1, MCT4, total & phospho AKT, total & phospho-FOXO3A and BCL-2 protein abundance by Western blotting, lactate concentration in the supernatant utilizing a colorimetric enzyme assay and cell death quantification using CytoTox 96®, Annexin V and Propidium Iodide staining. A 24 hours treatment with 1,25(OH)2D3 (100 nM) significantly increased cytosolic pH (pHi), significantly decreased Na+/H+ exchanger activity, NHE1 and MCT4 transcript levels as well as protein abundance and significantly increased lactate concentration in the supernatant. Treatment of Ishikawa cells with 1,25(OH)2D3 (100 nM) further triggered apoptosis, an effect paralleled by decreased phosphorylation of AKT and FOXO3A as well as decreased abundance of BCL-2. In Ishikawa cells 1,25(OH)2D3 is a powerful stimulator of glycolysis, an effect presumably due to

  1. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma.

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    Charlotta Hedner

    Full Text Available Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR and 3 (HER3, as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma.Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology.High EGFR expression was an independent risk factor for shorter overall survival (OS, whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods.

  2. Neurotensin is a Versatile Modulator of In Vitro Human Pancreatic Ductal Adenocarcinoma Cell (PDAC Migration

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    Tatjana Mijatovic

    2007-01-01

    Full Text Available Background: While the neurotensin (NT roles in pancreatic cancer growth are well documented, its effects on pancreatic cancer cell migration have not been described. Methods: The NT-induced effects on the migration process of human pancreatic ductal adenocarcinoma cells (PDACs were characterized by means of various assays including computer-assisted video-microscopy, fluorescence microscopy, ELISA-based, small GTPase pull-down and phosphorylation assays. Results: The NT-induced modifications on in vitro PDACs migration largely depended on the extra-cellular matrix environment and cell propensity to migrate collectively or individually. While NT significantly reduced the level of migration of collectively migrating PDACs on vitronectin, it significantly increased the level of individually migrating PDACs. These effects were mainly mediated through the sortilin/NTR3 receptor. Neurotensin both induced altered expression of αV and β5 integrin subunits in PDACs cultured on vitronectin resulting in modified adhesion abilities, and caused modifications to the organization of the actin cytoskeleton through the NT-mediated activation of small Rho GTPases. While the NT effects on individually migrating PDACs were mediated at least through the EGFR/ERK signaling pathways, those on collectively migrating PDACs appeared highly dependent on the PI 3-kinase pathway. Conclusion: This study strongly suggests the involvement of neurotensin in the modulation of human PDAC migration.

  3. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells.

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    de Vasconcelos, Alana; Campos, Vinicius Farias; Nedel, Fernanda; Seixas, Fabiana Kömmling; Dellagostin, Odir A; Smith, Kevin R; de Pereira, Cláudio Martin Pereira; Stefanello, Francieli Moro; Collares, Tiago; Barschak, Alethéa Gatto

    2013-06-01

    Recent studies report that chalcones exhibit cytotoxicity to human cancer cell lines. Typically, the form of cell death induced by these compounds is apoptosis. In the context of the discovery of new anticancer agents and in light of the antitumour potential of several chalcone derivatives, in the present study, we synthesized and tested the cytotoxicity of six chalcone derivatives on human colon adenocarcinoma cells. Six derivatives of 3-phenyl-1-(thiophen-2-yl) prop-2-en-1-one were prepared and characterized on the basis of their (1) H and (13) C NMR spectra. HT-29 cells were treated with synthesized chalcones on two concentrations by three different incubation times. Cells were evaluated by cell morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry (annexin V) and gene expression analyses to determine the cytotoxic way. Chalcones 3-(4-bromophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C06) and 3-(2-nitrophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C09) demonstrated higher cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay. These data were confirmed by a decreased expression of anti-apoptotic genes and increased pro-apoptotic genes. Our findings indicate in summary that the cytotoxic activity of chalcone C06 on colorectal carcinoma cells occurs by apoptosis.

  4. Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells.

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    Yu, Yang; Yu, Xiaofeng; Ma, Jianxia; Tong, Yili; Yao, Jianfeng

    2016-07-01

    The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway plays a significant role in colorectal adenocarcinoma. NVP-BEZ235 (dactolisib) is a novel dual inhibitor of PI3K/mTOR. The effects of NVP-BEZ235 in human colorectal adenocarcinoma are still unclear. In the present study, we aimed to explore the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells. HT-29 human colorectal adenocarcinoma cells were treated with NVP-BEZ235 (0, 0.001, 0.01, 0.1, 1 and 3 µM) for 24 and 48 h, respectively. Cells were also treated with NVP-BEZ235 (0.1 µM), DDP (100, 300 and 1,000 µM), and NVP-BEZ235 (0.1 µM) combined with DDP (100, 300 and 1,000 µM) respectively, and cultured for 24 h after treatment. MTT assay was utilized to evaluate the effects of NVP-BEZ235 alone or NVP-BEZ235 combined with cis-diamminedichloroplatinum (DDP) on proliferation of HT-29 cells. Cell wound-scratch assay was used detect cell migration. In addition, expression of microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B and LC3B) in HT-29 cells was detected by immunofluorescence at 48 h after NVP-BEZ235 (1 µM) treatment. Expression of proteins involved in cell cycle and proliferation (p-Akt, p-mTOR and cyclin D1), apoptosis (cleaved caspase-3), and autophagy (cleaved LC3B and Beclin-1) were detected by western blot analysis. NVP-BEZ235 inhibited the proliferation and migration of HT-29 human colorectal adenocarcinoma cells. NVP-BEZ235 decreased protein expression of p-Akt, p-mTOR and cyclin D1, and increased protein expression of cleaved caspase-3, cleaved LC3B and Beclin-1 as the concentrations and the incubation time of NVP-BEZ235 increased. In addition, NVP-BEZ235 and DDP had synergic effects in inhibiting cell proliferation and migration. The expression of protein involved in apoptosis (cleaved caspase-3) was higher in drug combination group compared to the NVP-BEZ235 single treatment group. NVP-BEZ235

  5. Endometrial Cancer Prevention

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    ... risk of endometrial cancer: Endometrial hyperplasia Estrogen Tamoxifen Obesity, weight gain, metabolic syndrome, and diabetes Genetic factors The following protective factors decrease the risk of ...

  6. Characterization of EN-1078D, a poorly differentiated human endometrial carcinoma cell line: a novel tool to study endometrial invasion in vitro

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    Asselin Eric

    2007-09-01

    Full Text Available Abstract Background To date, tools to study metastasis in endometrial cancers are insufficiently developed. The aim of this study was to characterize the cell line EN-1078D, a new endometrial carcinoma cell line derived from a metastasis to the ovary. Methods and Results Cells were characterized using cytology, transmission electron microscopy, karyotyping and morphological appearance in culture. Molecular features were determined by RT-PCR, Western Blot, FISH and sequencing. MTT proliferation assays were performed to investigate the sensitivity of EN-1078D to anticancer agents such as cisplatin and doxorubicin. Also, subcutaneous and intravenous injections in nude mice were done to test the tumorigenic and metastatic properties of EN-1078D cells. Our results indicate that EN-1078D cells express both oestrogen receptors isoforms (ER alpha and ER beta and also low levels of progesterone receptor B (PR-B. In addition, this cell line expresses high levels of MMP-2 and MMP-14 mRNA, low levels of TIMP-1 and TIMP-2 transcripts and no detectable levels of MMP-9 mRNA. Moreover, all nude mice developed tumors by subcutaneous injections and cell invasion was observed in vitro in response to TGF-beta 3. Her-2/neu was not overamplified but mutations in the C-2 domain of PTEN gene as well as codon 12 of the K-Ras gene were found. Finally, EN-1078D shows sensitivity to drugs commonly used in chemotherapy such as cisplatin and doxorubicin: IC50 of 2.8 μM of cisplatin after 72 hours of exposure and 0.54 μM of doxorubicin after 48 hours. Conclusion Taken together, these results suggest that EN-1078D will be an excellent tool to study the properties of metastatic endometrial cancer cells in vitro and their regulation by sex steroids.

  7. Pesquisa da prevalência do papilomavírus humano em amostras de tecido endometrial normal e com carcinoma pela técnica de PCR Search for human papillomavirus in samples of normal endometrial tissue and tissue with carcinoma by the PCR technique

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    Edison Natal Fedrizzi

    2004-05-01

    Full Text Available OBJETIVO: comparar a prevalência da presença do DNA do papilomavírus humano (HPV pela técnica de PCR em amostras de tecido endometrial normal e com carcinoma endometrial de mulheres submetidas a tratamento cirúrgico (histerectomia ou carcinoma endometrial e doença benigna. MÉTODOS: trata-se de um estudo observacional do tipo caso-controle onde foram avaliadas 100 mulheres (50 com endométrio normal e 50 com carcinoma endometrial quanto a presença do DNA do HPV em amostra tecidual conservada em blocos de parafina, pelo método de PCR. Foram excluídos os casos de carcinoma endometrial cujo sítio primário da lesão era duvidoso ou com história prévia ou atual de lesões pré-neoplásicas ou carcinoma do trato genital inferior. Variáveis como idade, tabagismo, trofismo endometrial, diferenciação escamosa e grau de diferenciação tumoral foram também avaliadas. RESULTADOS: o risco relativo estimado da presença do HPV foi o mesmo nas mulheres com e sem carcinoma endometrial. O HPV foi detectado em 8% dos casos de carcinoma e 10% no endométrio normal. Apesar de o HPV ter sido detectado 3,5 vezes mais em mulheres fumantes no grupo sem carcinoma, não houve diferença estatística. A presença do HPV também não esteve correlacionada com a idade das mulheres, trofismo endometrial, diferenciação escamosa e grau de diferenciação tumoral. Os HPV 16 e 18 (5 dos casos com o tipo 16 e 4 com o tipo 18 foram os vírus mais freqüentemente encontrados, tanto no tecido endometrial normal, quanto no carcinomatoso. Nenhum vírus de baixo risco oncogênico foi detectado nas amostras. CONCLUSÃO: o HPV está presente no tecido endometrial de mulheres com carcinoma endometrial na mesma proporção que nas com tecido endometrial normal, não se demonstrando a possível associação deste vírus no desenvolvimento do carcinoma endometrial.OBJECTIVE: to compare the prevalence of DNA of human papillomavirus (HPV, in samples of normal endometrial

  8. New model of in-situ xenograft lymphangiogenesis by a human colonic adenocarcinoma cell line in nude mice.

    Science.gov (United States)

    Sun, Jian-Jun; Jing, Wei; Ni, Yan-Yan; Yuan, Xiao-Jian; Zhou, Hai-Hua; Fan, Yue-Zu

    2012-01-01

    To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenografts in-situ than in the negative control group (both Pconformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

  9. Endometrial polyp surveillance in premenopausal breast cancer patients using tamoxifen

    Science.gov (United States)

    Jeon, Se Jeong; Lee, Jae Il; Kim, Hee Seung; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang

    2017-01-01

    Objective To describe the endometrial pathologic lesions in premenopausal breast cancer patients with a history of tamoxifen (TMX) use. Methods We retrospectively reviewed the medical records of 120 premenopausal breast cancer patients with a history of TMX use that had undergone a gynecological examination. Results Among 120 patients, 44.2% (n=53) were asymptomatic with an endometrial thickness ≥5 mm, as assessed by transvaginal ultrasonography. Of the patients that reported abnormal uterine bleeding, 5% (n=6) had an endometrial thickness <5 mm and 20% (n=24) had an endometrial thickness ≥5 mm by transvaginal ultrasonography. The final group of patients were asymptomatic, but showed an abnormal endometrial lesion, such as an endometrial polyp, by transvaginal ultrasonography (30.8%, n=37). Of the 56 benign lesions that were histologically reviewed, 50 (41.7%) were endometrial polyps, 3 (2.5%) were submucosal myomas, 2 (1.7%) were endometrial hyperplasias, and 1 (0.8%) was chronic endometritis. There were 64 (53.3%) other non-pathologic conditions, including secreting, proliferative, and atrophic endometrium, or in some cases, there was insufficient material for diagnosis. In our data, only one case was reported as a complex hyperplasia without atypia arising from an endometrial polyp, and one patient was diagnosed with endometrioid adenocarcinoma. Conclusion For premenopausal breast cancer patients with a history of TMX use, the majority of the patients were asymptomatic, and endometrial polyps were the most common endometrial pathology observed. Therefore, we believe that endometrial assessment before starting TMX treatment, and regular endometrial screening throughout TMX treatment, are reasonable suggestions for premenopausal breast cancer patients. PMID:28217668

  10. Selected flavonoids potentiate the toxicity of cisplatin in human lung adenocarcinoma cells: A role for glutathione depletion

    OpenAIRE

    Kachadourian, Remy; LEITNER, VHEATHER M.; Day, Brian J.

    2007-01-01

    Adjuvant therapies that enhance the anti-tumor effects of cisplatin are actively being pursued. Growing evidence supports the involvement of mitochondrial dysfunction in the anti-cancer effect of cis-diammineplatinum(II) dichloride (cisplatin, CDDP). We examined the potential of using selective flavonoids that are effective in depleting tumor cells of glu-tathione (GSH) to potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549) cells. We found that cisplatin (40 μM, 48-...

  11. Effects of the Spider Venom on proliferation of Human Lung Adenocarcinoma Cell A549

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    Zengxiang HU

    2010-10-01

    Full Text Available Background and objective The spider venom may inspire new drugs to treat cancer. The aim of this study is to investigate the effects and mechanisms of spider venom on lung adenocarcinoma cell A549. Methods The proliferation of lung adenocarcinoma A549 cells was detected by MTT. The apoptosis rate was observed with MTT assay and flow cytometer. The activity of catalase was detected by colorimetry. The malondialdehyde (MDA content was determined by improved thiobarbituric acid fluorometric method. The expression of P38MAPK protein was analyzed with Western blot. Results Spider venom can remarkably inhibite the proliferation of lung adenocarcinoma A549 cells, increased activity of catalase and MDA content, down-regulated expression of P38MAPK compared with the control group. Conclusion The reduced proliferation of lung adenocarcinoma A549 cells by spider venom is may be associated with the increased of activity of catalase and MDA content and decreased expression of P38MAPK.

  12. Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines.

    Science.gov (United States)

    Mahmoud, Mona F; El Shazly, Shimaa M

    2013-01-01

    Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.

  13. Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

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    Pan Shiow-Lin

    2009-05-01

    Full Text Available Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1 in denbinobin-induced apoptosis in human lung adenocarcinoma (A549 cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN, two antioxidants (N-acetyl-L-cysteine (NAC and glutathione (GSH, a c-Jun N-terminal kinase (JNK inhibitor (SP600125, and an activator protein-1 (AP-1 inhibitor (curcumin. Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

  14. Role of Autophagy in the Radiosensitivity of Human Lung Adenocarcinoma A549 Cells

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    Liyao XU

    2016-12-01

    Full Text Available Background and objective Radiotherapy is an important treatment for lung cancer. The poor prognosis of lung cancer is largely caused by the high recurrence rate and metastasis of the tumor. Autophagy, which can be induced by radiotherapy, might be associated with DNA repair. The aim of this study is to investigate whether activating autophagy using rapamycin can enhance the radiosensitivity of lung cancer cells and clarify the association of autophagy with DNA repair. Methods The human adenocarcinoma A549 cell line was selected as the experimental subject. The specimens were divided into three groups: control (N, radiation (R, and Rapamycin and radiation (R+RAPA. The protein levels of γ-H2AX, Rad51, Ku70/Ku80, p62, and LC3 were determined by Western blot. Autophagosome was observed under a transmission electron microscope, and SF was determined by colony formation assay. Results Compared with group R, the activity of autophagy and the protein expression levels of Rad51 and Ku70/80 were remarkably increased in group R+RAPA. Conclusion The radiosensitivity of lung cancer can be promoted by activating autophagy via treatment with Rapamycin, and the process may be associated with DNA repair.

  15. RESTRICTION ENDONUCLEASE ANALYSIS OF MITOCHONDRIAL DNA FROM HUMAN LUNG ADENOCARCINOMA CELL LINE SPC-A-1

    Institute of Scientific and Technical Information of China (English)

    HU Yide; QIAN Guisheng; CHEN Weizhong; LI Shuping; WANG Guansong; MAO Baoling

    1999-01-01

    Objective: To understand the role of mitochondrial DNA (mtDNA) in carcinogenesis. Methods: single-step method was used to isolate the mtDNA from human lung adenocarcinoma cell line SPC-A-1. The mtDNA was analyzed by restriction fragment length polymorphism (RFLP) with 11 kinds of restriction endonuclease, which were Pvu Ⅱ, Xho Ⅰ, Pst Ⅰ, EcoR Ⅰ,BstE Ⅱ, Hind Ⅲ, Hpa Ⅰ, Bcl Ⅰ, EcoR Ⅴ, Sca Ⅰ and Xba Ⅰ.Restriction map of mtDNA from SPC-A-1 cell was obtained by the single and double-digestion method.Results: It was found that no variation at 32 restrictionsites could be detected in the coding region of mtDNA from SPC-A-1 cell line. But a new site was found at nucleotide 16276 (EcoR Ⅴ) within the noncoding region.Conclusion: These results indicate that the primary structure of gene coding region of mtDNA isolated from SPC-A-1 cell is highly stable. While the major variation of nucleotide is probably located in the noncoding region.

  16. Effects of Spinach Powder Fat-Soluble Extract on Proliferation of Human Gastric Adenocarcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    HE TAo; HUANG CHENG-YU; CHEN HAl; HOU YUN-HUA

    1999-01-01

    Four kinds of assays were used to study the effect of a fat-soluble extract of spinach powder(SPFE) on the proliferation of human gastric adenocarcinoma cell line (SGC-7901) in vitro.These studies included: ( i ) cell growth assay, ( ii ) colony forming assay, ( iii ) MTT colorimetric assay, and ( iv ) 3H-TdR incorporation assay. The concentrations of SPFE expressed as the level of β-carotene in the medium were 2 × 10-s, 2 × 10-7 and 2 × 10-6 mol/L β-carotene in assays ( i ) ~ ( iii ), but 4 × 10-8, 4 × 10-7 and 4 × 10-6 mol/L β-carotene in assay ( iV ) respectively. The results indicated that SPFE inhibited the proliferation and colony forming ability of SGC-7901 cells. And in MTT assay, SPFE inhibited the viability of SGC-7901 cells, but no inhibitory effect of SPFE was observed on the viability of lymphocytes in peripheral blood of healthy people. Finally, in the 3H-TdR incorporation test, both SPFE and β-carotene showed significant inhibitory effects on DNA synthesis in SGC-7901 cells, but SPFE was more effective than 3-carotene.

  17. Evaluation of lignan (-)-cubebin extracted from Piper cubeba on human colon adenocarcinoma cells (HT29).

    Science.gov (United States)

    Niwa, Andressa Megumi; de Paula, Natalia Aparecida; Vesenick, Diogo Campos; Sartori, Daniele; Maistro, Edson Luis; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2016-01-01

    The dibenzylbutyrolactone lignan (-)-cubebin, which is extracted from the seeds of the pepper Piper cubeba, has shown promise as an anti-inflammatory, analgesic, leishmanicidal, antiproliferative, and trypanocidal compound. Given the therapeutic potential of (-)-cubebin, this study aimed to investigate its safety profile by analyzing cytotoxicity, mutagenicity, cell proliferation kinetics, induction of apoptosis, and expression of pro-apoptotic genes in human colon adenocarcinoma cells (HT29) exposed to (-)-cubebin. MTT cytotoxicity assays demonstrated that (-)-cubebin was cytotoxic only at 280 µM, whereas it was not cytotoxic at 2.8, 14, or 28 µM. Data demonstrated that (-)-cubebin was not mutagenic as evidenced by a micronucleus (MN) assay, did not alter cell-growth kinetics over 4 d, and showed absence of induced apoptosis after 24 h. Further, CASP8 and CASP9 gene expression was not markedly changed in HT29 cells exposed to 28 µM or 70 µM (-)-cubebin for 12 h. Based on our observations, (-)-cubebin was cytotoxic at a concentration of 280 µM, suggesting that the use of this concentration should be avoided. However, lower concentrations exerted no apparent damaging effects, indicating that this lignan is safe to use for pharmacological purposes at certain concentrations.

  18. Capsaicin-induced cell death in a human gastric adenocarcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    Yi-Ching Lo; Yuan-Chen Yang; I-Chieh Wu; Fu-Chen Kuo; Chi-Ming Liu; Hao-Wei Wang; Chao-Hung Kuo; Jeng-Yi Wu; Deng-Chyang Wu

    2005-01-01

    AIM: Capsaicin, a pungent ingredient found in red pepper,has long been used in spices, food additives, and drugs.Cell death induced by the binding of capsaicin was examined in a human gastric adenocarcinoma cell line (AGS cells).METHODS: By using XTT-based cytotoxicityassay, flow cytometry using the TUNEL method, and quantitation of DNA fragmentation, both cell death and DNA fragmentation were detected in AGS cells treated with capsaicin. By using Western blotting methods, capsaicin reduced the expression of Bcl-2, the antiapoptotic protein, in AGS cells in a concentration-dependent manner.RESULTS: After incubation of AGS cells with capsaicin for 24 h, cell viability decreased significantly in a dose-dependent manner. After incubation of AGS cells with capsaicin for 24 h, apoptotic bodies also significantly increased, and were again correlated with the dose of capsaicin. When the concentration of capsaicin was 1 mmol/L, the amount of DNA fragments also increased. Similar results werealso in the lower traces.CONCLUSION: These results suggest that capsaicininduced cell death might be via a Bcl-2 sensitive apoptotic pathway. Therefore, capsaicin might induce protection from gastric cancer.

  19. Proapoptotic effects of new pentabromobenzylisothiouronium salts in a human prostate adenocarcinoma cell line.

    Science.gov (United States)

    Koronkiewicz, Mirosława; Kazimierczuk, Zygmunt; Szarpak, Kinga; Chilmonczyk, Zdzisław

    2012-01-01

    Prostate cancer is the second most common cancer in elderly men worldwide and its incidence rate is rising continuously. Agents capable of inducing apoptosis in prostate cancer cells seem a promising approach to treat this malignancy. In this study we describe the synthesis of a number of novel N- and N,N'-substituted S-2,3,4,5,6-pentabromobenzylisothiouronium bromides and their activity against the human prostate adenocarcinoma PC3 cell line. All the compounds produced changes in mitochondrial transmembrane potential and cell cycle progression, showed a cytostatic effect and induced apoptosis in the tested cancer line in a concentration- and time-dependent manner. The most effective compounds ZKK-3, ZKK-9 and ZKK-13 produced, at 20 microM concentration, apoptosis in 42, 46, and 66% of the cells, respectively, after 48 h incubation. Two selected S-2,3,4,5,6-pentabromobenzylisothiouronium bromides (ZKK-3, ZKK-9) showed also a synergic proapoptotic effect with the new casein kinase II inhibitor 2-(4-methylpiperazin-1-yl)-4,5,6,7-tetrabromo-1H-benzimidazole (TBIPIP) in the PC3 cell line.

  20. Previous heat shock treatment inhibits Mayaro virus replication in human lung adenocarcinoma (A549) cells.

    Science.gov (United States)

    Virgilio, P L; Godinho-Netto, M C; Carvalho Mda, G

    1997-01-01

    Human lung adenocarcinoma cells (A549) were submitted to mild or severe heat shock (42 degrees C or 44 degrees C) for 1 h, while another group of cells was double-heat-shocked (submitted to 42 degrees C for 1 h, returned to 37 degrees C for 3 h, then exposed to 44 degrees C for 1 h). After each heat treatment, the cells were infected with Mayaro virus for 24 h and incubated at 37 degrees C. The results showed that the double-heat-shocked thermotolerant cells exhibited a 10(4)-fold virus titre inhibition, despite the recovery of protein synthesis and original morphology 24 h post-infection. In contrast, cells submitted to mild or severe heat shock exhibited weaker inhibition of Mayaro virus titre (10(2)-fold). The mildly heat-shocked cells also presented a full recovery in protein synthesis, which was not observed in severely heat-shocked cells. These results indicate that exposure of A549 cells to a mild or to a double heat shock treatment before Mayaro virus infection induces an antiviral state.

  1. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

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    Yang Yang

    Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

  2. Photodynamic activity of a glucoconjugated silicon(IV) phthalocyanine on human colon adenocarcinoma.

    Science.gov (United States)

    Chan, Crystal M H; Lo, Pui-Chi; Yeung, Sin-Lui; Ng, Dennis K P; Fong, Wing-Ping

    2010-07-15

    Photodynamic therapy (PDT) involves the use of a non-toxic photosensitizer which exhibits a killing effect upon activation by light. In the past few years, we have synthesized a number of novel second generation photosensitizers with superior properties, most of them are phthalocyanines. Among them, the glucoconjugated silicon(IV) phthalocyanine (SiPcGlu) shows potent phototoxicity against human colorectal adenocarcinoma HT29 cells. In the present study, its action mechanism was investigated. The initiation of apoptosis by SiPcGlu-PDT, subsequent to reactive oxygen species production, was shown by the results of TUNEL assay, annexin V and propidium iodide staining and DNA ladder pattern analysis. Confocal microscopy revealed the presence of SiPcGlu in lysosome, mitochondria and endoplasmic reticulum. SiPcGlu-PDT did not cause any damage to the lysosomal membrane; whereas in the mitochondria, it caused membrane depolarization and the release of cytochrome c into the cytosol, which subsequently brought about caspase-3 activation. In the endoplasmic reticulum, the treatment led to Ca(2+) release and an increase in the expression level of the chaperone protein GRP78. These observations suggest that SiPcGlu-PDT triggered the apoptotic pathways in both mitochondria and endoplasmic reticulum, but not the lysosome. A preliminary study of the photodynamic activity of SiPcGlu in the in vivo animal model was also carried out. It retarded tumor growth in HT29 tumor-bearing nude mice while causing no apparent toxicity to the animal.

  3. Inositol Hexakisphosphate Mediates Apoptosis in Human Breast Adenocarcinoma MCF-7 Cell Line via Intrinsic Pathway

    Science.gov (United States)

    Agarwal, Rakhee; Ali, Nawab

    2010-04-01

    Inositol polyphosphates (InsPs) are naturally occurring compounds ubiquitously present in plants and animals. Inositol hexakisphosphate (InsP6) is the most abundant among all InsPs and constitutes the major portion of dietary fiber in most cereals, legumes and nuts. Certain derivatives of InsPs also regulate cellular signaling mechanisms. InsPs have also been shown to reduce tumor formation and induce apoptosis in cancerous cells. Therefore, in this study, the effects of InsPs on apoptosis were studied in an attempt to investigate their potential anti-cancer therapeutic application and understand their mechanism of action. Acridine orange and ethidium bromide staining suggested that InsP6 dose dependently induced apoptosis in human breast adenocarcinoma MCF-7 cells. Among InsPs tested (InsP3, InsP4, InsP5, and InsP6), InsP6 was found to be the most effective in inducing apoptosis. Furthermore, effects of InsP6 were found most potent inducing apoptosis. Etoposide, the drug known to induce apoptosis in both in vivo and in vitro, was used as a positive control. Western blotting experiments using specific antibodies against known apoptotic markers suggested that InsP6 induced apoptotic changes were mediated via an intrinsic apoptotic pathway.

  4. [Effect of endothelin-1 on the proliferation of human lung adenocarcinoma cell SPC-A1].

    Science.gov (United States)

    Ye, Qianjun; Zhou, Juan; Zhang, Weimin

    2007-02-20

    Endothelin-1 (ET-1) is a potent mitogen involved in tumor cell growth and angiogenesis. The aim of this study is to explore the effect of ET-1 on the proliferation of human lung adenocarcinoma cells SPC-A1. Cell number was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide] assay. Cell cycle was detected by flow cytometry. ET-1 (1×10⁻¹⁵ -1×10⁻⁸ mol/L) enhanced SPC-A1 cell growth in a dose-dependent manner in vitro, with the greatest effect beginning at 1×10⁻¹¹ mol/L. Effect of ET-1 (1×10⁻¹⁰ mol/L) on the proliferation of SPC-A1 cells was completely blocked by BQ123 (1×10⁻⁷ mol/L), a highly selective endothelin receptor A (ETA) antagonist (P SPC-A1 cells (P SPC-A1 cell cycle. ET-1 enhances SPC-A1 cell proliferation by the activation of ETA receptor. Ca(2+) influx from voltage dependent calcium-channel contributes to this process.

  5. Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection

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    Wang Yan

    2007-10-01

    Full Text Available Abstract Background The incidence of gastric cardiac adenocarcinoma (GCA has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised. Methods In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM from paired surgical specimens of human GCA. Results Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses. Conclusion These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.

  6. Boletus edulis biologically active biopolymers induce cell cycle arrest in human colon adenocarcinoma cells.

    Science.gov (United States)

    Lemieszek, Marta Kinga; Cardoso, Claudia; Ferreira Milheiro Nunes, Fernando Hermínio; Ramos Novo Amorim de Barros, Ana Isabel; Marques, Guilhermina; Pożarowski, Piotr; Rzeski, Wojciech

    2013-04-25

    The use of biologically active compounds isolated from edible mushrooms against cancer raises global interest. Anticancer properties are mainly attributed to biopolymers including mainly polysaccharides, polysaccharopeptides, polysaccharide proteins, glycoproteins and proteins. In spite of the fact that Boletus edulis is one of the widely occurring and most consumed edible mushrooms, antitumor biopolymers isolated from it have not been exactly defined and studied so far. The present study is an attempt to extend this knowledge on molecular mechanisms of their anticancer action. The mushroom biopolymers (polysaccharides and glycoproteins) were extracted with hot water and purified by anion-exchange chromatography. The antiproliferative activity in human colon adenocarcinoma cells (LS180) was screened by means of MTT and BrdU assays. At the same time fractions' cytotoxicity was examined on the human colon epithelial cells (CCD 841 CoTr) by means of the LDH assay. Flow cytometry and Western blotting were applied to cell cycle analysis and protein expression involved in anticancer activity of the selected biopolymer fraction. In vitro studies have shown that fractions isolated from Boletus edulis were not toxic against normal colon epithelial cells and in the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells. The best results were obtained in the case of the fraction designated as BE3. The tested compound inhibited cancer cell proliferation which was accompanied by cell cycle arrest in the G0/G1-phase. Growth inhibition was associated with modulation of the p16/cyclin D1/CDK4-6/pRb pathway, an aberration of which is a critical step in the development of many human cancers including colon cancer. Our results indicate that a biopolymer BE3 from Boletus edulis possesses anticancer potential and may provide a new therapeutic/preventive option in colon cancer chemoprevention.

  7. Isolated humeral recurrence in endometrial carcinoma

    Science.gov (United States)

    Devdas, Santosh Kumar; Digumarti, Leela; Digumarti, Raghunadharao; Patro, Kunha Charan; Nutakki, Ramakoteswararao

    2016-01-01

    Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare. We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1 endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis, 2 years after surgery and adjuvant radiotherapy for primary disease. Imaging, bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated metastatic adenocarcinoma. She was treated with local radiotherapy followed by six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid, monthly. She is symptom-free after the treatment and at a first follow-up visit after 3 months. PMID:27688615

  8. A new case of primary signet-ring cell carcinoma of the cervix with prominent endometrial and myometrial involvement: Immunohistochemical and molecular studies and review of the literature

    Directory of Open Access Journals (Sweden)

    Giordano Giovanna

    2012-01-01

    Full Text Available Abstract Background As a rule, endocervical tumours with signet-ring cell are classed as metastatic extra-genital neoplasms. In a patient aged 45 years, we describe primary cervical signet-ring cell carcinoma (PCSRCC characterized by prominent endometrial and myometrial involvement, simulating primary endometrial adenocarcinoma with cervical extension. In addition, a review was made of the literature to identify the clinical and pathological features of this rare malignancy. Case presentation A 45-year-old woman was referred to our Gynaecology Department due to persistent abnormal vaginal bleeding. Transvaginal ultrasonography showed slight endometrial irregularities in the whole uterine cavity suggestive of endometrial neoplasms. Pelvic magnetic resonance imaging revealed diffuse enlargement of the cervix, which had been replaced by a mass. Induration extended to the parametria and sigmoid colon fat. Histological examination of endometrial curettage and a cervical biopsy revealed a neoplasm characterized by neoplastic signet-ring cells and trabecular structures. Immunohistochemical analysis and molecular studies showed certain findings consistent with a cervical neoplasm, such as positivity to CEA, keratin 7, Ca-125 and p16 and the presence of HPV (Human Papilloma Virus DNA 18. On examination of the hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the lesion replacing the cervix, endometrium and myometrium, revealed the same immunohistochemical findings observed on endometrial curettage and cervical biopsy specimens. Metastases were found in an ovarian cystic lesion and the lymph nodes. Conclusion With this report the authors have demonstrated that the spread of cervical adenocarcinoma to the uterine corpus, although rare, may be observed, and that in this instance immunohistochemical and molecular studies can provide sufficient information for accurate diagnosis even on small biopsy specimens.

  9. Novel monoclonal antibody against beta 1 integrin enhances cisplatin efficacy in human lung adenocarcinoma cells.

    Science.gov (United States)

    Kim, Min-Young; Cho, Woon-Dong; Hong, Kwon Pyo; Choi, Da Bin; Hong, Jeong Won; Kim, Soseul; Moon, Yoo Ri; Son, Seung-Myoung; Lee, Ok-Jun; Lee, Ho-Chang; Song, Hyung Geun

    2016-05-01

    The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial. Here, we developed a novel monoclonal antibody (mAb), called P5, by immunizing mice with human peripheral blood mononuclear cells (PBMC). Its anti-tumor effect is now being tested, in a clinical phase III trial, in combinatorial treatments with various chemical drugs. To confirm that P5 indeed binds to beta 1 integrin, cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb (TS2/16) and immunoblotted against P5 to reveal a 140 kDa molecular weight band, as expected. Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin. Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells, while causing inhibition of cell growth. When cells were co-treated with different concentrations of P5 mAb, the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner. Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30% increase in apoptosis, compared to baseline, and significantly more when compared to either the cisplatin or P5 alone group. The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed. Together, these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.

  10. Astragalus saponins induce apoptosis in human gastric adenocarcinoma cells via a caspase 3-dependent pathway

    Institute of Scientific and Technical Information of China (English)

    JOSHUA K S Ko; Kathy K W Auyeung

    2008-01-01

    Objective Many Asian countriea including China, Japan and Korea have very high incidence of gastric cancer, in which about 42 % cases occur in mainland China. The precise targets and underlying mechanisms are not well understood. Our previous study revealed that Astragalus saponins (AST) showed promising effects on the suppression of the growth of HT-29 human colon cancer cells and tumor xenograft by inhibiting cell proliferation and promoting apoptosis. In the present study, we investigated the anti-carcinogenic effects of AST in AGS human gastric adenocarcinoma cells and attempted to elucidate the underlying mechanisms. Methods Growth inhibition of AGS cells was determined by using the MTT viability test. Involvement of different members of the apoptotic cascade and other growth-related factors was explored by assessment of their protein expression using Western blot analysis. Distribution of cells in different phases of the cell cycle was assessed by flow eytometry. Results Our data indicate that AST induced growth-inhibition and apoptosis in AGS cells by activating caspase 3 with subsequent poly (ADP-ribose) polymerase (PARP) cleavage. Cell cycle arrest at the G2/M phase had been observed in AST-treated AGS cells. The anti-proliferative effect of AST was associated with modulation of eydin B1 and p21. We then demonstrate that AST could downregulate the expression of VEGF, of which interaction with its receptors is important for angiogenesis during tumor formation. Conclusions Our findings suggest that AST is an effective agent in gastric cancer treatment by inducing cell cycle arrest and apoptosis, of which anti-angiogenesis could be an alternative mode of action.

  11. Expression profiling of wild type and β-catenin gene disrupted human BxPC-3 pancreatic adenocarcinoma cells

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    Petter Angell Olsen

    2015-06-01

    Full Text Available To study the role of WNT/β-catenin signaling in pancreatic adenocarcinoma, human BxPC-3 cell lines deficient of the central canonical WNT signaling protein β-catenin were established by using zinc-finger nuclease mediated targeted genomic disruption of the β-catenin gene (CTNNB1. Comparison of the global transcription levels in wild type cells with two β-catenin gene disrupted clones identified 85 transcripts that were the most differentially regulated. Gene ontology (GO term enrichment analysis of these transcripts identified “cell adhesion” as the most significantly enriched GO term. Here we describe the data from the transcription profiling analysis published in the article “Implications of Targeted Genomic Disruption of β-Catenin in BxPC-3 Pancreatic Adenocarcinoma Cells” [1]. Data have been deposited to the Gene Expression Omnibus (GEO database repository with the dataset identifier GSE63072.

  12. Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells

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    Dunja Maria Baston-Buest

    2017-01-01

    Full Text Available Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1β, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface.

  13. AN ULTRASTRUTURAL STUDY OF HUMAN LUMINAL ENDOMETRIAL CELLS FOLLOWING DIFFERENT DOSES OF OESTROGEN REPLACEMENT THERAPY

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    SARANI SH.A

    2001-01-01

    Full Text Available Introduction: The effects of different doses of oestrogen on the endometrium of women with premature ovarian failure have been examined in this study. Materials and Methods: Four groups of women of reproductive age were studied; 1 normal fertile controls 2. patients given a standard, variable hormone replacement therapy (HRT 3. a group given a fixed daily dose of 1 mg of oestrogen and 4. a group given a fixed daily dose of 4 mg of oestrogen. Endrometrial diposises were taken at a bout 5-6 days after ovulation and tissue was prepared for light and electron microscopy. Morphometry was used to evaluate quantitatively various features of endometrial luminal epithelial cells. The volume fraction (Vv of nucleus to cell in the standard group was significantly larger than the 4 mg group. Results: The Vv of euchromatin to nucleus was larger in the controls and 4 mg group than the 1 mg subjects. The Vv of mitochondria to cell was largest in the control group. The ratio of desmosomes to surface membrane was increased (P<0.05 in the 1 mg subjects. Conclusion: These results suggest that, while standard HRT is generally a good mimic of controls, the 1 mg fixed dose delayed some membrane features and the fixed 4 mg group showed advancement in some organelle growth.

  14. Tetraploidization or autophagy: The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.

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    Borodkina, Aleksandra V; Shatrova, Alla N; Deryabin, Pavel I; Grukova, Anastasiya A; Nikolsky, Nikolay N; Burova, Elena B

    2016-01-01

    Previously we demonstrated that endometrium-derived human mesenchymal stem cells (hMESCs) via activation of the ATM/p53/p21/Rb pathway enter the premature senescence in response to oxidative stress. Down regulation effects of the key components of this signaling pathway, particularly ATM and p53, on a fate of stressed hMESCs have not yet been investigated. In the present study by using the specific inhibitors Ku55933 and Pifithrin-α, we confirmed implication of both ATM and p53 in H(2)O(2)-induced senescence of hMESCs. ATM or p53 down regulation was shown to modulate differently the cellular fate of H(2)O(2)-treated hMESCs. ATM inhibition allowed H(2)O(2)-stimulated hMESCs to escape the permanent cell cycle arrest due to loss of the functional ATM/p53/p21/Rb pathway, and induced bypass of mitosis and re-entry into S phase, resulting in tetraploid cells. On the contrary, suppression of the p53 transcriptional activity caused a pronounced cell death of H(2)O(2)-treated hMESCs via autophagy induction. The obtained data clearly demonstrate that down regulation of ATM or p53 shifts senescence of human endometrial stem cells toward tetraploidization or autophagy.

  15. Carbon metabolism of enterobacterial human pathogens growing in epithelial colorectal adenocarcinoma (Caco-2 cells.

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    Andreas Götz

    Full Text Available Analysis of the genome sequences of the major human bacterial pathogens has provided a large amount of information concerning their metabolic potential. However, our knowledge of the actual metabolic pathways and metabolite fluxes occurring in these pathogens under infection conditions is still limited. In this study, we analysed the intracellular carbon metabolism of enteroinvasive Escherichia coli (EIEC HN280 and EIEC 4608-58 and Salmonella enterica Serovar Typhimurium (Stm 14028 replicating in epithelial colorectal adenocarcinoma cells (Caco-2. To this aim, we supplied [U-(13C(6]glucose to Caco-2 cells infected with the bacterial strains or mutants thereof impaired in the uptake of glucose, mannose and/or glucose 6-phosphate. The (13C-isotopologue patterns of protein-derived amino acids from the bacteria and the host cells were then determined by mass spectrometry. The data showed that EIEC HN280 growing in the cytosol of the host cells, as well as Stm 14028 replicating in the Salmonella-containing vacuole (SCV utilised glucose, but not glucose 6-phosphate, other phosphorylated carbohydrates, gluconate or fatty acids as major carbon substrates. EIEC 4608-58 used C(3-compound(s in addition to glucose as carbon source. The labelling patterns reflected strain-dependent carbon flux via glycolysis and/or the Entner-Doudoroff pathway, the pentose phosphate pathway, the TCA cycle and anapleurotic reactions between PEP and oxaloacetate. Mutants of all three strains impaired in the uptake of glucose switched to C(3-substrate(s accompanied by an increased uptake of amino acids (and possibly also other anabolic monomers from the host cell. Surprisingly, the metabolism of the host cells, as judged by the efficiency of (13C-incorporation into host cell amino acids, was not significantly affected by the infection with either of these intracellular pathogens.

  16. Anti-tumor activity of CrTX in human lung adenocarcinoma cell line A549

    Institute of Scientific and Technical Information of China (English)

    Bin YE; Yan XIE; Zheng-hong QIN; Jun-chao WU; Rong HAN; Jing-kang HE

    2011-01-01

    Aim:To assess the cytotoxic effect of crotoxin (CrTX),a potent neurotoxin extracted from the venom of the pit viper Crotalus durissus terrificus,in human lung adenocarcinoma A549 cells and investigated the underlying mechanisms.Methods:A549 cells were treated with gradient concentrations of CrTX,and the cell cycle and apoptosis were analyzed using a flow cytometric assay.The changes of cellular effectors p53,caspase-3 and cleaved caspase-3,total P38MAPK and pP38MAPK were investigated using Western blot assays.A549 xenograft model was used to examine the inhibition of CrTX on tumor growth in vivo.Results:Treatment of A549 cells with CrTX (25-200 μg/mL) for 48 h significantly inhibited the cell growth in a dose-dependent manner (IC50=78 μg/mL).Treatment with CrTX (25 iJg/mL) for 24 h caused G1 arrest and induced cell apoptosis.CrTX (25 μg/mL) significantly increased the expression of wt p53,cleaved caspase-3 and phospho-P38MAPK.Pretreatment with the specific P38MAPK inhibitor SB203580 (5 μmol/L) significantly reduced CrTX-induced apoptosis and cleaved caspase-3 level,but G1 arrest remained unchanged and highly expressed p53 sustained.Intraperitoneal injection of CrTX (10 μg/kg,twice a week for 4 weeks) significantly inhibited A549 tumor xenograft growth,and decreased MVD and VEGF levels.Conclusion:CrTX produced significant anti-tumor effects by inducing cell apoptosis probably due to activation of P38MAPK and caspase-3,and by cell cycle arrest mediated by increased wt p53 expression.In addition,CrTX displayed anti-angiogenic effects in vivo.

  17. Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide

    Institute of Scientific and Technical Information of China (English)

    Mao-tao HUANG; Zhi-xin CHEN; Bing WEI; Bo ZHANG; Chun-hui WANG; Ming-hui HUANG; Rui LIU; Cheng-wei TANG

    2007-01-01

    Aim:To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide. Methods:Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemlcal staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drugactivated gene (NAG)-I was measured by RT-PCR. Results:Compared with the control and celecoxib groups,more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%±0.67%) was sig nificantly higher than that in the control group (6.23%±1.29%,P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05). Conclusion:Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.

  18. Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches

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    T. Jazedje

    2015-01-01

    Full Text Available The use of Mesenchymal Stromal Cells (MSCs aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1 coinjections of htMSCs and 4T1 murine tumor cell lineage and (2 injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 106 htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.

  19. Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas.

    Science.gov (United States)

    Li, Wenting; Wang, Ying; Fang, Xinzhi; Zhou, Mei; Li, Yiqun; Dong, Ying; Wang, Ruozheng

    2017-02-21

    BACKGROUND The aim of this study was to investigate the expression and the clinicopathologic significance of DNA methyltransferase 3B (DNMT3B), phosphatase and tensin homolog (PTEN) and human MutL homologs 1 (hMLH1) in endometrial carcinomas between Han and Uygur women in Xinjiang. MATERIAL AND METHODS The expression of DNMT3B, PTEN, and hMLH1 in endometrial carcinomas were assessed by immunohistochemistry, followed by an analysis of their relationship to clinical-pathological features and prognosis. RESULTS There were a 61.7% (95/154) overexpression of DNMT3B, 50.0% (77/154) loss of PTEN expression and 18.2% (28/154) loss of hMLH1 expression. The expression of DNMT3B and PTEN in endometrial carcinomas was statistically significantly different between Uygur women and Han women (p=0.001, p=0.010, respectively). DNMT3B expression was statistically significant based on the grade of endometrial carcinomas (p=0.031). PTEN loss was statistically significant between endometrioid carcinomas (ECs) and non endometrioid carcinomas (NECs) (p=0.040). DNMT3B expression was statistically significant in different myometrial invasion groups in Uygur women (p=0.010). Furthermore, the correlation of DNMT3B and PTEN expression was significant in endometrial carcinomas (p=0.021). PTEN expression was statistically significant in the overall survival (OS) rate of women with endometrial cancers (p=0.041). CONCLUSIONS Our findings suggest that PTEN and DNMT3B possess common regulation features as well as certain ethnic differences in expression between Han women and Uygur women. An interaction may exist in the pathogenesis of endometrial carcinoma. DNMT3B was expressed differently in cases of myometrial invasion and PTEN was associated with OS, which suggested that these molecular markers may be useful in the evaluation of the biological behavior of endometrial carcinomas and may be useful indicators of prognosis in women with endometrial carcinomas.

  20. The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas: a systematic review and meta-analysis.

    Science.gov (United States)

    Baandrup, Louise; Thomsen, Louise T; Olesen, Tina Bech; Andersen, Klaus Kaae; Norrild, Bodil; Kjaer, Susanne K

    2014-05-01

    The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association. The pooled HPV prevalence was estimated using a random effects model and the I(2) statistic was used to describe the amount of heterogeneity. Potential sources of heterogeneity were evaluated by meta-regression and stratified analyses. For the studies on adenocarcinomas including control tissue, random effects estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirty-seven studies were included. Among the 2630 adenocarcinomas, the pooled HPV prevalence was 11.2% (95% CI, 4.9-19.6%) with substantial between-study heterogeneity (I(2)=97.2%). The HPV prevalence varied by geographical region with highest prevalence in South America (45.1%, 95% CI, 21.9-69.4%), Asia (39.2%, 95% CI, 20.3-60.0%) and the Middle East (32.2%, 95% CI, 1.1-79.3%), and by detection method with the highest HPV prevalence in PCR-based studies. In the eight case-control studies, the pooled HPV prevalence was 36.8% (95% CI, 21.3-53.8%) in adenocarcinomas and 1.6% (95% CI, 0.0-9.6%) in controls giving an OR of 6.0 (95% CI, 2.0-17.9%) for the association between HPV and colorectal cancer. Among the 415 adenomas, the pooled HPV prevalence was 5.1% (95% CI, 0.0-17.8%; I(2)=93.7%). HPV may be associated with a subset of colorectal cancers. Future large-scale multicenter case-control studies with data on risk factors such as lifestyle and sexual behaviour are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells

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    Geng Y

    2016-07-01

    Full Text Available Ying Geng,1,* Lili Deng,2,* Dongju Su,1 Jinling Xiao,1 Dongjie Ge,3 Yongxia Bao,1 Hui Jing4 1Department of Respiratory, 2Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 3Department of Respiratory, The First Hospital of Harbin, 4Department of Emergency, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Background: Variations of microRNA (miRNA expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells.Materials and methods: Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis was evaluated.Results: In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A, and hsa-miR-622. Among them

  2. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

    Science.gov (United States)

    Guzeloglu Kayisli, Ozlem; Kayisli, Umit A; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J

    2015-01-01

    Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription

  3. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

    Directory of Open Access Journals (Sweden)

    Ozlem Guzeloglu Kayisli

    Full Text Available Use of long-acting progestin only contraceptives (LAPCs offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s in human endometrial stromal cells (HESCs. Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2 or E2+ medroxyprogesterone acetate (MPA or E2+ etonogestrel (ETO or E2+ progesterone (P4 were analyzed by quantitative Real-time (q-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA treated women and ovariectomized guinea pigs (GPs treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR

  4. Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b

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    Brosens Jan J

    2009-07-01

    Full Text Available Abstract Background Coordinated differentiation of the endometrial compartments in the second half of the menstrual cycle is a prerequisite for the establishment of pregnancy. Endometrial stromal cells (ESC decidualize under the influence of ovarian progesterone to accommodate implantation of the blastocyst and support establishment of the placenta. Studies into the mechanisms of decidualization are often hampered by the lack of primary ESC. Here we describe a novel immortalized human ESC line. Methods Primary ESC were immortalized by the transduction of telomerase. The resultant cell line, termed St-T1b, was characterized for its morphological and biochemical properties by immunocytochemistry, RT-PCR and immunoblotting. Its progestational response was tested using progesterone and medroxyprogesterone acetate with and without 8-Br-cAMP, an established inducer of decidualization in vitro. Results St-T1b were positive for the fibroblast markers vimentin and CD90 and negative for the epithelial marker cytokeratin-7. They acquired a decidual phenotype indistinguishable from primary ESC in response to cAMP stimulation. The decidual response was characterized by transcriptional activation of marker genes, such as PRL, IGFBP1, and FOXO1, and enhanced protein levels of the tumor suppressor p53 and the metastasis suppressor KAI1 (CD82. Progestins alone had no effect on St-T1b cells, but medroxyprogesterone acetate greatly enhanced the cAMP-stimulated expression of IGFBP-1 after 3 and 7 days. Progesterone, albeit more weakly, also augmented the cAMP-induced IGFBP-1 production but only after 7 days of treatment. The cell line remained stable in continuous culture for more than 150 passages. Conclusion St-T1b express the appropriate phenotypic ESC markers and their decidual response closely mimics that of primary cultures. Decidualization is efficiently induced by cAMP analog and enhanced by medroxyprogesterone acetate, and, to a lesser extent, by natural

  5. Effect of glucocorticoid on epidermal growth factor receptor in human salivary gland adenocarcinoma cell line HSG.

    Science.gov (United States)

    Kyakumoto, S; Kurokawa, R; Ota, M

    1990-07-12

    Human salivary gland adenocarcinoma (HSG) cells treated with 10(-6) M triamcinolone acetonide for 48 h exhibited a 1.7- to 2.0-fold increase in [125I]human epidermal growth factor (hEGF) binding capacity as compared with untreated HSG cells. Scatchard analysis of [125I]EGF binding data revealed that the number of binding sites was 83,700 (+/- 29,200) receptors/cell in untreated cells and 160,500 (+/- 35,500) receptors/cell in treated cells. No substantial change in receptor affinity was detected. The dissociation constant of the EGF receptor was 0.78 (+/- 0.26).10(-9) M for untreated cells, whereas it was 0.93 (+/- 0.31).10(-9)M for treated cells. The triamcinolone acetonide-induced increase in [125I]EGF binding capacity was dose-dependent between 10(-9) and 10(-6)M, and maximal binding was observed at 10(-6)M. EGF receptors on HSG cells were affinity-labeled with [125I]EGF by use of the cross-linking reagent disuccinimidyl suberate (DSS). The cross-linked [125I]EGF was 3-4% of the total [125I]EGF bound to HSG cells. The affinity-labeled EGF receptor was detected as a specific 170 kDa band in the autoradiograph after SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric analysis revealed that triamcinolone acetonide amplified the intensity of this band 2.0-fold over that of the band of untreated cells. EGF receptor synthesis was also measured by immunoprecipitation of [3H]leucine-labeled EGF receptor protein with anti-hEGF receptor monoclonal antibody. Receptor synthesis was increased 1.7- to 1.8-fold when HSG cells were treated with 10(-8)-10(-6)M triamcinolone acetonide for 48 h. When the immunoprecipitated, [35S]methionine-pulse-labeled EGF receptor was analyzed by SDS-PAGE and fluorography, the newly synthesized EGF receptor was detected at the position of 170 kDa; and treatment of HSG cells with triamcinolone acetonide resulted in a 2.0-fold amplification of this 170 kDa band. There was no significant difference in turnover rate of EGF receptor

  6. Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models.

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    Yong Sang Hong

    Full Text Available ERBB2-directed therapy is now a routine component of therapy for ERBB2-amplified metastatic gastroesophageal adenocarcinomas. However, there is little knowledge of the mechanisms by which these tumors develop acquired resistance to ERBB2 inhibition. To investigate this question we sought to characterize cell line models of ERBB2-amplified gastroesophageal adenocarcinoma with acquired resistance to ERBB2 inhibition. We generated lapatinib-resistant (LR subclones from an initially lapatinib-sensitive ERBB2-amplified esophageal adenocarcinoma cell line, OE19. We subsequently performed genomic characterization and functional analyses of resistant subclones with acquired lapatinib resistance. We identified a novel, acquired SrcE527K mutation in a subset of LR OE19 subclones. Cells with this mutant allele harbour increased Src phosphorylation. Genetic and pharmacologic inhibition of Src resensitized these subclones to lapatinib. Biochemically, Src mutations could activate both the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways in the lapatinib-treated LR OE19 cells. Ectopic expression of SrcE527K mutation also was sufficient to induce lapatinib resistance in drug-naïve cells. These results indicate that pathologic activation of Src is a potential mechanism of acquired resistance to ERBB2 inhibition in ERBB2-amplified gastroesophageal cancer. Although Src mutation has not been described in primary tumor samples, we propose that the Src hyperactivation should be investigated in the settings of acquired resistance to ERBB2 inhibition in esophageal and gastric adenocarcinoma.

  7. Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human fibroblasts and colon adenocarcinoma.

    Science.gov (United States)

    Hanif, Zahid; Ahmed, Farrukh R; Shin, Seung Won; Kim, Young-Kee; Um, Soong Ho

    2014-07-01

    A controlled preparation of cellulose nanocrystals of different sizes and shapes has been carried out by acid hydrolysis of microcrystalline cellulose. The size- and concentration-dependent toxicity effects of the resulting cellulose nanocrystals were evaluated against two different cell lines, NIH3T3 murine embryo fibroblasts and HCT116 colon adenocarcinoma. It could serve as a therapeutic platform for cancer treatment.

  8. Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers.

    NARCIS (Netherlands)

    Goethals, L.; Debucquoy, A.; Perneel, C.; Geboes, K.; Ectors, N.; Schutter, H. De; Penninckx, F.; McBride, W.H.; Begg, A.C.; Haustermans, K.

    2006-01-01

    PURPOSE: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intri

  9. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    , we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...

  10. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  11. The fatty acid beta-oxidation pathway is important for decidualization of endometrial stromal cells in both humans and mice.

    Science.gov (United States)

    Tsai, Jui-He; Chi, Maggie M-Y; Schulte, Maureen B; Moley, Kelle H

    2014-02-01

    Embryo implantation and development requires the endometrial stromal cells (ESCs) to undergo decidualization. This differentiation process requires glucose utilization, and blockade of the pentose phosphate pathway inhibits decidualization of ESCs both in vitro and in vivo. Glucose and fatty acids are energy substrates for many cell types, and fatty acid beta-oxidation is critical for embryo implantation. Here, we investigated whether beta-oxidation is required for decidualization of ESCs. As assessed by marker gene expression, decidualization of human primary ESCs was blocked by reducing activity of carnitine calmitoyltransferase I, the rate-limiting enzyme in beta-oxidation, either by short hairpin RNA-mediated silencing or by treatment with the inhibitor etomoxir. Ranolazine (RAN), a partial beta-oxidation inhibitor, blocked early decidualization of a human ESC line. However, decidualization resumed after several days, most likely due to a compensatory up-regulation of GLUT1 expression and an increase in glucose metabolism. Simultaneous inhibition of the beta-oxidation pathway with RAN and the pentose phosphate pathway with glucosamine (GlcN) impaired in vitro decidualization of human ESCs more strongly than inhibition of either pathway alone. These findings were confirmed in murine ESCs in vitro, and exposure to RAN plus GlcN inhibited decidualization in vivo in a deciduoma model. Finally, intrauterine implantation of time-release RAN and GlcN pellets reduced pup number. Importantly, pup number returned to normal after the end of the pellet-active period. This work indicates that both fatty acids and glucose metabolism pathways are important for ESC decidualization, and suggests novel pathways to target for the design of future nonhormonal contraceptives.

  12. Interferon-γ differentially modulates the impact of tumor necrosis factor-α on human endometrial stromal cells.

    Science.gov (United States)

    Spratte, Julia; Oemus, Anne; Zygmunt, Marek; Fluhr, Herbert

    2015-09-01

    The pro-inflammatory T helper (Th)-1 cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are immunological factors relevant at the feto-maternal interface and involved in the pathophysiology of implantation disorders. The synergistic action of the two cytokines has been described with regard to apoptotic cell death and inflammatory responses in different cell types, but little is known regarding the human endometrium. Therefore, we examined the interaction of TNF-α and IFN-γ in human endometrial stromal cells (ESCs). ESCs were isolated from specimens obtained during hysterectomy and decidualized in vitro. Cells were incubated with TNF-α, IFN-γ or signaling-inhibitor. Insulin-like growth factor binding protein (IGFBP)-1, prolactin (PRL), leukemia inhibitory factor (LIF), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted protein (RANTES) and monocyte chemotactic protein (MCP)-1 were measured using ELISA and real-time RT-PCR. Nuclear factor of transcription (NF)-κB and its inhibitor (IκBα) were analyzed by in-cell western assay and transcription factor assay. TNF-α inhibited and IFN-γ did not affect the decidualization of ESCs. In contrast, IFN-gamma differentially modulated the stimulating effect of TNF-alpha on cytokines by enhancing IL-6, RANTES and MCP-1 and attenuating LIF mRNA expression. These effects were time- and dose-dependent. IFN-γ had no impact on the initial activation of NF-κB signaling. Histone-deacetylase activity was involved in the modulating effect of IFN-γ on RANTES secretion. These observations showed a distinct pattern of interaction of the Th-1 cytokines, TNF-α and IFN-γ in the human endometrium, which could play an important role in the pathophysiology of implantation disorders.

  13. 4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

    OpenAIRE

    HUANG, QIN-MIAO; ZENG, YI-MING; ZHANG, HUA-PING; LV, LIANG-CHAO; YANG, DONG-YONG; LIN, HUI-HUANG

    2016-01-01

    The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expres...

  14. Preliminary studies of fluorescence image-guided photothermal therapy of human oesophageal adenocarcinoma in vivo using multifunctional gold nanorods

    Science.gov (United States)

    Nabavi, Elham; Singh, Mohan; Zhou, Yu; Gallina, Maria Elena; Zhao, Hailin; Ma, Daqing; Cass, Anthony; Hanna, George; Elson, Daniel S.

    2016-03-01

    We present a preliminary in vivo study of fluorescence imaging and photothermal therapy (PTT) of human oesophageal adenocarcinoma using multi-functionalised gold nanorods (GNRs). After establishing tumour xenograft in mouse functionalised GNRs were administrated intravenously (IV). Fluorescence imaging was performed to detect the tumour area. The intensity of the fluorescence signal varied significantly across the tumour site and surrounding tissues. PTT was then performed using a 808 nm continuous wave diode laser to irradiate the tumour for 3 minutes, inducing a temperature rise of ~44°C, which photothermally ablated the tumour.

  15. Changes in the transcriptome of the human endometrial Ishikawa cancer cell line induced by estrogen, progesterone, tamoxifen, and mifepristone (RU486 as detected by RNA-sequencing.

    Directory of Open Access Journals (Sweden)

    Karin Tamm-Rosenstein

    Full Text Available BACKGROUND: Estrogen (E2 and progesterone (P4 are key players in the maturation of the human endometrium. The corresponding steroid hormone modulators, tamoxifen (TAM and mifepristone (RU486 are widely used in breast cancer therapy and for contraception purposes, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiling of the human endometrial Ishikawa cancer cell line treated with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using RNA-sequencing. High levels of mRNA were detected for genes, including PSAP, ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers for endometrial biology were identified among E2 induced genes, and 93 among P4 responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and IL6ST, which are genes previously associated with endometrial receptivity. Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells, respectively, were also detected in two human mid-secretory endometrial biopsy samples. TAM treatment exhibited both antagonistic and agonistic effects of E2, and also regulated a subset of genes independently. The cell cycle regulator cyclin D1 (CCND1 showed significant up-regulation following treatment with TAM. RU486 did not appear to act as a pure antagonist of P4 and a functional analysis of RU486 response identified genes related to adhesion and apoptosis, including down-regulated genes associated with cell-cell contacts and adhesion as CTNND1, JUP, CDH2, IQGAP1, and COL2A1. CONCLUSIONS: Significant changes in gene expression by the Ishikawa cell line were detected after treatments with E2, P4, TAM, and RU486. These transcriptome data provide valuable insight into potential biomarkers related to endometrial receptivity, and also facilitate an understanding of the molecular changes that take place in the endometrium in the early stages of breast cancer treatment and contraception usage.

  16. Effects of tibolone and its metabolites on prolactin and insulin-like growth factor binding protein-1 expression in human endometrial stromal cells.

    Science.gov (United States)

    Guzel, Elif; Buchwalder, Lynn; Basar, Murat; Kayisli, Umit; Ocak, Nehir; Bozkurt, Idil; Lockwood, Charles J; Schatz, Frederick

    2015-05-01

    The effects of the postmenopausal replacement steroid tibolone and its 3α-, 3β-OH and Δ-4 tibolone metabolites were evaluated on progesterone receptor-mediated classic decidualization markers insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental cell incubations of confluent HESCs were subjected to ELISAs, Western blot analysis and RT/PCR, and results were statisically assesed. Over 21 days, specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin levels elicited by tibolone and its metabolites. Cultured HESCs were refractory to E2 and dexamethasone, whereas tibolone and each metabolite exceeded medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of cultured HESCs in evaluating the chronic effects of tibolone administration to women; (b) are consistent with PR-mediated endometrial atrophy and protection against endometrial bleeding despite the persistence of circulating ER-binding, but not PR-binding metabolites following tibolone administration to women.

  17. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha increased apoptosis of human endometrial cancer HEC-1A cells

    Directory of Open Access Journals (Sweden)

    Yang H

    2016-08-01

    Full Text Available Hui Yang, Rui Yang, Hao Liu, Zhongqian Ren, Cuicui Wang, Da Li, Xiaoxin Ma Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China Background: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α coactivates multiple transcription factors and regulates several metabolic processes. In this study, we focused on the roles of PGC-1α in the apoptosis of endometrial cancer HEC-1A cells. Materials and methods: PGC-1α expression in the HEC-1A cells was detected with real-time polymerase chain reaction and Western blot. Small interfering RNA directed against PGC-1α was designed and synthesized, and RNA interference technology was used to knock down PGC-1α mRNA and protein expression. Cell apoptosis, cell cycle, and mitochondrial membrane potential were then analyzed using flow cytometry. The expression of apoptotic proteins, Bcl-2 and Bax, was detected with Western blot. Results: The specific downregulation of PGC-1α expression in the HEC-1A cells increased their apoptosis through the mitochondrial apoptotic pathway by reducing the expression of Bcl-2 and increasing the expression of Bax. Conclusion: These results suggest that PGC-1α influences the apoptosis of HEC-1A cells and also provides a molecular basis for further investigation of the apoptotic mechanism in human endometrial cancer. Keywords: endometrial cancer, PGC-1α, apoptosis, Bcl-2, Bax

  18. Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer

    Science.gov (United States)

    Shimada, Hiroshi; Abe, Shyuetsu; Kohno, Takayuki; Satohisa, Seiro; Konno, Takumi; Takahashi, Syunta; Hatakeyama, Tsubasa; Arimoto, Chihiro; Kakuki, Takuya; Kaneko, Yakuto; Takano, Ken-ichi; Saito, Tsuyoshi; Kojima, Takashi

    2017-01-01

    Lipolysis-stimulated lipoprotein receptor (LSR) is a unique molecule of tricellular contacts of normal and cancer cells. We investigated how the loss of LSR induced cell migration, invasion and proliferation in endometrial cancer cell line Sawano. mRNAs of amphiregulin (AREG) and TEA domain family member 1 (TEAD1) were markedly upregulated by siRNA-LSR. In endometrial cancer tissues, downregulation of LSR and upregulation of AREG were observed together with malignancy, and Yes-associated protein (YAP) was present in the nuclei. siRNA-AREG prevented the cell migration and invasion induced by siRNA-LSR, whereas treatment with AREG induced cell migration and invasion. LSR was colocalized with TRIC, angiomotin (AMOT), Merlin and phosphorylated YAP (pYAP). siRNA-LSR increased expression of pYAP and decreased that of AMOT and Merlin. siRNA-YAP prevented expression of the mRNAs of AREG and TEAD1, and the cell migration and invasion induced by siRNA-LSR. Treatment with dobutamine and 2-deoxy-D-glucose and glucose starvation induced the pYAP expression and prevented the cell migration and invasion induced by siRNA-LSR. siRNA-AMOT decreased the Merlin expression and prevented the cell migration and invasion induced by siRNA-LSR. The loss of LSR promoted cell invasion and migration via upregulation of TEAD1/AREG dependent on YAP/pYAP and AMOT/Merlin in human endometrial cancer cells. PMID:28071680

  19. Nickel nanowires induced and reactive oxygen species mediated apoptosis in human pancreatic adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Kleve MG

    2011-07-01

    Full Text Available Md. Zakir Hossain1, Maurice G Kleve21Applied Biosciences (Bionanotechnology Research, Department of Applied Science, 2Molecular Biotechnology and Microscopy Laboratory, Department of Biology, University of Arkansas at Little Rock, Little Rock, Arkansas, USABackground: The ability to evade apoptosis is one of the key properties of cancer. The apoptogenic effect of nickel nanowires (Ni NWs on cancer cell lines has never been adequately addressed. Due to the unique physicochemical characteristics of Ni NWs, we envision the development of a novel anticancer therapeutics specifically for pancreatic cancer. Thus, we investigated whether Ni NWs induce ROS-mediated apoptosis in human pancreatic adenocarcinoma (Panc-1 cells. Methods: In this study Ni NWs were fabricated using the electrodeposition method. Synthesized Ni NWs were physically characterized by energy dispersive X-ray analysis, UV-Vis spectroscopy of NanoDrop 2000 (UV-Vis, magnetization study, scanning electron microscopy, and transmission electron microscopy. Assessment of morphological apoptotic characteristics by phase contrast microscopy (PCM, Ni-NWs-induced apoptosis staining with ethidium bromide (EB and acridine orange (AO followed by fluorescence microscopy (FM was performed. For molecular biological and biochemical characterization, Panc-1 cell culture and cytotoxic effect of Ni NWs were determined by using 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT assay. Quantitative apoptosis was analyzed by flow cytometry staining with propidium iodide through cell cycle arrest and generation of ROS using 2', 7'-dichlorofluorescein diacetate fluorescence intensity. In all experiments, Panc-1 cancer cells without any treatment were used as the negative controls.Results: The intracellular uptake of Ni NWs through endocytosis by Panc-1 cells was observed by PCM. EB and AO staining of FM and MTT assay qualitatively and quantitatively confirmed the extent of apoptosis. Flow

  20. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

    Directory of Open Access Journals (Sweden)

    Nacu Serban

    2011-01-01

    Full Text Available Abstract Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs, have been estimated using expressed sequence tag (EST libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal

  1. Correlation between Progesterone Dependent Cyclin G1 and PRA/PRB Expression in Endometrial Adenocarcinoma and the Related Clinical Significance%子宫内膜腺癌中孕激素依赖的cyclin G1与PRA/PRB表达的相关性及临床意义

    Institute of Scientific and Technical Information of China (English)

    方明; 于海礼; 袁东智; 徐倩; 张金虎; 何亚平; 岳利民

    2011-01-01

    Objective : To study the correlation hetween cyclin G1 and progesterone receptor isoforms PRA / PRB in endometrial adenocarcinoma in order to explore the reason for the low expression of cyclin G1 in this kind of disease. Methods : Immunohistochemistry was used to test the expression of cyclin G1 and progesterone receptor PRA / PRB in 48 cases of adenocarcinoma of endometrium including 17 cases of well-differentiated carcinoma, 19 cases of mid-differentiated carcinoma and 12 cases of poor-differentiated carcinoma. The correlation between cyclin G1 protein expression and PRA or PRB expression was analyzed. Results: In well. mid and poor differentiated adenocarcinoma of endometrium, PRA positive rates were 88. 2% ( 15/17 ), 79. 0% ( 15/19 ) and 66. 7%( 8/12 )respectively. Statistical analysis showed that there was no correlation between PRA expression and histological grade of endometrial adenocarcinoma( P>0. 05 ); PRB positive rates were 47. 1%( 8/17 ), 15. 8%( 3/19 )and 8. 3%( 1/12 ) respectively and cyclin G1 positive rates were 35. 3% ( 6/17 ), 10. 5% ( 2/19 ) and 0% ( 0/12 )respectively. The expression of both PRB and cyclin Gl were positively correlated with histological grade of endometrialadenocarcinoma( P < 0. 05 ). There was no correlation hetweencyclin G1 expression and PRA while relationship was found between cyclin G1 expression and PRB( P < 0. 05 ). Conclusion : In endometrial adenocarcinoma, the expressions of PRB and cyclin Gl protein decrease with the descending of tumor histological grade , and the expressions of both proteins are positively correlated. Thus it can be deduced that low expression of progesterone dependent cyclin G1 may he related to low expression of PRB in endometrial adenocarcinoma.%目的:探讨孕激素依赖的cyclin G1与孕激素受体亚型PRA和PRB在子宫内膜腺癌中表达的相关性及cyclin G1在子宫内膜腺癌中低表达的原因.方法:采用免疫组化SP法分别检测48例子宫内

  2. Clonal preservation of human pancreatic cell line derived from primary pancreatic adenocarcinoma.

    Science.gov (United States)

    Mohammad, R M; Li, Y; Mohamed, A N; Pettit, G R; Adsay, V; Vaitkevicius, V K; Al-Katib, A M; Sarkar, F H

    1999-11-01

    Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar genotypic properties. By using an automated DNA sequencer, a K-ras mutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-ras mutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 42,XY,add(3)(p11.2),der(7)t(7;12) (p22;q12),-10,-12,add (14)(p11),-18,add (20)(q13),-22/84, idemx2, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a

  3. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Bignotti Eliana

    2012-11-01

    Full Text Available Abstract Background Endometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC. Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes. Methods Trop-2 protein expression was quantified using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens from 118 patients who underwent surgical staging from 2001–9 by laparotomy for EEC. Clinicopathologic characteristics including age, stage, grade, lymphovascular space invasion, and medical comorbidities were correlated with immunostaining score. Univariate and multivariate analyses were performed for overall survival, disease-free survival, and progression-free survival in relation to clinical parameters and Trop-2 protein expression. Results Clinical outcome data were available for 103 patients. Strong Trop-2 immunostaining was significantly associated with higher tumor grade (p=0.02 and cervical involvement (p Conclusions Trop-2 protein overexpression is significantly associated with higher tumor grade and serves as an independent prognostic factor for DFS in endometrioid endometrial cancer.

  4. Trappin-2/elafin modulate innate immune responses of human endometrial epithelial cells to PolyI:C.

    Directory of Open Access Journals (Sweden)

    Anna G Drannik

    Full Text Available BACKGROUND: Upon viral recognition, innate and adaptive antiviral immune responses are initiated by genital epithelial cells (ECs to eradicate or contain viral infection. Such responses, however, are often accompanied by inflammation that contributes to acquisition and progression of sexually transmitted infections (STIs. Hence, interventions/factors enhancing antiviral protection while reducing inflammation may prove beneficial in controlling the spread of STIs. Serine antiprotease trappin-2 (Tr and its cleaved form, elafin (E, are alarm antimicrobials secreted by multiple cells, including genital epithelia. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated whether and how each Tr and E (Tr/E contribute to antiviral defenses against a synthetic mimic of viral dsRNA, polyinosine-polycytidylic acid (polyI:C and vesicular stomatitis virus. We show that delivery of a replication-deficient adenovector expressing Tr gene (Ad/Tr to human endometrial epithelial cells, HEC-1A, resulted in secretion of functional Tr, whereas both Tr/E were detected in response to polyI:C. Moreover, Tr/E were found to significantly reduce viral replication by either acting directly on virus or through enhancing polyI:C-driven antiviral protection. The latter was associated with reduced levels of pro-inflammatory factors IL-8, IL-6, TNFα, lowered expression of RIG-I, MDA5 and attenuated NF-κB activation. Interestingly, enhanced polyI:C-driven antiviral protection of HEC-Ad/Tr cells was partially mediated through IRF3 activation, but not associated with higher induction of IFNβ, suggesting multiple antiviral mechanisms of Tr/E and the involvement of alternative factors or pathways. CONCLUSIONS AND SIGNIFICANCE: This is the first evidence of both Tr/E altering viral binding/entry, innate recognition and mounting of antiviral and inflammatory responses in genital ECs that could have significant implications for homeostasis of the female genital tract.

  5. Collagen-coated nano-electrospun PCL seeded with human endometrial stem cells for skin tissue engineering applications.

    Science.gov (United States)

    Sharif, Shiva; Ai, Jafar; Azami, Mahmoud; Verdi, Javad; Atlasi, Mohammad Ali; Shirian, Sadegh; Samadikuchaksaraei, Ali

    2017-08-09

    Human endometrial stem cells (hEnSCs) are known as an attractive source of stem cells for regenerative medicine. hEnSCs are easily isolated and are capable of repairing uterine through their strong ability of creating new capillaries. In this study, a three-dimensional (3D) nanofibrous polycaprolactone (PCL)/collagen scaffold was fabricated and characterized in order to be applied as a new approach for skin reconstruction. Furthermore, the behavior of hEnSCs on this scaffold was investigated. First, a PCL 3D scaffold was constructed using electrospinning technique. Plasma treated and PCL was grafted by collagen. The constructs were characterized for mechanical and structural properties. Cell attachment, proliferation, viability, and differentiation of hEnSCs were assessed after being seeded on PCL and PCL/collagen scaffolds using scanning electron microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and real-time polymerase chain reaction tests. The results showed higher wettability for the PCL/collagen scaffold with desirable mechanical and structural characteristics compared to PCL and collagen alone. The attachment and proliferation rates of hEnSCs on the PCL/collagen scaffold were higher compared to those on the bare PCL. Hence, hEnSCs are newly discovered stem cell source for skin tissue engineering in vitro, particularly when developed on PCL/collagen nanofiber scaffolds. Therefore, application of hEnSCs for skin regeneration is a novel therapeutic approach for temporary skin substitute. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  6. Estrogen stimulates the proliferation of human endometrial cancer cells by stabilizing nucleophosmin/B23 (NPM/B23).

    Science.gov (United States)

    Chao, Angel; Lin, Chiao-Yun; Tsai, Chia-Lung; Hsueh, Swei; Lin, Ying-Yu; Lin, Cheng-Tao; Chou, Hung-Hsueh; Wang, Tzu-Hao; Lai, Chyong-Huey; Wang, Hsin-Shih

    2013-02-01

    Unopposed estrogen exposure is an important factor in the tumorigenesis of endometrial cancer. Nucleophosmin/B23 (NPM/B23), a phosphoprotein that has pleiotropic functions in cells, plays an important role in various cancers. However, the regulatory role of NPM/B23 in estrogen signaling in endometrial cancer has not been explored. Here, we report that NPM/B23 was required for estrogen-induced endometrial proliferation, and the increase in NPM/B23 was estrogen receptor α-dependent. Furthermore, estrogen increased NPM/B23 protein levels by repressing its ubiquitination and subsequently stabilizing the protein. The overexpression of the alternate reading frame (ARF) suppressed the estrogen-induced increase in the NPM/B23 protein levels, indicating that ARF inhibited the observed estrogen-mediated NPM/B23 stabilization. Our results suggest that one of the effects of estrogen on endometrial proliferation is the suppression of the NPM/B23-ARF interaction and the subsequent increase in NPM/B23 protein levels. This novel characterization of NPM/B23 in estrogen-mediated cell proliferation may extend our understanding of the tumorigenesis of steroid hormone-related cancers.

  7. Galectin-1 is overexpressed in CD133+ human lung adenocarcinoma cells and promotes their growth and invasiveness

    Science.gov (United States)

    Zhou, Xuefeng; Li, Dan; Wang, Xianguo; Zhang, Bo; Zhu, Hua; Zhao, Jinping

    2015-01-01

    Previous studies demonstrated that a subpopulation of cancer cells, which are CD133 positive (CD133+) feature higher invasive and metastatic abilities, are called cancer stem cells (CSCs). By using tumor cells derived from patients with lung adenocarcinoma, we found that galectin-1 is highly overexpressed in the CD133+ cancer cells as compared to the normal cancer cells (CD133−) from the same patients. We overexpressed galectin-1 in CD133− cancer cells and downregulated it in CSCs. We found that overexpression of galectin-1 promoted invasiveness of CD133− cells, while knockdown of galectin-1 suppressed proliferation, colony formation and invasiveness of CSCs. Furthermore, tumor growth was significantly inhibited in CSCs xenografts with knockdown of galectin-1 as compared to CSCs treated with scramble siRNAs. Biochemical studies revealed that galectin-1 knockdown led to the suppression of COX-2/PGE2 and AKT/mTOR pathways, indicating galectin-1 might control the phenotypes of CSCs by regulating these signaling pathways. Finally, a retrospective study revealed that galectin-1 levels in blood circulation negatively correlates with overall survival and positively correlates with lymph node metastasis of the patients. Taken together, these findings suggested that galectin-1 plays a major role on the tumorigenesis and invasiveness of CD133+ cancer cells and might serve as a potential therapeutic target for treatment of human patients with lung adenocarcinoma. PMID:25605013

  8. Selective gene therapy for human lung adenocarcinoma by tumor-specific expression of herpes simplex virus thymidine kinase gene

    Institute of Scientific and Technical Information of China (English)

    高振强; 高志萍; 张涛; 刘喜富

    1997-01-01

    According to the fact that CEA gene expressed only in lung adenocarcinoma but not in normal lung cells, a retroviral expression vector (pCEATK) of the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by CEA promoter was constructed and introduced into CEA-producing human lung adenocarcinoma cells GL and non-CEA-producing HeLa cells. The expression of pCEATK and Ganciclovir (GCV) sensitivity of the transfected cells were tested in vitro and in vivo . pCEATK expressed only in CEA-producing GL cells but not in non-CEA-producing HeLa cells. The sensitivity to GCV of pCEATK-transfected GL was 992 times higher compared with that of the parental cell line and there was obvious "bystander effect" in vitro. HeLa cells transfected wtih pCEATK were still resistant to GCV. Injection of GCV resulted in significant regression of pCEATK-transfected GL tumors in nude mice. In addition, all mice with any fraction of GL cells expressing HSV-TK exhibited a significant reduction in tumor growth, including mice

  9. TLR3 and TLR4 expression in healthy and diseased human endometrium

    Directory of Open Access Journals (Sweden)

    Kimmig Rainer

    2008-09-01

    Full Text Available Abstract Background Toll-like receptors (TLRs play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases. Methods TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3. The expression studies applied quantitative RT-PCR and immunolabelling of both proteins. Results TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3. Conclusion Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.

  10. Bisphenol A Alters β-hCG and MIF Release by Human Placenta: An In Vitro Study to Understand the Role of Endometrial Cells

    Directory of Open Access Journals (Sweden)

    C. Mannelli

    2014-01-01

    Full Text Available A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA. As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2 was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%. After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG and cytokine Macrophage Migration Inhibitory Factor (MIF. The results showed that direct exposure to BPA stimulated the release of both MIF and β-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

  11. Enhanced chemosensitivity of p73α gene transferred into H1299 cell line of human lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Yong; FAN Shi-zhi; Kalkunte S Srivenugopal; JIANG Yao-guang; QIN Chuan

    2004-01-01

    Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome;The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents ( 1.25 μmol/L of cDDP and 0.05 μmol/L of ADM)could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38.4% ( P < 0.01 ) and that of ADM from 12.1% to 49.3 % ( P < 0.01 ). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P < 0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.

  12. Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood

    Science.gov (United States)

    Zamay, Galina S; Kolovskaya, Olga S; Zamay, Tatiana N; Glazyrin, Yury E; Krat, Alexey V; Zubkova, Olga; Spivak, Ekaterina; Wehbe, Mohammed; Gargaun, Ana; Muharemagic, Darija; Komarova, Mariia; Grigorieva, Valentina; Savchenko, Andrey; Modestov, Andrey A; Berezovski, Maxim V; Zamay, Anna S

    2015-01-01

    Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics. PMID:26061649

  13. Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

    Science.gov (United States)

    Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A; Tsubura, Airo

    2016-05-01

    The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

  14. Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor gamma

    NARCIS (Netherlands)

    Alex, Sheril; Lange, Katja; Amolo, Tom; Grinstead, Jeffrey S.; Haakonsson, Anders K.; Szalowska, Ewa; Koppen, Arjen; Mudde, Karin; Haenen, Danielle; Al-Lahham, Sa'ad; Roelofsen, Han; Houtman, Rene; van der Burg, Bart; Mandrup, Susanne; Bonvin, Alexandre M. J. J.; Kalkhoven, Eric; Muller, Michael; Hooiveld, Guido J.; Kersten, Sander

    Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of

  15. Isolation and characterization of endometrial luminal epithelial and ...

    African Journals Online (AJOL)

    ADEYEYE

    2014-08-06

    Aug 6, 2014 ... reproductive capacity and health in animal and human subjects ... 2 et al., 2004). Animal model is not, however, without ... There are two main cell types in the endometrium, epithelia cells ... Of recent interest is the development of endometrial culture ... human endometrial cells and cell lines was constructed ...

  16. Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43

    Directory of Open Access Journals (Sweden)

    Xiaomiao Zhao

    2015-01-01

    Full Text Available Objects. To assess whether LNG exerts antiproliferation effects on human endometrial cells through changes of GJIC function and the phosphorylated Cx43. Methods. Cell proliferation and apoptosis of human endometrial stromal cells (HESCs and glandular cells (HEGCs treated with LNG in a dose- and time-dependent manner. GJIC change and further total Cx43 and serine 368 and 255 phosphorylated Cx43 were measured. Results. 5 × 10−5 mol/L LNG revealed a time-dependent inhibition of cell proliferation and an increase of apoptosis in both HESCs and HEGCs. Furthermore, these cells demonstrated a significant GJIC enhancement upon treatment with 5 × 10−5 mol/L for 48 hours. The effects of LNG were most noticeable in HESCs rather than in HEGCs. Associated with these changes, LNG induced a relative increase in total Cx43 in a time-dependent manner but not Ser368 phosphorylated Cx43. Moreover, laser scanning confocal microscope confirmed the increased expression of total Cx43 in the cytoplasm and, interestingly, the nuclear translocation of Ser255 phosphorylated Cx43. Conclusions. LNG likely inhibits the proliferation and promotes apoptosis in HESCs and HEGCs though an increase in gap junction permeability in vitro, which is achieved through the upregulation of Cx43 expression and the translocation of serine 255 phosphorylated Cx43 from the plasma to the nuclear compartment.

  17. Antitumor Effects and Biological Mechanism of Action of the Aqueous Extract of the Camptotheca acuminata Fruit in Human Endometrial Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chi-Shian Lin

    2014-01-01

    Full Text Available The aqueous extracts of the leaves and fruit of Camptotheca acuminata have long been used in traditional Chinese medicine (TCM for treating cancer patients. The chemotherapeutic drug, camptothecin (CPT, and related analogs were first isolated from C. acuminata in the 1970s. Although the antitumor effects of CPT have been characterized in recent years, the antitumor effects of aqueous extracts of C. acuminata have not been clarified. The aims of our current study were to determine the tumor-suppression efficiency of an aqueous extract of the fruit of C. acuminata (AE-CA in the human endometrial carcinoma cell lines, HEC-1A, HEC-1B, and KLE, and compare its antitumor effects with those of CPT. Cell viability assays indicated that a dosage of AE-CA containing 0.28 mg/mL of CPT demonstrated enhanced cytotoxicity, compared with CPT treatment. The effects of AE-CA on the induction of cell cycle arrest, the accumulation of cyclin-A2 and -B1, and the activation of caspase-3 and caspase-7 were similar to those of CPT. Furthermore, AE-CA exhibited a synergistic effect on the cytotoxicity of cisplatin in HEC-1A and HEC-1B cells. These results indicated that AE-CA is a potent antitumor agent and can be combined with cisplatin for the treatment of human endometrial cancer.

  18. Inhibition of Growth of Human Ileocecal Adenocarcinoma Cells HCT-8 and Inducing Apoptosis by Different RGD-containing Peptides

    Institute of Scientific and Technical Information of China (English)

    WANG Hua; YANG Shao-juan; GAO Shuo-hui; HUANG Yi-bing; LI Jing; CAI Ming-jun; XU Li; ZHANG Xue-zhong

    2008-01-01

    Human ileocecal adenocarcinoma cells HCT-8 were treated with RGD-containing cellular adhesion peptides including RGD,RGD(NH2)2(i.e.,RGE-NH2),RGDS,and RGDS-NH2,MTT assay was prepared to examine their inhibiting effects on HCT-8 cells after treatment,The methods including Haematoxylin and Eosin(HE) staining,transmission electron microscopy(TEM),immunohistochemistry,flow cytometry,and Reverse Transcription Polymerase Chain Reaction(RT-PCR) were used to observe the morphology of the apoptotic cells and analyze the mechanism of apoptosis,The experimental results indicate that RGD-containing cellular adhesion peptides can inhibit the growth and proliferation of tumor HCT-8 cells in a dose-dependent manner and induce the apoptosis of HCT-8 cells.At the same time,the high conservative property of RGD was confirmed again.

  19. Treatment Option Overview (Endometrial Cancer)

    Science.gov (United States)

    ... of endometrial cancer. Signs and symptoms of endometrial cancer include unusual vaginal bleeding or pain in the pelvis. These and other signs and symptoms may be caused by endometrial cancer or by other conditions. Check with your doctor ...

  20. Anti-proliferative effect of rhein, an anthraquinone isolated from Cassia species, on Caco-2 human adenocarcinoma cells.

    Science.gov (United States)

    Aviello, Gabriella; Rowland, Ian; Gill, Christopher I; Acquaviva, Angela Maria; Capasso, Francesco; McCann, Mark; Capasso, Raffaele; Izzo, Angelo A; Borrelli, Francesca

    2010-07-01

    In recent years, the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In this study, we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Cytotoxicity studies were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and trans-epithelial electrical resistance (TEER) assays whereas (3)H-thymidine incorporation and Western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Rhein (0.1-10 microg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 microg/ml) significantly reduced cell proliferation as well as mitogen-activated protein (MAP) kinase activation; by contrast, at high concentration (10 microg/ml) rhein significantly increased cell proliferation and extracellular-signal-related kinase (ERK) phosphorylation. Moreover, rhein (0.1-10 microg/ml): (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function; (ii) did not induce DNA damage, rather it was able to reduce H(2)O(2)-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and reactive oxygen species (ROS) levels induced by H(2)O(2)/Fe(2+). Rhein was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism that seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.

  1. Childhood body mass index and height and risk of histologic subtypes of endometrial cancer

    DEFF Research Database (Denmark)

    Aarestrup, J.; Gamborg, M.; Ulrich, L. G.

    2016-01-01

    BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer...... childhood ages. Height at all ages was statistically significant and positively associated with all endometrial cancers, except non-oestrogen-dependent cancers. At 7 years, per ~5.2 cm (1 z-score), the risk of endometrioid adenocarcinoma was 1.18 (95% confidence interval: 1.09-1.28). Among non......-users of unopposed oestrogens, associations between BMI and endometrioid adenocarcinoma strengthened, but no effects on height associations were observed. CONCLUSIONS: Endometrial carcinogenesis is linked to early-life body size, suggesting that childhood BMI and height may be useful indicators for the risk of later...

  2. Identifying candidate agents for lung adenocarcinoma by walking the human interactome

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-09-01

    Full Text Available Yajiao Sun,1 Ranran Zhang,2 Zhe Jiang,1 Rongyao Xia,1 Jingwen Zhang,1 Jing Liu,1 Fuhui Chen1 1Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 2Department of Respiratory, Harbin First Hospital, Harbin, People’s Republic of China Abstract: Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein–protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin. Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD. Keywords: lung adenocarcinoma, drug repositioning, bioinformatics, protein–protein interaction network, atracurium

  3. Dehydroepiandrosterone Inhibits Glucose Flux Through the Pentose Phosphate Pathway in Human and Mouse Endometrial Stromal Cells, Preventing Decidualization and Implantation

    OpenAIRE

    Frolova, Antonina I.; O'Neill, Kathleen; Moley, Kelle H.

    2011-01-01

    Endometrial stromal cells (ESC) must undergo a hormone-driven differentiation to form decidual cells as a requirement of proper embryo implantation. Recent studies from our laboratory have demonstrated that decidualizing cells require glucose transporter 1 expression and an increase in glucose use to complete this step. The present study focuses on the glucose-dependent molecular and metabolic pathways, which are required by ESC for decidualization. Inhibition of glycolysis had no effect on d...

  4. Induction of apoptosis by c9, t11-CLA in human endometrial cancer RL 95-2 cells via ERα-mediated pathway.

    Science.gov (United States)

    Wang, Jihui; Liu, Xiao; Zhang, Xiaojuan; Liu, Jing; Ye, Shuhong; Xiao, Shan; Chen, Hongzhou; Wang, Han

    2013-01-01

    Numerous studies have shown that conjugated linoleic acid (CLA) can inhibit cancer cells growth and induce apoptosis in vitro and in vivo. The aim of the present study was to investigate the effects of CLA, including cis9, trans11-conjugated linoleic acid (c9, t11-CLA) and trans10, cis12-conjugated linoleic acid (t10, c12-CLA), on apoptosis of human endometrial cancer RL 95-2 cells and its related mechanisms. The MTT analysis was used to evaluate the effect of CLA isomers on the viability of endometrial cancer RL 95-2 cells. We then estimated the apoptosis by Morphological observation and Annexin V-FITC/PI staining and flow cytometry. We also used Western blot analysis to assess the expression of caspase-3, Bax, Bcl-2 proteins and the activation of Akt/p-Akt and ERα/p-ERα. Propylpyrazole-triol (PPT), a selective ERα agonist was used to confirm the induction of apoptosis by c9, t11 CLA may relate to ERα-mediated pathway. In CLA-treated RL 95-2 cells, we found that c9, t11-CLA inhibited viability and trigged apoptosis, as judged from nuclear morphology and flow cytometric analysis. The expression of caspase-3 and the ratio of Bax/Bcl-2 were significant increased, but no obvious change was observed about Akt and p-Akt in c9, t11-CLA-treated cells. However, the expression of total ERα level in RL 95-2 cells-treated with c9, t11-CLA was unchanged, while in the concentration of 80 mM, c9, t11-CLA down-regulated the protein expression level of p-ERα. Then PPT has the antagonistic action on growth inhibitory effect in RL 95-2 cells incubated with c9, t11-CLA. This study demonstrated that c9, t11- CLA could induce apoptosis in RL 95-2 cells, and may involve in ERα-mediated pathway. These results indicated that c9, t11- CLA could induce apoptosis of endometrial cancer cells and may be potential agents for the treatment of endometrial cancer.

  5. Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)

    KAUST Repository

    Sarhan, Abbaa

    2013-10-17

    Objective: We have recently showed that MFGE8, a novel epithelial cell protein in the human endometrium, upregulated during the window of implantation. We hypothesized that MFGE8 may act as a key modulator of endometrial remodeling and trophoblast invasion. The aims of this study were (i) to investigate the in vitro regulation of human endometrial epithelial cells MFGE8 transcription, translation, and secretion by sex steroids and hCG; and (ii) to examine the possibility of MFGE8 secretion via microvesicles. Design: Experimental in vitro study using Ishikawa cells. Setting: University center. Interventions: Treatment with estradiol (E2), progesterone (P4), and human chorionic gonatropin (hCG). Main outcome measures: MFGE8 mRNA and protein expression, and identification of secreted microvesicles by mass spectrometry (MS) and immunoblotting. Results: E2, but not P4 or hCG, significantly upregulated MFGE8 mRNA expression. hCG significantly increased MFGE8 secretion. Microvesicels obtained after ultracentrifugation were visualized with atomic force microscopy ranging from ~100 to 200 nm. In addition to the expected 46 kD protein, the microvesicles contained a second form of secreted MFGE8 measuring ~30 kD which was confirmed by MS. Conclusions: We demonstrated (i) dual effects of E2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.

  6. Detection of chromosomal anomalies in endometrial atypical hyperplasia and carcinoma by using fluorescence in situ hybridization.

    Science.gov (United States)

    Qian, Junqi; Weber, Deena; Cochran, Richard; Hossain, Deloar; Bostwick, David G

    2010-04-25

    Endometrial cancer is the most common pelvic gynecological malignancy. The diagnosis of well-differentiated endometrial adenocarcinoma, atypical hyperplasia, and hyperplasia is often challenging. The authors sought to investigate the utility of chromosomal anomalies for the detection of endometrial hyperplasia and carcinoma using multitarget fluorescence in situ hybridization (FISH). Samples were collected by endometrial Tao brush and processed by liquid-based cytological preparation protocol from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 47 atypical hyperplasia, and 53 endometrial cancers. Each was hybridized using fluorescence-labeled DNA probes to chromosomes 1, 8, and 10. The FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on matched endometrial tissue samples. Numeric chromosomal anomalies were found in 0% (0 of 50) of benign, 20% (10 of 50) of hyperplasia, 74% (35 of 47) of atypical hyperplasia, and 87% (46 of 53) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 55% in cancer specimens, which was significantly higher than that in hyperplasia without atypia (13%, P chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma. Multitarget FISH appears to be useful for the differential diagnosis of hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, with a high level of sensitivity and specificity. It is also a potential tool for the early detection of neoplastic cells in endometrial cytology specimens. Endometrial hyperplasia with FISH-detected chromosomal anomalies may represent a clinically significant subset of cases that warrant close clinical follow-up. (c) 2010 American Cancer Society.

  7. Obesity and Endometrial Cancer.

    Science.gov (United States)

    Shaw, Eileen; Farris, Megan; McNeil, Jessica; Friedenreich, Christine

    Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and cancer risk, while severe obesity (BMI > 35 kg/m(2)) was associated with a 4.7-fold increase compared to normal-weight women (BMI cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.

  8. Analysis of 258 cases of uterine endometrial carcinoma in 18 years

    Energy Technology Data Exchange (ETDEWEB)

    Akutagawa, Noriyuki; Nishikawa, Akira; Saito, Tsuyoshi; Sagae, Satoru; Kudo, Ryuichi [Sapporo Medical Coll. (Japan)

    1999-12-01

    We investigated 258 cases of uterine endometrial cancer diagnosed and treated from 1980 through 1997 at our institution. Disease outcome, adjuvant therapies, and histologic features were analyzed. Patients' ages ranged from 20 to 90 years (mean, 57.0{+-}10.8 years). The 5-year survival rates were 97.5% for stage I disease, 81.7% for stage II disease, 69.8% for stage III disease, and 0% for stage IV disease. Patients with stage III disease who received both chemotherapy and radiation therapy as adjuvant therapies survive slightly, but not significantly, longer than did patients who received chemotherapy alone or radiation alone or no adjuvant therapy. The 136 patients (59.9%) with well-differentiated (G1) endometrioid carcinomas were significantly younger (mean age, 55.9{+-}10.3 years) than the 58 (25.6%) patients with moderately differentiated carcinomas (G2, 59.9{+-}10.4 years, p=0.01) and the 33 patients (14.5%) with poorly differentiated (G3, 59.9{+-}8.2 years, p=0.04) endometrioid carcinomas. The 60 cases of endometrial carcinoma from 1994 through 1997 were examined to determine whether endometrial hyperplasia and adenocarcinoma coexist. Endometrial hyperplasia was present in 23 (38%) of the 60 cases. The patients with both endometrial hyperplasia and adenocarcinoma were significantly younger (mean age, 47.7{+-}10.9 years) than the patients with endometrial adenocarcinoma alone (mean age, 59.5{+-}9.5 years, p<0.001). (author)

  9. Laminin production by human endometrial stromal cells relates to the cyclic and pathologic state of the endometrium

    DEFF Research Database (Denmark)

    Faber, M; Wewer, U M; Berthelsen, J G

    1986-01-01

    hyperplasia and adenocarcinomas did not react with antibody to laminin. The expression of laminin receptor in the stromal cells codistributed with laminin. Basement membranes of the surface epithelium, the glandular epithelium, and the vessels stained strongly with antibodies to laminin. In preneoplastic...

  10. Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma.

    Science.gov (United States)

    Grin, Andrea; Samaan, Sara; Tripathi, Monika; Rotondo, Fabio; Kovacs, Kalman; Bassily, Mena N; Yousef, George M

    2015-04-01

    Kallikreins are a family of serine proteases that are linked to malignancy of different body organs with potential clinical utility as tumor markers. In this study, we investigated kallikrein-related peptidase 6 (KLK6) and KLK10 expression in early gastroesophageal junction adenocarcinoma and Barrett esophagus (BE) with and without dysplasia. Immunohistochemistry revealed significantly increased KLK6 expression in early invasive cancer compared with dysplastic (P = .009) and nondysplastic BE (P = .0002). There was a stepwise expression increase from metaplasia to dysplasia and invasive tumors. Significantly higher KLK10 was seen in dysplastic lesions compared with metaplasia but not between dysplastic lesions and invasive cancers. KLK6 staining intensity was increased at the invasive front (P = .006), suggesting its role in tumor invasiveness. Neither KLK6 nor KLK10 was significantly associated with other prognostic markers, including depth of invasion, indicating their potential as independent biomarkers. Our results should be interpreted with caution due to limited sample size. There was a significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect. We then compared KLK6 and KLK10 messenger RNA expression between metaplastic and cancerous tissues in an independent data set of esophageal carcinoma from The Cancer Genome Atlas. KLK6 and KLK10 may be useful markers and potential therapeutic targets in gastroesophageal junction tumors.

  11. Loss of p27Kip1 expression in high grade human prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    MOHD ROHAIZAD MD. RODUAN

    2014-08-01

    Full Text Available p27Kip1 has been hypothesized to play a major role in carcinogenesis. Most of the published data reported that loss of p27Kip1 expression was strongly associated with development and progression of tumour. The purpose of this study was to analyze p27Kip1 expression in normal, benign and malignant prostate cancer tissues and their association with the clinicopathological parameters. The expression of p27Kip1 was evaluated by an immunohistochemistry method. p27Kip1 expression was significantly higher in normal and benign prostate tissues (P<0.01. In contrast, some malignant tissues had no p27Kip1 expression and most had weak p27Kip1 expression. p27Kip1 expression was found to be decreased significantly with increasing Gleason scores (P=0.003. Most of prostate adenocarcinomas (PCa with Gleason 8 and 9 showed loss of p27Kip1 expression. The expression was also positively correlated with prostate specific antigen level and age in PCa group (P=0.003 and 0.043 respectively, whereas no association was found between the p27Kip1 expression with tumour amount and age in benign prostatic hyperplasia group. This study suggests that loss of p27Kip1expression is essential during development and progression of prostate cancer.

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

    Science.gov (United States)

    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.

  13. Usefulness of sonohysterography in differentiating endometrial cancer from endometrial hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Kim, Min Jung; Ryu, Hee Sug [Aju University School of Medicine, Suwon (Korea, Republic of)

    1999-06-15

    To characterize the sonohysterographic (SH) findings of endometrial hyperplasia and cancer and to determine the role of SH in differentiating endometrial cancer from hyperplasia. The clinical, pathologic and SH findings of 38 patients with histologically confirmed endometrial hyperplasia (n=21), atypical hyperplasia 9n=6), and cancer (n=11) were reviewed retrospectively. We evaluate the presence and morphologic characteristics 9 surface contour ehcogenicity, echotexture) of endometrial thickening and mass, obliteration of endometrial cavity, and disruption of endometrial-myometrial interface on SH. SH findings of endometrial hyperplasia were endometrial thickening in 17 cases (81%), mass in 8 cases (38%), and regular surface of endometrium and mass in 16 (76%) and 6 cases (75%) respectively. Obliteration of endometrial cavity was seen only in 3 cases (14%) of endometrial hyperplasia and 1 case (17%) of atypical hyperplasia and disruption of endometrial-myometrial interface was not seen. Endometrial cancer showed endometrial thickening in 6 cases (55%), mass in 7 cases (64%), irregular surface of endometrium and mass in 10 (91%) and 7 cases (100%) respectively, obliteration of endometrial cavity in 10 cases(91%), and disruption of endometrial-myometrial interface in 4 of 8 cases with myometrial invasion. Using endometrial thickening or mass with irregular surface and obliteration of endometrial cavity as the positive findings for SH diagnosis of endometrial cancer, we observed sensitivity of 90.9%, specificity of 85.2%, and accuracy of 86.8%. The demonstration of the irregular surface with endometrial thickening or mass and obliteration of endometrial cavity through SH were suggestive of endometrial cancer.

  14. Expression and Correlation of GPR30 and EGFR in Endometrial Adenocarcinoma and Its Clinical Significance%G蛋白耦联受体30和表皮生长因子受体在子宫内膜腺癌中的表达

    Institute of Scientific and Technical Information of China (English)

    朱其舟; 舒宽勇

    2013-01-01

    the three groups was statistically significant (P0.05, respectively) but the type of histology, the expression of GPR30 with different tumor grade showed a significant statistical difference (P 0.05). In the EAC group, EGFR positive expression intensity correlated with FIGO stage, histopathological grade or tumor diameter (P0.05). Positively correlation between the expression of GPR30 and that of EGFR was observed in EAC group (r=0.308,P<0.05) Conclusions:GPR30 and EGFR probably have relationships with the occurrence and development of endometrial carcinoma. GPR30 and EGFR expression in endometrial adenocarcinoma was positively correlated with each other, there could be interaction between the two. GPR30 and EGFR could be more effective novel therapeutic targets of endometrial cancer.

  15. Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse

    Science.gov (United States)

    Vanichtantikul, Asama; Tharavichitkul, Ekkasit; Chitapanarux, Imjai

    2017-01-01

    Background. Uterine malignancy coexistent with pelvic organ prolapse (POP) is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.

  16. Transcriptome Analysis Reveals New Insights into the Modulation of Endometrial Stromal Cell Receptive Phenotype by Embryo-Derived Signals Interleukin-1 and Human Chorionic Gonadotropin: Possible Involvement in Early Embryo Implantation

    Science.gov (United States)

    Bourdiec, Amélie; Calvo, Ezequiel; Rao, C. V.; Akoum, Ali

    2013-01-01

    The presence of the conceptus in uterine cavity necessitates an elaborate network of interactions between the implanting embryo and a receptive endometrial tissue. We believe that embryo-derived signals play an important role in the remodeling and the extension of endometrial receptivity period. Our previous studies provided original evidence that human Chorionic Gonadotropin (hCG) modulates and potentiates endometrial epithelial as well as stromal cell responsiveness to interleukin 1 (IL1), one of the earliest embryonic signals, which may represent a novel pathway by which the embryo favors its own implantation and growth within the maternal endometrial host. The present study was designed to gain a broader understanding of hCG impact on the modulation of endometrial cell receptivity, and in particular, cell responsiveness to IL1 and the acquisition of growth-promoting phenotype capable of receiving, sustaining, and promoting early and crucial steps of embryonic development. Our results showed significant changes in the expression of genes involved in cell proliferation, immune modulation, tissue remodeling, apoptotic and angiogenic processes. This points to a relevant impact of these embryonic signals on the receptivity of the maternal endometrium, its adaptation to the implanting embryo and the creation of an environment that is favorable for the implantation and the growth of this latter within a new and likely hostile host tissue. Interestingly our data further identified a complex interaction between IL1 and hCG, which, despite a synergistic action on several significant endometrial target genes, may encompass a tight control of endogenous IL1 and extends to other IL1 family members. PMID:23717664

  17. Endometrial glands as a source of nutrients, growth factors and cytokines during the first trimester of human pregnancy: A morphological and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Jauniaux Eric

    2004-07-01

    Full Text Available Abstract Background The maternal circulation to the human placenta is not fully established until 10–12 weeks of pregnancy. During the first trimester the intervillous space is filled by a clear fluid, in part derived from secretions from the endometrial glands via openings in the basal plate. The aim was to determine the activity of the glands throughout the first trimester, and to identify components of the secretions. Methods Samples of human decidua basalis from 5–14 weeks gestational age were examined by transmission electron microscopy and immunohistochemically. An archival collection of placenta-in-situ samples was also reviewed. Results The thickness of the endometrium beneath the implantation site reduced from approximately 5 mm at 6 weeks to 1 mm at 14 weeks of gestation. The glandular epithelium also transformed from tall columnar cells, packed with secretory organelles, to a low cuboidal layer over this period. The lumens of the glands were always filled with precipitated secretions, and communications with the intervillous space could be traced until at least 10 weeks. The glandular epithelium reacted strongly for leukaemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, transforming growth factor beta, alpha tocopherol transfer protein, MUC-1 and glycodelin, and weakly for lactoferrin. As gestation advanced uterine natural killer cells became closely approximated to the basal surface of the epithelium. These cells were also immunopositive for epidermal growth factor. Conclusions Morphologically the endometrial glands are best developed and most active during early human pregnancy. The glands gradually regress over the first trimester, but still communicate with the intervillous space until at least 10 weeks. Hence, they could provide an important source of nutrients, growth factors and cytokines for the feto-placental unit. The endometrium may therefore play a greater role in regulating placental

  18. Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma and benign prostatic hyperplasia.

    Science.gov (United States)

    Hamdy, F. C.; Fadlon, E. J.; Cottam, D.; Lawry, J.; Thurrell, W.; Silcocks, P. B.; Anderson, J. B.; Williams, J. L.; Rees, R. C.

    1994-01-01

    Matrix metalloproteinase (MMP) expression was investigated in patients with prostatic adenocarcinoma and benign prostatic hyperplasia (BPH). Forty-one men were studied: 26 had histologically proven prostate cancer, with 14 (54%) showing metastatic disease; 15 patients had BPH. Prostatic tissue was obtained from transurethral resection and needle core biopsies; gelatinolytic activity was determined by zymography. Seven gelatinolytic bands were detected, with molecular weights ranging from > 100 kilodalton (kDa) to 29 kDa. Nine of 14 patients (64%) with skeletal metastases had 92 kDa activity, present in only two of 12 patients (17%) with a negative bone scan, and absent in BPH. The 92 kDa gelatinolytic activity was expressed in 73% of aneuploid tumours compared with 20% of diploid tumours. A 97 kDa gelatinase was expressed in 80% of BPH samples and 23% of carcinoma patients. Enzyme bands of 72, 66 and 45 kDa were equally expressed in malignant tissue, irrespective of metastatic status, but were expressed in fewer BPH patients. The 97, 92, 66 and 45 kDa enzymes were identified as being pro-MMP-9 sequences by Western blotting, using a specific antibody directed against the pro sequence of the mature protein. MMP activity appeared to be increased in malignant prostatic tissue compared with BPH. Pro-MMP-9, in its 92 kDa form, was shown to be exclusively expressed by malignant prostatic tissue, and in particular by tumours that exhibited the aggressive and metastatic phenotype. Images Figure 1 Figure 2 PMID:7506923

  19. LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans.

    Science.gov (United States)

    Tu, Ho-Chou; Schwitalla, Sarah; Qian, Zhirong; LaPier, Grace S; Yermalovich, Alena; Ku, Yuan-Chieh; Chen, Shann-Ching; Viswanathan, Srinivas R; Zhu, Hao; Nishihara, Reiko; Inamura, Kentaro; Kim, Sun A; Morikawa, Teppei; Mima, Kosuke; Sukawa, Yasutaka; Yang, Juhong; Meredith, Gavin; Fuchs, Charles S; Ogino, Shuji; Daley, George Q

    2015-05-15

    Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in Apc(Min/+) mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target. © 2015 Tu et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma.

    Science.gov (United States)

    Akbari, Abolfazl; Amanpour, Saeid; Muhammadnejad, Samad; Ghahremani, Mohammad Hossein; Ghaffari, Seyed Hamidollah; Dehpour, Ahmad Reza; Mobini, Gholam Reza; Shidfar, Fatemeh; Abastabar, Mahdi; Khoshzaban, Ahad; Faghihloo, Ebrahim; Karimi, Abbas; Heidari, Mansour

    2014-06-05

    Transforming growth factor-β (TGF-β) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-β pathway signaling via an inhibitor could be a valuable tool in CRC treatment. To evaluate the efficacy of systemic targeting of the TGF-β pathway for therapeutic effects on CRC, we investigated the effects of a TGβRI (TGF-β receptor 1) or TβRI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively. Our results showed no significant reduction in cell proliferation and vessel formation (170 ± 70 and 165 ± 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls. Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells.

  1. CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL PROFILE OF ENDOCERVICAL ADENOCARCINOMA

    Directory of Open Access Journals (Sweden)

    Arockiasamy Babiya Infant

    2016-07-01

    Full Text Available BACKGROUND Primary adenocarcinoma of cervix constitutes 10-15% of all cases of carcinoma of cervix, which is the second most common carcinoma next to squamous cell carcinoma. Endocervical adenocarcinoma have a considerable morphological overlap with endometrial adenocarcinoma though they differ in their aetiologies, behaviour, and treatments. This makes their diagnosis very difficult particularly in biopsy or curetting specimens or when a fractional dilation and curettage specimens show adenocarcinoma in both components of it. This study was done in the aim to suggest the possible origin of the tumour with the help of immunohistochemistry. AIMS AND OBJECTIVES To identify the incidence, distribution, clinicopathological, histomorphological features of endocervical adenocarcinomas and to determine the immunohistochemical expression of CEA, Vimentin, ER and PR in endometrioid type of adenocarcinoma detected in endocervical biopsies, fractional dilation and curettage specimens (Both the components showing similar morphology, and in hysterectomy specimens to suggest the site of origin of tumour. MATERIALS AND METHODS It is a retrospective descriptive study of cervical adenocarcinomas conducted in the Institute of Obstetrics and Gynaecology, Madras Medical College, Chennai for a period of 4 years during the period between 2009 November to 2013 October. The statistical analysis was performed using statistical package for social science software version 11.5 the clinicopathological profile of the tumour were calculated using Student t-test and chi-square test. OBSERVATION AND RESULTS Among the total 13499 cases received during the study period, 2489 were cervical malignancies comprising 148 adenocarcinoma. It includes 101 mucinous (Endocervical type, 44 endometrioid type, 2 serous type, and 1 clear cell type. Among the 30 cases of endometrioid type, 16 cases showed definite immunophenotype of cervical origin, 9 cases of endometrial origin and in the

  2. Type XV collagen in human colonic adenocarcinomas has a different distribution than other basement membrane zone proteins.

    Science.gov (United States)

    Amenta, P S; Briggs, K; Xu, K; Gamboa, E; Jukkola, A F; Li, D; Myers, J C

    2000-03-01

    In situ carcinomas must penetrate their own basement membrane to be classified as invasive, and subsequently infiltrate surrounding connective tissue and cross vascular basement membranes to metastasize hematogenously. Accordingly, in many studies, integral basement membrane components, including type IV collagen, laminin, and heparan sulfate proteoglycan, have been localized in a spectrum of tumors to gain insight into their role in neoplasia. A number of recently identified extracellular matrix molecules and isoforms of the aforementioned proteins have been localized to the basement membrane zone, illustrating another level of biochemical heterogeneity in these structures. As the complexity of these matrices becomes more apparent, their roles in maintaining homeostasis and in tumor biology falls into question. Of the new group of collagens localized to the basement membrane zone, type XV was the first to be characterized (Cell Tissue Res, 286:493-505, 1996). This nonfibrillar collagen has a nearly ubiquitous distribution in normal human tissues via a strong association with basement membrane zones, suggesting that it functions to adhere basement membrane to the underlying stroma. To begin investigation of this protein in malignant tumors, we have localized type XV in human colonic adenocarcinomas and compared its distribution with that of type IV collagen and laminin. Collagens XV and IV and laminin were found in all normal and colonic epithelial, muscle, fat, neural, and vascular basement membrane zones, as shown previously. In moderately differentiated, invasive adenocarcinomas, laminin and type IV collagen were sometimes observed as continuous, linear deposits around some of the malignant glands, but more often they were seen in either discontinuous deposits or were completely absent. In contrast, type XV collagen was characterized as virtually absent from the basement membrane zones of malignant glandular elements in moderately differentiated tumors

  3. hCG activates Epac-Erk1/2 signaling regulating Progesterone Receptor expression and function in human endometrial stromal cells.

    Science.gov (United States)

    Tapia-Pizarro, Alejandro; Archiles, Sebastián; Argandoña, Felipe; Valencia, Cecilia; Zavaleta, Keyla; Cecilia Johnson, M; González-Ramos, Reinaldo; Devoto, Luigi

    2017-06-01

    How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? hCG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cyclic AMP (cAMP) (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors. hCG signals through cAMP/protein kinase A (PKA) in gonadal cells, but in endometrial epithelial cells, hCG induces Erk1/2 activation independent of the cAMP/PKA pathway. Few data exist concerning the signal transduction pathways triggered by hCG in ESCs and their role in regulation of ESC function. This is an in vitro study comprising patients undergoing benign gynecological surgery (n = 46). Endometrial samples were collected from normal cycling women during the mid-secretory phase for ESCs isolation. The study conducted in an academic research laboratory within a tertiary-care hospital. The activation of the Erk1/2 signal transduction pathway elicited by hCG was evaluated in ESC. Signaling pathway inhibitors were used to examine the roles of PKA, PI3K, PKC, adenylyl cyclase and Epac on the hCG-stimulated up-regulation of phospho-Erk1/2 (pErk1/2). Erk1/2 phosphorylation was determined by immunoblot. siRNA targeting Epac was used to investigate the molecular mechanisms. To assess the role of Erk1/2 signaling induced by hCG on ESC function, gene expression regulation was examined by immunofluorescence and real-time quantitative PCR. The role of PR on the regulation of transcript levels was studied using progesterone and the PR antagonist RU486. All experiments were conducted using at least three different cell culture preparations in triplicate. Addition of hCG to ESCs in vitro induced the phosphorylation of Erk1/2 through cAMP accumulation. Such

  4. Therapeutic options for management of endometrial hyperplasia.

    Science.gov (United States)

    Chandra, Vishal; Kim, Jong Joo; Benbrook, Doris Mangiaracina; Dwivedi, Anila; Rai, Rajani

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

  5. Therapeutic options for management of endometrial hyperplasia

    Science.gov (United States)

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

  6. Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ

    DEFF Research Database (Denmark)

    Alex, Sheril; Lange, Katja; Amolo, Tom

    2013-01-01

    -chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, and transactivation assays, which show activation of PPARγ but not PPARα and PPARδ by SCFA. At concentrations required...... for PPARγ activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. Consistent...... with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPARγ. Our data...

  7. WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation.

    Science.gov (United States)

    Li, Quanxi; Kannan, Athilakshmi; Das, Amrita; Demayo, Franco J; Hornsby, Peter J; Young, Steven L; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

    2013-01-01

    Differentiation of endometrial stromal cells into decidual cells is a prerequisite for successful embryo implantation. Our previous studies in the mouse have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFβ superfamily, is essential for this differentiation process. BMP2 is markedly induced in human primary endometrial stromal cells (HESCs) as they undergo differentiation in response to steroid hormones and cAMP. The present study was undertaken to identify the BMP2-mediated molecular pathways in primary cultures of HESCs during decidualization. Using gene expression profiling, we identified wingless-related murine mammary tumor virus integration site 4 (WNT4) as a target of BMP2 regulation during decidualization. Attenuation of WNT4 expression in HESCs by small interfering RNA administration greatly reduced BMP2-induced stromal differentiation. Additionally, adenovirus-mediated overexpression of WNT4 in HESCs markedly advanced the differentiation program, indicating that it is a key regulator of decidualization. The stimulatory effect of WNT4 was accompanied by the accumulation of active β-catenin in the nuclei of decidualizing stromal cells, indicating the involvement of the canonical WNT signaling pathway. Functional inhibition of WNT4/β-catenin pathway by Dickkopf-1, an inhibitor of the canonical WNT signaling, or small interfering RNA-mediated silencing of β-catenin expression, greatly reduced the BMP2- and WNT4-induced decidualization. Gene expression profiling revealed that Forkhead box protein O1, a forkhead family transcription factor and previously reported regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. Taken together, these studies uncovered a linear pathway involving BMP2, WNT4/β-catenin, and Forkhead box protein O1 that operates in human endometrium to critically control decidualization.

  8. Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma.

    Science.gov (United States)

    Montalvo-Javé, Eduardo E; Olguín-Martínez, Marisela; Hernández-Espinosa, Diego R; Sánchez-Sevilla, Lourdes; Mendieta-Condado, Edgar; Contreras-Zentella, Martha L; Oñate-Ocaña, Luis F; Escalante-Tatersfield, Tomás; Echegaray-Donde, Agustín; Ruiz-Molina, Juan M; Herrera, Miguel F; Morán, Julio; Hernández-Muñoz, Rolando

    2016-04-01

    Gastric cancer is one of the main causes of global mortality. Here, reactive oxygen species (ROS) could largely contribute to gastric carcinogenesis. Hence, the present work was aimed to assess the role of ROS, oxidant status, NADPH oxidases (NOXs) expression, during human gastric adenocarcinoma. We obtained subcellular fraction from samples of gastric mucosa taken from control subjects (n = 20), and from 40 patients with gastric adenocarcinoma, as well as samples of distant areas (tumour-free gastric mucosa). Parameters indicative of lipid peroxidation and cell proliferation were selectively increased in both tumour-free and in cancerous gastric mucosa, despite of glutathione (GSH) content, glutathione reductase (GR) and superoxide dismutase (SOD) activities were increased in the adenocarcinoma. These high levels of antioxidant defences inversely correlated with down-regulated expression for NOX2 and 4; however, over-expression of NOX1 occurred with increased caspase-3 activity and overexpressed checkpoint 1 (MDC1) and cyclin D1 proteins. In the tumour-free mucosa an oxidant stress took place, without changing total GSH but with decreased activities for GR and mitochondrial SOD; moreover, over-expression of checkpoint 1 (MDC1) correlated with lower NOX2 and 4 expression in this mucosa. Chronically injured gastric mucosa increases lipoperoxidative events and cell proliferation. In the adenocarcinoma, cell proliferation was further enhanced, oxidant stress decreased which seemed to be linked to NOX1, MDC1 and cyclin D1 over-expression, but with a lower NOXs activity leading a 'low tone' of ROS formation. Therefore, our results could be useful for early detection and treatment of gastric adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Soluble Human Epidermal Growth Factor Receptor 2 (sHER2 as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Andre T. Baron

    2013-01-01

    Full Text Available Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2 for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81 and 7.93 (95% CI: 2.26, 27.82 greater for women and men with high sHER2 concentrations (≥6.60 ng/mL vs. low sHER2 concentrations (≤1.85 ng/mL, respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer.

  10. Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction.

    Science.gov (United States)

    Phillips, B E; Tubbs, R R; Rice, T W; Rybicki, L A; Plesec, T; Rodriguez, C P; Videtic, G M; Saxton, J P; Ives, D I; Adelstein, D J

    2013-04-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated.

  11. Production and radioimmunoimaging of novel fully human phage display recombinant antibodies and growth inhibition of lung adenocarcinoma cell line overexpressing Prx I.

    Science.gov (United States)

    Luo, Yi; Pang, Hua; Li, Shujie; Cao, Hui; Peng, Zhiping; Fan, Chunbo; Li, Shaolin

    2009-07-01

    The Peroxiredoxin I (Prx I) is a member of the Peroxiredoxin family, which is overexpressed in many diverse tumor types and is an anti-apoptosis protein for tumor cell proliferation and survival. Therapeutic strategies targeting the Prx I may therefore be effective broad-spectrum anticancer agents. We constructed a phage display single-chain variable fragment (scFv) antibody library and sieve out the fully human, lung adenocarcinoma-sepcific monoclonal antibodies. The selection on Prx I was performed using above-mentioned lung adenocarcinoma-sepcific monoclonal antibodies with high affinity to Prx I overexpressing lung adenocarcinoma cells. The candidate scFv sequences, based on enzyme-linked immunosorbent assay (ELISA) screening data, were chosen for soluble expression, and a 30 kDa band was observed on polyacrylamide gel electrophoresis as predicted. The purified antibodies were characterized by immunoblotting and showed high specificity to Prx I-overexpressing lung adenocarcinoma cells A549. Radioimmunoimaging was taken to evaluate specificity and distribution of antibodies in vivo. The radiolocalization index (RI) of tumor/serum and tumor/muscle gradually increased, reaching its peak (4.06 +/- 0.13 and 5.17 +/- 0.97, respectively) at 48 h postadministration. Single photon emission computed tomography (SPECT) imaging showed the radioactivity was aggregated in tumor locations and tumor imaging was clearly observed. The internalized scFv resulted in antibody-mediated cell apoptosis and downregulation of Prx I expression. These results demonstrate that the scFv possesses strong antitumor activity on lung adenocarcinoma and may therefore be an effective therapeutic candidate for the treatment of cancers that are dependent on Prx I for growth and survival.

  12. 7,12-Dimethylbenzanthracene induces apoptosis in RL95-2 human endometrial cancer cells: Ligand-selective activation of cytochrome P450 1B1

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Young [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Lee, Seung Gee [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Chung, Jin-Yong [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Kim, Yoon-Jae [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Park, Ji-Eun [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Oh, Seunghoon [Department of Physiology, College of Medicine, Dankook University, Cheonan 330-714 (Korea, Republic of); Lee, Se Yong [Department of Obstetrics and Gynecology, Busan Medical Center, Busan 611-072 (Korea, Republic of); Choi, Hong Jo [Department of General Surgery, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Yoo, Young Hyun, E-mail: yhyoo@dau.ac.kr [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); and others

    2012-04-15

    7,12-Dimethylbenzanthracene (DMBA), a polycyclic aromatic hydrocarbon, exhibits mutagenic, carcinogenic, immunosuppressive, and apoptogenic properties in various cell types. To achieve these functions effectively, DMBA is modified to its active form by cytochrome P450 1 (CYP1). Exposure to DMBA causes cytotoxicity-mediated apoptosis in bone marrow B cells and ovarian cells. Although uterine endometrium constitutively expresses CYP1A1 and CYP1B1, their apoptotic role after exposure to DMBA remains to be elucidated. Therefore, we chose RL95-2 endometrial cancer cells as a model system for studying DMBA-induced cytotoxicity and cell death and hypothesized that exposure to DMBA causes apoptosis in this cell type following CYP1A1 and/or CYP1B1 activation. We showed that DMBA-induced apoptosis in RL95-2 cells is associated with activation of caspases. In addition, mitochondrial changes, including decrease in mitochondrial potential and release of mitochondrial cytochrome c into the cytosol, support the hypothesis that a mitochondrial pathway is involved in DMBA-induced apoptosis. Exposure to DMBA upregulated the expression of AhR, Arnt, CYP1A1, and CYP1B1 significantly; this may be necessary for the conversion of DMBA to DMBA-3,4-diol-1,2-epoxide (DMBA-DE). Although both CYP1A1 and CYP1B1 were significantly upregulated by DMBA, only CYP1B1 exhibited activity. Moreover, knockdown of CYP1B1 abolished DMBA-induced apoptosis in RL95-2 cells. Our data show that RL95-2 cells are susceptible to apoptosis by exposure to DMBA and that CYP1B1 plays a pivotal role in DMBA-induced apoptosis in this system. -- Highlights: ► Cytotoxicity-mediated apoptogenic action of DMBA in human endometrial cancer cells. ► Mitochondrial pathway in DMBA-induced apoptosis of RL95-2 endometrial cancer cells. ► Requirement of ligand-selective activation of CYP1B1 in DMBA-induced apoptosis.

  13. Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor

    Institute of Scientific and Technical Information of China (English)

    Li-Fen Yu; Ying Cheng; Min-Min Qiao; Yong-Ping Zhang; Yun-Lin Wu

    2005-01-01

    AIM: To investigate the difference in activation of STAT3signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF).METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry.RESULTS: The expressions of phospho-STAT3 protein and constitutive activation of ST AT3 between two human stomach adenocarcinoma cell lines were different.Compared with the parental cell line SGC7901, the STAT3-DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line.CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.

  14. Integrin {beta}1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

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    Ishihara, Seiichiro [Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810 (Japan); Haga, Hisashi, E-mail: haga@sci.hokudai.ac.jp [Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810 (Japan); Yasuda, Motoaki [Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, N13-W7, Kita-ku, Sapporo 060-8586 (Japan); Mizutani, Takeomi; Kawabata, Kazushige [Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810 (Japan); Shirato, Hiroki [Department of Radiology, Hokkaido University Graduate School of Medicine, N15-W7, Kita-ku, Sapporo 060-8638 (Japan); Nishioka, Takeshi [Department of Biomedical Sciences and Engineering, Faculty of Health Sciences, Hokkaido University, N12-W5, Kita-ku, Sapporo 060-0812 (Japan)

    2010-06-04

    Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin {beta}1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin {beta}1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin {beta}1-dependent phenotype, and integrin {beta}1 might be a potentially effective therapeutic target in combination with radiotherapy.

  15. Dynamic Change of Polarity in Primary Cultured Spheroids of Human Colorectal Adenocarcinoma and Its Role in Metastasis.

    Science.gov (United States)

    Okuyama, Hiroaki; Kondo, Jumpei; Sato, Yumi; Endo, Hiroko; Nakajima, Aya; Piulats, Jose M; Tomita, Yasuhiko; Fujiwara, Takeshi; Itoh, Yu; Mizoguchi, Akira; Ohue, Masayuki; Inoue, Masahiro

    2016-04-01

    Intestinal epithelial cells possess apical-basal polarity, which governs the exchange of nutrients and waste. Perturbation of cell polarity appears to be a general feature of cancers, although most colorectal cancers are differentiated adenocarcinomas, in which polarity is maintained to some extent. Little is known about the role of dysregulated polarity in cancer. The cancer tissue-originated spheroid method was applied to the preparation and culture of spheroids. Spheroids were cultured in suspension or in type I collagen gel. Polarity was assessed by IHC of apical markers and electron microscopy. Two types of polarity status in spheroids were observed: apical-in, with apical membrane located at cavities inside the spheroids in type I collagen gel; and apical-out, with apical membrane located at the outermost layer of spheroids in suspension. These polarities were highly interchangeable. Inhibitors of Src and dynamin attenuated the polarity switch. In patients, clusters of cancer cells that invaded vessels had both apical-in and apical-out morphologic features, whereas primary and metastatic tumors had apical-in features. In a mouse liver metastasis model, apical-out spheroids injected into the portal vein became apical-in spheroids in the liver within a few days. Inhibitors of Src and dynamin significantly decreased liver metastasis. Polarity switching was observed in spheroids and human cancer. The polarity switch was critical in an experimental liver metastasis model.

  16. Use of the human colorectal adenocarcinoma (Caco-2) cell line for isolating respiratory viruses from nasopharyngeal aspirates.

    Science.gov (United States)

    Chan, K H; Yan, M K; To, K K W; Lau, S K; Woo, P C; Cheng, V C C; Li, W S; Chan, J F W; Tse, H; Yuen, K Y

    2013-05-01

    The human colorectal adenocarcinoma-derived Caco-2 cell line was evaluated as a means isolating common respiratory viruses from nasopharyngeal aspirates for the diagnosis of respiratory diseases. One hundred eighty-nine direct immunofluorescence positive nasopharyngeal aspirates obtained from patients with various viral respiratory diseases were cultured in the presence of Caco-2 cells or the following conventional cell lines: LLC-MK2, MDCK, HEp-2, and A549. Caco-2 cell cultures effectively propagated the majority (84%) of the viruses present in nasopharyngeal aspirate samples compared with any positive cultures obtained using the panel cells (78%) or individual cell line MDCK (38%), HEp-2 (21%), LLC-MK2 (27%), or A549 (37%) cell lines. The differences against individual cell line were statistically significant (P = viruses which were not cultivated in conventional cell lines. By contrast, 80% (24/30) of viruses not cultivated in Caco-2 cells were isolated using the conventional panel. The findings indicated that Caco-2 cells were sensitive to a wide range of viruses and can be used to culture a broad range of respiratory viruses.

  17. Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells by inducing cycle arrest and apoptosis.

    Science.gov (United States)

    Lv, Xue-Jiao; Zhao, Li-Jing; Hao, Yu-Qiu; Su, Zhen-Zhong; Li, Jun-Yao; Du, Yan-Wei; Zhang, Jie

    2015-01-01

    Lung cancer is the leading cause of cancer death in the world. Schizandrin B (Sch B) is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Sch B has multiple functions against cancer. The aim of this study was to determine the effect of Sch B on the proliferation, cell cycling, apoptosis and invasion of lung adenocarcinoma A549 cells by MTT, flow cytometry, wound healing and transwell invasion assays. Treatment with Sch B inhibited the proliferation of A549 cells in a dose-dependent manner. Sch B induced cell cycle arrest at G0/G1 phase by down-regulating the expression of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK6, but up-regulating p53 and p21 expression in A549 cells. Furthermore, Sch B triggered A549 cell apoptosis by increasing Bax, cleaved caspase-3, 9, Cyto C, but decreasing Bcl-2 and PCNA expression. In addition, Sch B inhibited the invasion and migration of A549 cells by down-regulating the expressions of HIF-1, VEGF, MMP-9 and MMP-2. Therefore, Sch B has potent anti-tumor activity and may be a promising traditional Chinese medicine for human lung carcinoma.

  18. Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Qiaoyun Zhou

    Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. [Study on the cell apoptosis induced by intracellular hyperthermia in human lung adenocarcinoma SPC-A1 cells].

    Science.gov (United States)

    Ma, Yongjie; Li, Hong; Yan, Zhubing; Gu, Hongchen

    2007-12-01

    This is a comparative study on the efficacy of differential cell apoptosis induced by three methods (intracellular hyperthermia, with water bath hyperthermia and extracellular hyperthermia) in human lung adenocarcinoma SPC-A1 cells in vitro. The effects of hyperthermia on cell apoptosis were determined by Transmission electron microscopy(TEM), agarose gel electrophoresis and flow cytometry methods, respectively. The intracellular effect of particle heating was compared with that of water bath hyperthermia and extracellular hyperthermia; significant differences between these heating methods were detected, the rate of apoptosis being 36.59%, 5.66%, 7.78% respectively. When treated with intracellular hyperthermia, the SPC-A1 cells manifested typical morphological characters of apoptosis by TEM observation, and the SPC-A1 cell DNA was degraded into large fragments by agarose gel electrophoresis assay. Our results showed that amino-silane Fe3O4 induced intracellular hyperthermia was superior to water bath hyperthermia and extracellular hyperthermia. It is mainly the interaction between intracellular nanoparticles and cell that induced apoptosis. Therefore, the aminosilane-coated Fe3O4 may be used in hyperthermia or chemotherapeutics on cancer cells for further clinical application.

  1. Antisense bcl-2 retrovirus vector increases the sensitivity of a human gastric adenocarcinoma cell line to photodynamic therapy.

    Science.gov (United States)

    Zhang, W G; Ma, L P; Wang, S W; Zhang, Z Y; Cao, G D

    1999-05-01

    The bcl-2 oncoprotein directly prolongs cellular survival by blocking apoptosis and its overexpression is associated with cellular resistance to killing by chemotherapeutic drugs and gamma-irradiation. Meanwhile, it has been shown that bcl-2 antisense oligonucleotide can induce apoptosis or increase toxicity of the treatment in tumors in vivo and in vitro. However, it is difficult to obtain stable transfection by this approach and there are no reports about the effect of an antisense bcl-2 on the sensitivity to oxidative stress induced by photodynamic therapy (PDT). Here we investigated the effect of an antisense bcl-2 RNA retrovirus vector transfer on the sensitivity of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization in a human gastric adenocarcinoma MGC803 cell line. The results indicate that antisense bcl-2-infected MGC803 cells expressed exogenous antisense bcl-2 mRNA measured by reverse transcription polymerase chain reaction and significantly reduced bcl-2 protein determined by western blotting analysis. The decreased expression of bcl-2 protein was accompanied by increased phototoxicity and susceptibility to apoptosis induced by 2-BA-2-DMHA PDT. Our finding suggests that reduction of bcl-2 protein in gastric cancers, and possibly also in a variety of other tumors, may be a novel and rational approach to improve photosensitivity and the treatment outcome.

  2. Cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells.

    Science.gov (United States)

    Lim, Young-Cheol; Yoo, Je-Ok; Kang, Seong-Sik; Kim, Young-Myeong; Ha, Kwon-Soo

    2011-03-01

    We investigated cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells. Cells were loaded with 0.5-10 μg/mL DH-II-24 for 12 h, and intracellular reactive oxygen species (ROS) and intracellular Ca(2+) levels, in situ tissue transglutaminase (tTGase) activity, cell viability, cell morphology and cell cycle were examined. DH-II-24 treatment had no effect on intracellular ROS production or cell morphology, and did not induce cell detachment at any concentrations tested. In addition, cell viability and cell cycle progression were not altered by the photosensitizer. However, DH-II-24 treatment elevated the basal level of intracellular Ca(2+) in a dose-dependent manner and inhibited tTGase activity without affecting tTGase expression levels. Furthermore, DH-II-24 inhibited lysophosphatidic acid-induced activation of tTGase in a dose-dependent manner. In contrast, photodynamic therapy (PDT) with 1 μg/mL DH-II-24 significantly elevated intracellular ROS and in situ tTGase activity in parallel with a rapid and large increase in intracellular Ca(2+) levels. DH-II-24-mediated PDT decreased cell viability and induced cell detachment. These results demonstrate that DH-II-24 treatment alone under darkness induced different cellular responses to DH-II-24-mediated PDT.

  3. The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells.

    Science.gov (United States)

    Friederichs, J; Zeller, Y; Hafezi-Moghadam, A; Gröne, H J; Ley, K; Altevogt, P

    2000-12-01

    Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a Mr 35,000-60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLex carbohydrate is essential for CD24-mediated rolling of tumor cells on P-selectin. To investigate the role of both antigens more closely, we transfected human A125 adenocarcinoma cells with CD24 and/or fucosyltransferase VII (Fuc TVII) cDNAs. Stable transfectants expressed CD24 and/or sialylLex. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLex. Only double transfectants showed rolling on P-selectin in vivo. When injected into mice, double transfectants arrested in the lungs, and this step was P-selectin dependent because it was strongly enhanced in lipopolysaccharide (LPS) pretreated wild-type mice but not in P-selectin knockout mice. CD24 modified by sialylLex was required on the tumor cells because the LPS-induced lung arrest was abolished by removal of CD24 from the cell surface by phosphatidylinositol-specific phospholipase C. A125-FucTVII single transfectants expressing sialylLex but not CD24 did not show P-selectin-mediated lung arrest. The sialylLex epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLex expression and clinical prognosis exist. Our data suggest an important role for sialylLex-modified CD24 in the lung colonization of human tumors.

  4. Selective gene transfer to endometrial cancer cells by a polymer against matrix metalloproteinase 2 (MMP-2).

    Science.gov (United States)

    Han, Joo Youn; Choi, Dong Soon; Kim, Changhoon; Joo, Hyun; Min, Churl K

    2008-04-01

    A novel cancer-cell-specific gene delivery vector with high transfection efficiency was designed and tested with an in vitro coculture consisting of the human endometrial adenocarcinoma cell line, HEC-1A cells, and normal endometrial stromal cells. For the cancer-cell targeting, polyethylenimine (PEI), a cationic polymer that can be easily combined with anionic DNA to form a particulate complex, polyplex, being capable of transferring a gene into a variety of cells, was covalently conjugated with antibodies against matrix metalloproteinase 2 (MMP-2), a typical surface-marker protein on cancer cells known for its close correlation with angiogenesis and invasion in many types of cancer, using the heterofunctional cross-linker, n-succinimidyl 3-(2-pyridyldithio)-propionamide. Biophysical properties and transfection efficiencies of anti-MMP-2-conjugated PEI were analyzed by means of dynamic light scattering, laser Doppler anemometry, and flow cytometry. Our results reveal that (1) the PEI-anti-MMP-2 antibody conjugate maintains physical parameters, including sizes and surface charges, which appear to be favorable for gene transfer and (2) when the pEGFP-N3 plasmid complexes of the PEI-anti-MMP-2 antibody conjugate are applied to the coculture consisting of HEC-1A cells and human stromal cells, a high level of green fluorescent protein expression occurs in HEC-1A cells over stromal cells, suggesting a specific gene transfer targeting cancer cells. Therefore, targeting invading cancer cells with the PEI-anti-MMP-2 antibody conjugate could be promising in endometrial cancer treatment, and this gene delivery system deserves further optimization in the context of targeted therapeutic gene delivery.

  5. In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gunassekaran, G.R., E-mail: gunassekaran@yahoo.co.in [Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu (India); Kalpana Deepa Priya, D.; Gayathri, R.; Sakthisekaran, D. [Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu (India)

    2011-08-12

    Highlights: {yields} Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. {yields} Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. {yields} In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. {yields} So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C{sub 30}H{sub 30}O{sub 8}, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in

  6. Hyperplasia and endometrial precancer

    Directory of Open Access Journals (Sweden)

    O. A. Gornikh

    2011-01-01

    Full Text Available Hyperplastic process is nothing but excessive proliferation determining by histological or cytological method. Extending of theprecancer" conception including not only atypical endometrial hyperplasia but also other pathological changes of the endometriu m (glandu- lar-cystic hyperplasia, polyposis, with the marked endocrine and metabolic disorders background is of some scientific interest and encour- ages a search for a wide range of hypothetical pathogenetic mechanisms and w ays to prevent precancer and endometrial cancer . However, such an extension of the view on the endometrial precancer is not an equivalent of the nosological diagnosis which involves anexact morpho- logic substrate of the pathological process and a specific treatment policy.

  7. Antigenotoxicity of probiotics and prebiotics on faecal water-induced DNA damage in human colon adenocarcinoma cells.

    Science.gov (United States)

    Burns, Anthony J; Rowland, Ian R

    2004-07-13

    Six strains of lactic acid producing bacteria (LAB) were incubated (1 x 10(8)cfu/ml) with genotoxic faecal water from a human subject. HT29 human adenocarcinoma cells were then challenged with the resultant samples and DNA damage measured using the single cell gel electrophoresis (comet) assay. The LAB strains investigated were Bifidobacterium sp. 420, Bifidobacterium Bb12, Lactobacillus plantarum, Streptococcus thermophilus, Lactobacillus bulgaricus and Enterococcus faecium. DNA damage was significantly decreased by all bacteria used with the exception of Strep. thermophilus. Bif. Bb12 and Lact. plantarum showed the greatest protective effect against DNA damage. Incubation of faecal water with different concentrations of Bif. Bb12 and Lact. plantarum revealed that the decrease in genotoxicity was related to cell density. Non-viable (heat treated) probiotic cells had no effect on faecal water genotoxicity. In a second study, HT29 cells were cultured in the presence of supernatants of incubations of probiotics with various carbohydrates including known prebiotics; the HT29 cells were then exposed to faecal water. Overall, incubations involving Lact. plantarum with the fructooligosaccharide (FOS)-based prebiotics Inulin, Raftiline, Raftilose and Actilight were the most effective in increasing the cellular resistance to faecal water genotoxicity, whereas fermentations with Elixor (a galactooligosaccharide) and Fibersol (a maltodextrin) were less effective. Substantial reductions in faecal water-induced DNA damage were also seen with supernatants from incubation of prebiotics with Bif. Bb12. The supernatant of fermentations involving Ent. faecium and Bif. sp. 420 generally had less potent effects on genotoxicity although some reductions with Raftiline and Elixor fermentations were apparent.

  8. Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung

    Directory of Open Access Journals (Sweden)

    Schwarzenbach Heidi

    2010-06-01

    Full Text Available Abstract Background Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line. Methods The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-ras, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp-/-/rag2-/- mice. Sensitivity towards chemotherapy was analysed by MTT assay. Results PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6, while others were detected for the first time (MEMO1, RIOK3. Specifically highly overexpressed genes (fold change > 10 were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp-/-/rag2-/- mice resulted in formation of primary tumors and spontaneous lung metastasis. Conclusion The established PaCa 5061 cell line and its injection into pfp-/-/rag2-/- mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease.

  9. Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies

    Science.gov (United States)

    Kristensen, C A; Askenasy, N; Jain, R K; Koretsky, A P

    1999-01-01

    Creatine (Cr) and cyclocreatine (cyCr) have been shown to inhibit the growth of a variety of human and murine tumours. The purpose of this study was to evaluate the anti-tumour effect of these molecules in relation to drug accumulation, energy metabolism, tumour water accumulation and toxicity. Nude mice carrying a human colon adenocarcinoma (LS174T) with a creatine kinase (CK) activity of 2.12 units mg−1 protein were fed Cr (2.5% or 5%) or cyCr (0.025%, 0.1% or 0.5%) for 2 weeks and compared with controls fed standard diet. Cr concentrations of 2.5% and 5% significantly inhibited tumour growth, as did 0.1% and 0.5% cyCr. In vivo 31P magnetic resonance spectroscopy (MRS) after 2 weeks of treatment showed an increase in [phosphocreatine (PCr)+phosphocyclocreatine (PcyCr)]/nucleoside triphosphate (NTP) with increasing concentrations of dietary Cr and cyCr, without changes in absolute NTP contents. The antiproliferative effect of the substrates of CK was not related to energy deficiency but was associated with acidosis. Intratumoral substrate concentrations (measured by 1H-MRS) of 4.8 μmol g−1 wet weight Cr (mice fed 2.5% Cr) and 6.2 μmol g−1 cyCr (mice fed 0.1% cyCr) induced a similar decrease in growth rate, indicating that both substrates were equally potent in tumour growth inhibition. The best correlant of growth inhibition was the total Cr or (cyCr+Cr) concentrations in the tissue. In vivo, these agents did not induce excessive water accumulation and had no systemic effects on the mice (weight loss, hypoglycaemia) that may have caused growth inhibition. © 1999 Cancer Research Campaign PMID:9888469

  10. Endometrial Cancer Screening

    Science.gov (United States)

    ... Transvaginal ultrasound Endometrial sampling Tests are used to screen for different types of cancer. Some screening tests ... endometrium by inserting a brush, curette , or thin, flexible tube through the cervix and into the uterus. ...

  11. Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples

    Institute of Scientific and Technical Information of China (English)

    Henrik Laurell; Louis Buscail; Michèle Bouisson; Philippe Berthelémy; Philippe Rochaix; Sébastien Déjean; Philippe Besse; Christiane Susini; Lucien Pradayrol; Nicole Vaysse

    2006-01-01

    AIM: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.METHODS: Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS: RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas.Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION: Expression profiling is a useful method to identify biomarkers and potential target genes.Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

  12. 骨桥蛋白在人胆囊腺癌中的表达%Expression of osteopontin in human gallbladder adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    刘开坤; 米泰宇; 李久澄; 贾海明; 张东生; 王平凡

    2012-01-01

    目的 应用抑制差减杂交联合cDNA芯片技术筛选人胆囊腺癌组织中差异表达基因,进一步探讨筛选出的骨桥蛋白在胆囊腺癌中的表达及作用.方法 胆囊腺癌组织和非肿瘤组织作为对比材料进行抑制差减杂交,构建正、反向差减杂交文库,应用差减片断的PCR产物制备cDNA芯片,筛选胆囊腺癌组织中差异表达基因.采用实时荧光定量技术和免疫组化方法验证和分析筛选出的胆囊腺癌中高表达基因骨桥蛋白在胆囊腺癌和正常胆囊组织中的转录水平和蛋白水平的表达.结果 成功构建了胆囊腺癌差减文库.cDNA芯片杂交结果显示骨桥蛋白在胆囊腺癌中高表达,经实时荧光定量技术证实.免疫组化结果表明骨桥蛋白在胆囊腺癌和癌旁胆囊组织中高表达,在正常胆囊组织中低表达(P<0.05),其表达部位主要在细胞核,在低分化胆囊腺癌中骨桥蛋白的表达有增高趋势.结论 抑制差减杂交方法构建的胆囊腺癌差减杂交文库富含胆囊腺癌差异表达基因.胆囊腺癌中高表达基因骨桥蛋白可能与胆囊细胞的生长、转移和侵袭能力有关.%Objective To examine the differential gene expressions between paracancerous gallbladder tissue and the human gallbladder adenocarcinoma (HGA) by suppression subtractive hybridization combined cDNA microarry and identification of the expression of osteopontin in HGA. Methods The differential gene expression subtracted cDNA library of paracancerous gallbladder tissue and HGA was constructed by suppression subtractive hybridization technique. The cDNA fragments of differentially expressed genes were prepared substrate of cDNA microarray. Based on the data of cDNA microarrays, which indicated an over-expression of osteopontin in human gallbladder adenocarcinoma, Real-time quantitative PCR and immunohistochemistry was used to identify and analyze the Transcription and protein expression levels of osteopontin in

  13. Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Yasuhiro [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Yoshida, Yukihiro [Department of Surgery, Asahi General Hospital, Chiba (Japan); Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Ishimine, Hisako [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan); Shinozaki-Ushiku, Aya [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Ito, Yoshimasa [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Sumitomo, Kenya [Department of Internal Medicine, JA Kochi Hospital, Kochi (Japan); Nakajima, Jun [Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Michiue, Tatsuo [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Asashima, Makoto, E-mail: asashi@bio.c.u-tokyo.ac.jp [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Life Science Center of Tsukuba Advanced Research Alliance (TARA), The University of Tsukuba, Tsukuba, Ibaraki (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan)

    2014-01-24

    Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

  14. Endometrioid Adenocarcinoma Metastatic to the Thyroid, Presenting Like Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Natasha Pollak

    2011-01-01

    Full Text Available Metastasis of uterine cancer to the head and neck is extremely rare. We report what we believe to be the first documented case of endometrioid adenocarcinoma metastasizing to the thyroid gland. An 80-year-old woman was referred to the otolaryngology service with a rapidly growing neck mass. The mass appeared to originate from the thyroid gland. Her clinical presentation was consistent with anaplastic thyroid carcinoma. A tracheostomy was performed. An open biopsy established the diagnosis of moderately differentiated adenocarcinoma, consistent with a gynecologic primary. The patient had undergone a hysterectomy 5 years prior for endometrioid adenocarcinoma. The thyroid tumor histology and immunophenotype corresponded well with her prior endometrial carcinoma, indicating that the thyroid mass was a metastasis from the endometrial primary. Radiotherapy appears to offer good local disease control in this rare case of endometrioid adenocarcinoma metastatic to the thyroid.

  15. Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis.

    Directory of Open Access Journals (Sweden)

    Kenji Unno

    Full Text Available Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Endometrial tumor tissue fragments (1.5 mm × 1.5 mm from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

  16. NAC1, a potential stem cell pluripotency factor expression in normal endometrium, endometrial hyperplasia and endometrial carcinoma.

    Science.gov (United States)

    Ishikawa, Masako; Nakayama, Kentaro; Yeasmin, Shamima; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Miyazaki, Kohji

    2010-05-01

    The purpose of this study was to investigate the role of NAC1 in the development of endometrial cancer. NAC1 expression and localization were assessed with immunohistochemistry in the normal cyclic human endometrium, hyperplastic endometrium, and endometrial cancer. Expression of NAC1 in the glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases, endometrial hyperplasia, and endometrial carcinoma. NAC1 expression was down-regulated during endometrial carcinogenesis. There were significant correlations between positive NAC1 expression and pathological grade (P=0.037). No significant associations were found between NAC1 expression and the other clinicopathological characteristics including patient age, FIGO staging, depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, menopause, or body mass index. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and JHEM2 cell lines, all of which overexpressed NAC1. Ectopic overexpression of the NAC1 gene stimulated cell proliferation in the HEC1B, and JHEM1 endometrial cancer cell lines, which have lower endogenous NAC1 expression. Endometrial carcinomas with NAC1 overexpression are clinically aggressive, high-grade carcinomas. Therefore, detection of NAC1 overexpression in endometrial cancers may identify patients who will benefit from NAC1 targeted therapy.

  17. Therapeutic efficacy evaluation of 111in-VNB-liposome on human colorectal adenocarcinoma HT-29/ luc mouse xenografts

    Science.gov (United States)

    Lee, Wan-Chi; Hwang, Jeng-Jong; Tseng, Yun-Long; Wang, Hsin-Ell; Chang, Ya-Fang; Lu, Yi-Ching; Ting, Gann; Whang-Peng, Jaqueline; Wang, Shyh-Jen

    2006-12-01

    The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and 111In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/ luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene ( luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm 3. The uptakes of 111In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm 3. The tumor/blood ratios of 111In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, 2.25 and 4.39, respectively, at 0, 5 and 10 mg/kg VNB. BLI showed that significant tumor control was achieved in the group of 10 mg/kg VNB ( 111In-VNB-liposome). WBAR also confirmed this result. In this study, we have demonstrated a non-invasive imaging technique with a luciferase reporter gene and BLI for evaluation of tumor treatment efficacy in vivo. The SCID mice bearing HT-29/ luc xenografts treated with 111In-VNB-liposome were shown with tumor reduction by this technique.

  18. Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.

    Science.gov (United States)

    Jhou, Bo-Yi; Song, Tuzz-Ying; Lee, Inn; Hu, Miao-Lin; Yang, Nae-Cherng

    2017-08-16

    NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.

  19. Sulforaphane down-regulates SKP2 to stabilize p27(KIP1) for inducing antiproliferation in human colon adenocarcinoma cells.

    Science.gov (United States)

    Chung, Yuan-Kai; Chi-Hung Or, Richard; Lu, Chien-Hsing; Ouyang, Wei-Ting; Yang, Shu-Yi; Chang, Chia-Che

    2015-01-01

    Sulforaphane is a cruciferous vegetable-derived isothiocyanate with promising chemopreventive and therapeutic activities. Induction of proliferation arrest and apoptosis principally contribute to sulforaphane's anticancer activity, but the precise molecular mechanisms remain elusive. The oncoprotein SKP2 is a key component of the SKP1-CULLIN1-F-box (SCF) E3 ligase complex and is responsible for directing SCF-mediated degradation of cyclin-dependent kinase inhibitor p27(KIP1) to promote cell proliferation. We herein provide the first evidence supporting the critical involvement of the SKP2-p27(KIP1) axis in sulforaphane-induced antiproliferation in various human colon adenocarcinoma cell lines. Specifically, sulforaphane markedly suppressed the levels of bromodeoxyuridine (BrdU) incorporation and clonogenicity in all tested cell lines, illustrating the antiproliferative effect of sulforaphane. Of note, sulforaphane-induced antiproliferation was accompanied with down-regulation of SKP2, leading to the stabilization and thus up-regulation of p27(KIP1). Additionally, sulforaphane was found to down-regulate SKP2 mainly through transcriptional repression, as sulforaphane lowered SKP2 mRNA expression and the SKP2 promoter activity. Furthermore, sulforaphane treatment led to the activation of both AKT and ERK, thus ruling out the possibility that sulforaphane down-regulates SKP2 by inhibiting AKT or ERK. Notably, sulforaphane-elicited suppression of BrdU incorporation and clonogenicity were significantly rescued in the context of SKP2 overexpression or p27(KIP1) depletion, therefore highlighting the important role of SKP2 down-regulation and the ensuing stabilization of p27(KIP1) in sulforaphane-induced antiproliferation. Collectively, these data expand our molecular understanding about how sulforaphane elicits proliferation arrest, but also implicate the application of sulforaphane in therapeutic modalities targeting SKP2. Copyright © 2014 The Society for Biotechnology

  20. [The effect and mechanism of endothelin-1-induced intracellular free calcium in human lung adenocarcinoma cells SPC-A1.].

    Science.gov (United States)

    Zhou, Juan; Zhang, Weimin; Ye, Qianjun; Jia, Gang

    2008-08-20

    Endothelin-1 (ET-1) is a potent mitogen involved in cell growth in human lung adenocarcinoma cells SPC-A1. The increase in intracellular free calcium ([Ca(2+)]i) plays a great role in this process. The aim of this study is to investigate the ET-1-induced [Ca(2+)]i responses in SPC-A1 cells and to explore its cellular mechanism. [Ca(2+)]i was measured by Fura-2/AM fluorescent assay. Endothelin receptors antagonists, calcium channel blockers and intracellular signal transduction blockers were used to study the underlying mechanism of ET-1-induced [Ca(2+)]i responses in SPC-A1 cells. At the concentration of 1*10(-15) mol/L-1*10(-8) mol/L, ET-1 caused a dose-dependent increase of [Ca(2+)]i in SPC-A1 cells (P 0.05), a highly selective endothelin receptor B (ETBR) antagonist. Depletion of extracellular Ca(2+) with free Ca(2+) solution and 0.1mmol/L ethyleneglycol bis (2-aminoethyl ether) tetraacetic acid (EGTA) or blockade of voltage dependent calcium channel with nifedipine at 1*10(-6) mol/L significantly reduced the ET-1-induced increase of [Ca(2+)]i. The ET-1-induced (1*10(-10) mol/L) increase of [Ca(2+)]i was also significantly attenuated by U73122 at 1*10(-5) mol/L (P <0.05), a phospholipase C inhibitor, and by Ryanodine at 50*10(-6) mol/L. However, Staurosporine (2*10(-9) mol/L), a protein kinas C inhibitor, exerted no significant effect on the ET-1-induced (1*10(-10) mol/L) increase of [Ca(2+)]i. ET-1 elevates [Ca(2+)]i via activation of ETA receptor. Both phospholipase C/Ca(2+) pathway and Ca(2+) influx through voltage dependent Ca(2+) channel activate by ETAR contribute to this process.

  1. Synergistic effects of tea polyphenols and ascorbic acid on human lung adenocarcinoma SPC-A-1 cells.

    Science.gov (United States)

    Li, Wei; Wu, Jian-xiang; Tu, You-ying

    2010-06-01

    Tea polyphenols have been shown to have anticancer activity in many studies. In the present study, we investigated effects of theaflavin-3-3'-digallate (TF(3)), one of the major theaflavin monomers in black tea, in combination with ascorbic acid (AA), a reducing agent, and (-)-epigallocatechin-3-gallate (EGCG), the main polyphenol presented in green tea, in combination with AA on cellular viability and cell cycles of the human lung adenocarcinoma SPC-A-1 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that the 50% inhibition concentrations (IC(50)) of TF(3), EGCG, and AA on SPC-A-1 cells were 4.78, 4.90, and 30.62 micromol/L, respectively. The inhibitory rates of TF(3) combined with AA (TF(3)+AA) and EGCG combined with AA (EGCG+AA) at a molar ratio of 1:6 on SPC-A-1 cells were 54.4% and 45.5%, respectively. Flow cytometry analysis showed that TF(3)+AA and EGCG+AA obviously increased the cell population in the G(0)/G(1) phase of the SPC-A-1 cell cycle from 53.9% to 62.8% and 60.0%, respectively. TF(3)-treated cells exhibited 65.3% of the G(0)/G(1) phase at the concentration of its IC(50). Therefore, TF(3)+AA and EGCG+AA had synergistic inhibition effects on the proliferation of SPC-A-1 cells, and significantly held SPC-A-1 cells in G(0)/G(1) phase. The results suggest that the combination of TF(3) with AA or EGCG with AA enhances their anticancer activity.

  2. Inhibitory and Cytotoxic Activities of Chrysin on Human Breast Adenocarcinoma Cells by Induction of Apoptosis

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Hasanzadeh, Malihe; Jabbari, Farahzad; Farkhondeh, Tahereh; Samini, Mohammad

    2016-01-01

    Objectives: Chrysin, an active natural bioflavonoid found in honey and many plant extracts, was first known for its antioxidant and anti-inflammatory effects. The fact that antioxidants have several inhibitory effects against different diseases, such as cancer, led to search for food rich in antioxidants. In this study, we investigated the antiproliferative and apoptotic effects of chrysin on the cultured human breast cancer cells (MCF-7). Materials and Methods: Cells were cultured in Roswell Park Memorial Institute medium and treated with different chrysin concentrations for three consecutive days. Cell viability was quantitated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The percentage of apoptotic cells was determined by flow cytometry using Annexin V-fluorescein isothiocyanate. Results: The MTT assay showed that chrysin had an antiproliferative effect on MCF-7 cells in a dose- and time-dependent manner. The 50% cell growth inhibition values for chrysin against MCF-7 cells were 19.5 and 9.2 μM after 48 and 72 h, respectively. Chrysin induced apoptosis in MCF-7 cells as determined by flow cytometry. Chrysin inhibits the growth of the breast cancer cells by inducing cancer cell apoptosis which may, in part, explain its anticancer activity. Conclusion: This study shows that chrysin could also be considered as a promising chemotherapeutic agent and anticancer activity in treatment of the breast cancer cells in future. SUMMARY Chrysin had an antiproliferative effect on human breast cancer cells (MCF-7) cells in a dose- and time-dependent mannerChrysin induced apoptosis in MCF-7 cells, as determined by flow cytometryChrysin inhibits the growth of the breast cancer cells by inducing cancer cell apoptosisChrysin may have anticancer activity. Abbreviations used: Human breast cancer cells (MCF-7), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), phosphate-buffered saline (PBS), normal fibroblast mouse (L929).

  3. Uterine/Endometrial Cancer: Chemotherapy

    Science.gov (United States)

    ... Types of Gynecologic Cancers Uterine/Endometrial Cancer Chemotherapy Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected ...

  4. General Information About Endometrial Cancer

    Science.gov (United States)

    ... Screening Research Endometrial Cancer Treatment (PDQ®)–Patient Version General Information About Endometrial Cancer Go to Health Professional ... the cervix , which leads to the vagina . Enlarge Anatomy of the female reproductive system. The organs in ...

  5. Human Equilibrative Nucleoside Transporter 1 (hENT1 in Pancreatic Adenocarcinoma: Towards Individualized Treatment Decisions

    Directory of Open Access Journals (Sweden)

    Jennifer L. Spratlin

    2010-12-01

    Full Text Available Pancreatic cancer is one of the most lethal cancers, where curative surgical resections are rare and less than 5% of patients experience long-term survival. Despite numerous clinical trials, improvements in the systemic treatment of this disease have been limited. Gemcitabine, a nucleoside analogue, is still considered the standard of care chemotherapy for most patients in the advanced disease setting. To exert its cytotoxic effects, gemcitabine must enter cells via nucleoside transporters, most notably human equilibrative nucleoside transporter 1 (hENT1. Increasingly strong evidence suggests hENT1 is a prognostic biomarker in gemcitabine-treated pancreatic cancer, and may well be a predictive biomarker of gemcitabine efficacy. In this review, we synthesize the literature surrounding hENT1 in pancreatic cancer, identify the key outstanding questions, and suggest strategies to prospectively evaluate the clinical utility of hENT1 in future clinical studies.

  6. Ezh2、Runx3和caspase-3在子宫内膜样腺癌中的表达及相关性%Expression and relationship of Ezh2, Runx3 and caspase-3 in endometrial adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    郭真理; 陈柯; 王晓秋; 胡闻

    2011-01-01

    目的 探讨Ezh2、Runx3和caspase-3在正常子宫内膜、子宫内膜增殖症和子宫内膜样腺癌组织中的表达及相关性.方法 采用组织芯片技术和免疫组织化学SP法检测30例正常子宫内膜组织、30例单纯性增生内膜、30例复杂伴不典型增生内膜、72例子宫内膜样腺癌组织中Ezh2、Runx3和caspase-3蛋白的表达.结果 Ezh2、Runx3和caspase-3蛋白在子宫内膜样腺癌组织中的阳性表达率分别为83.3%(60/72)、26.4%(19/72)、33.3%(24/72);Ezh2在腺癌组织中的阳性率明显高于正常和各型增生内膜(16.7%、33.3%、63.3%;P0.05);caspase-3的阳性表达与组织分级有关(P0.05).Ezh2与Runx3的蛋白表达呈负相关(rs=-0.262,P0.05). Positive expression of caspase-3 protein was related to the histological grade(P0.05). The expression of Ezh2 protein was negatively correlated to that of Runx3 (rs=-0.262, P<0.05). Conclusions Abnormal expression of Ezh2, Runx3 and caspase-3 proteins is associated with the development and progression of endometrioid adenocarcinoma. Combined analysis of Ezh2, Runx3 and caspase-3 may offer prognostic information for patients with endometrial cancer.

  7. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  8. CytoregR inhibits growth and proliferation of human adenocarcinoma cells via induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Hassanhi M

    2006-01-01

    Full Text Available Abstract Background Cancer is one of the devastating neovascular diseases that incapacitate so many people the world over. Recent reports from the National Cancer Institute indicate some significant gain therapy and cancer management as seen in the increase in the 5-year survival rate over the past two decades. Although near-perfect cure rate have been reported in the early-stage disease, these data reveal high recurrence rate and serious side effects including second malignancies and fatalities. Most of the currently used anticancer agents are only effective against proliferating cancer cells. Thus attention has been focused on potential anti-cancer agents capable of killing cancer cells independent of the cell cycle state, to ensure effective elimination of most cancer cells. The objective of this study was to test the chemosensitivity and potential mechanism of action of a novel cancer drug, CytoregR, in a panel of human cancer cells. Methods the study was performed using a series of bioassays including Trypan blue exclusion, MTS Growth inhibition, LDH-cytotoxicity, TUNEL-Terminal DNA fragmentation Apoptosis Assay, and the Caspase protease CPP32 activity assays. Results CytoregR induced significant dose- and time-dependent inhibition of growth in all the cells; with significant differences in chemosensitivity (P < 0.05 between the target cells becoming more apparent at 48 hr exposure. CytoregR showed no significant effect on normal cells relative to the tumor cells. Growth inhibition in all the cells was due to induction of apoptosis at lower concentrations of cytoregR (> 1:300. CytoregR-induced caspase protease-3 (CPP32 activation significantly and positively correlated with apoptosis induction and growth inhibition; thus implicating CPP32 as the principal death pathway in cytoregR-induced apoptosis. Conclusion CytoregR exerted a dose-and time-dependent growth inhibitory effect in all the target cells through induction of apoptosis via the

  9. Procyanidin B2 cytotoxicity to MCF-7 human breast adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Monalisa M Avelar

    2012-01-01

    Full Text Available Procyanidins have attracted some attention due to their demonstrated chemopreventive action, a relatively new and promising strategy to prevent cancer. Breast cancer is one of the leading causes of death in women worldwide and its treatment needs improvements. The aim of this work was to verify the procyanidin dimmer B2 cytotoxic effect to MCF-7 human breast cancer cells. MCF-7 cells were cultured in RPMI medium, containing 20% fetal bovine serum and antibiotics in a CO 2 chamber. The cells were treated with different concentrations of B2 and its cytotoxic potential was assessed by the sulforhodamine B assay, morphologically through haematoxylin-eosin staining and by DNA fragmentation analysis. The significance of differences between experimental conditions was determined using the ANOVA test, followed by the Tukey test when P<0.05. Cell proliferation decreased in a concentration and time-dependent manner upon procyanidin dimmer B2 treatment, being 19.20 μM the IC 50 . Procyanidin dimmer B2 treatment displayed concentration and time-dependent decline in MCF-7 cells compared to control and also induced morphological alterations compatible with cell-death induction. Cell condensation and cell diameter decreased (3.5 folds compared to control cells, after 48 h cell-exposure to 50 μM procyanidin dimmer B2, but the DNA ladder formation was not observed. In conclusion, our results demonstrated that procyanidin dimmer B2 exhibits cytotoxic activity to MCF-7 cells and it could be a potential antineoplastic agent. Further studies are necessary to clarify the procyanidin dimmer B2 mechanism of action. The evaluation of biological efficacy of individual components is an important step towards drug discovery and development.

  10. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    Science.gov (United States)

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types.

  11. In vitro cytotoxicity of silver nanoparticles and zinc oxide nanoparticles to human epithelial colorectal adenocarcinoma (Caco-2) cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yijuan [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018 (China); Guan, Rongfa, E-mail: rongfaguan@163.com [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018 (China); Lyu, Fei [Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014 (China); Kang, Tianshu; Wu, Yihang [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018 (China); Chen, Xiaoqiang [Hubei University of Technology, Wuhan 430068 (China)

    2014-11-15

    Highlights: • The characterization of Ag NPs and ZnO NPs. • The various morphologies of Caco-2 cells stained with AO/EB. • The viability of Caco-2 cells after Ag NPs and ZnO NPs exposure. • The cytotoxicity of Ag NPs and ZnO NPs on Caco-2 cells by oxidative stress assays. - Abstract: With the increasing applications of silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) in foods and cosmetics, the concerns about the potential toxicities to human have been raised. The aims of this study are to observe the cytotoxicity of Ag NPs and ZnO NPs to human epithelial colorectal adenocarcinoma (Caco-2) cells in vitro, and to discover the toxicity mechanism of nanoparticles on Caco-2 cells. Caco-2 cells were exposed to 10, 25, 50, 100, 200 μg/mL of Ag NPs and ZnO NPs (90 nm). AO/EB double staining was used to characterize the morphology of the treated cells. The cell counting kit-8 (CCK-8) assay was used to detect the proliferation of the cells. Reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione (GSH) assay were used to explore the oxidative damage of Caco-2 cells. The results showed that Ag NPs and ZnO NPs (0–200 μg/mL) had highly significant effect on the Caco-2 cells activity. ZnO NPs exerted higher cytotoxicity than Ag NPs in the same concentration range. ZnO NPs have dose-depended toxicity. The LD{sub 50} of ZnO NPs in Caco-2 cells is 0.431 mg/L. Significant depletion of SOD level, variation in GSH level and release of ROS in cells treated by ZnO NPs were observed, which suggests that cytotoxicity of ZnO NPs in intestine cells might be mediated through cellular oxidative stress. While Caco-2 cells treated with Ag NPs at all experimental concentrations showed no cellular oxidative damage. Moreover, the cells’ antioxidant capacity increased, and reached the highest level when the concentration of Ag NPs was 50 μg/mL. Therefore, it can be concluded that Ag NPs are safer antibacterial material in food packaging materials

  12. Genetics of Endometrial Cancers

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Okuda

    2010-01-01

    Full Text Available Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.

  13. Immunohistochemical Expression Of Estrogen And Progesterone Receptors In Endometrial Hyperplasia And Endometrioid Carcinoma

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    N Izadi-Mood

    2012-06-01

    Full Text Available Background: Endometrial carcinoma (EC is the most common gynecologic malignancy; however, mechanisms underlying its pathogenesis remain obscure.Endometrial carcinoma has been classified into two major categories: type I (related to estrogen or endometrioid adenocarcinomaand type II (unrelated to estrogen.Estrogen is the main trigger for the abnormal proliferation in the endometrial epithelium but progesterone can inhibit this process. The aim of this study was to analyze the expression of estrogen and progesterone receptors in all types of endometrial hyperplasia in comparison to endometrioid adenocarcinoma of endometrium. Methods: Forty-seven specimens including 23 cases of histopathologically confirmed hyperplastic endometrium (12 simple hyperplasia, 5 complex hyperplasia without atypia, and 6 complex hyperplasia with atypia and 24 cases of endometrial carcinoma were studied. Immunohistochemical staining of estrogen and progesterone receptors was performed in paraffin-embedded blocks and expression of estrogen and progesterone receptors were scored according to the proportion of positive staining cells. Results: Overexpression of progesterone receptors was seen in 18 (75% out of 24 cases of endometrial carcinoma and 23 (100% of all types of endometrial hyperplasia. The aforesaid differences were statistically significant (P=0.023. 70.8% of cases with endometrial carcinoma were 3+ for immunohistochemical staining of progesterone receptors as were 85.7% of the cases with endometrial hyperplasia; the difference being also statistically significant (P=0.02.Conclusion: Considering the increased proportion of progesterone receptor expression in all types of hyperplastic endometrium in comparison to endometrial carcinoma, hormonal therapy by progestinal agents is recommended as a treatment of choice.

  14. [Viral infection of herpes simplex, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, or adenovirus are not related to sinonasal adenocarcinomas].

    Science.gov (United States)

    Pérez Escuredo, Jhudit; Llorente, José Luis; Melón, Santiago; de Oña, María; García Martínez, Jorge; Alvarez Marcos, César; Hermsen, Mario

    2007-01-01

    Several types of virus have been implicated in the development of head and neck tumors. However, until now sinonasal adenocarcinomas (ACN) have not been studied. The aim of this study is to screen a series of ACN for the presence of a number of viruses known to play a role in cancer. Viral DNA sequences of herpes simplex virus, Epstein-Barr, varicela zoster, human papilloma, cytomegalovirus, and adenovirus were analysed by PCR in 37 primary ACN. Three tumors (8.1%) were positive for Epstein-Barr virus and 1 case (2.7%) for cytomegalovirus. Viral infections do not seem to play a role in the etiology of ACN.

  15. A new approach for pancreatic tissue engineering: human endometrial stem cells encapsulated in fibrin gel can differentiate to pancreatic islet beta-cell.

    Science.gov (United States)

    Niknamasl, Azadeh; Ostad, Seyed Nasser; Soleimani, Mansoureh; Azami, Mahmoud; Salmani, Maryam Kabir; Lotfibakhshaiesh, Nasrin; Ebrahimi-Barough, Somayeh; Karimi, Roya; Roozafzoon, Reza; Ai, Jafar

    2014-10-01

    Metabolic diabetes mellitus as the most serious and prevalent metabolic disease in the world has various complications. The most effective treatment of type I diabetes seems to be islet cell transplantation. Shortage of donors and difficult procedures and high rate of rejection have always restricted this approach. Tissue engineering is a novel effective solution to many medical problems such as diabetes. Endometrial mesenchymal stem cells as a lineage which have the potential to differentiate to mesodermal and endodermal tissues seem to be suitable for this purpose. Fibrin hydrogel with a high degree of biocompatibility and specific properties making it similar to normal pancreas seems to be an ideal scaffold. After successfully isolating stem cells (hEnSCs) from human endometrium, a three-step protocol was used to differentiate them into pancreatic beta cells. Fibrin was used as 3D scaffold. After 2 weeks, cells formed clusters like islets cells, and secretion of insulin was measured by chemiluminescence. PDX1, proinsulin, and c-peptide as special markers of β cells were detected by immunofluorescence. Expression of glucagon, PDX1, and insulin genes in mRNA level was detected by Real time PCR and gel electrophoresis. The former showed higher levels of gene expression in 3D cultures. SEM analysis showed good integrity between cells and scaffold. No toxicity was detected with fibrin scaffold by MTT assay.

  16. The Differentiation of Human Endometrial Stem Cells into Neuron-Like Cells on Electrospun PAN-Derived Carbon Nanofibers with Random and Aligned Topographies.

    Science.gov (United States)

    Mirzaei, Esmaeil; Ai, Jafar; Ebrahimi-Barough, Somayeh; Verdi, Javad; Ghanbari, Hossein; Faridi-Majidi, Reza

    2016-09-01

    Electrospun carbon nanofibers (CNFs) have great potential for applications in neural tissue regeneration due to their electrical conductivity, biocompatibility, and morphological similarity to natural extracellular matrix. In this study, we cultured human endometrial stem cells (hEnSCs) on electrospun CNFs with random and aligned topographies and demonstrated that hEnSCs could attach, proliferate, and differentiate into neural cells on both random and aligned CNFs. However, the proliferation, differentiation, and morphology of cells were affected by CNF morphology. Under the proliferative condition, hEnSCs showed lower proliferation on aligned CNFs than on random CNFs and on tissue culture plate (TCP) control. When cultured on aligned CNFs in neural induction media, hEnSCs showed significant upregulation of neuronal markers, NF-H and Tuj-1, and downregulation of neural progenitor marker (nestin) compared to that on random CNFs and on TCP. In contrast, hEnSCs showed higher expression of nestin and slight upregulation of oligodendrocyte marker (OLIG-2) on random CNFs compared to that on aligned CNFs and on TCP. SEM imaging revealed that differentiated cells extended along the CNF main axis on aligned CNFs but stretched multidirectionally on random CNFs. These findings suggest electrospun CNFs as proper substrate for stem cell differentiation into specific neural cells.

  17. Improved human endometrial stem cells differentiation into functional hepatocyte-like cells on a glycosaminoglycan/collagen-grafted polyethersulfone nanofibrous scaffold.

    Science.gov (United States)

    Khademi, Farzaneh; Ai, Jafar; Soleimani, Masoud; Verdi, Javad; Mohammad Tavangar, Seyed; Sadroddiny, Esmaeil; Massumi, Mohammad; Mahmoud Hashemi, Seyed

    2017-11-01

    Liver tissue engineering (TE) is rapidly emerging as an effective technique which combines engineering and biological processes to compensate for the shortage of damaged or destroyed liver tissues. We examined the viability, differentiation, and integration of hepatocyte-like cells on an electrospun polyethersulfone (PES) scaffold, derived from human endometrial stem cells (hEnSCs). Natural polymers were separately grafted on plasma-treated PES nanofibers, that is, collagen, heparan sulfate (HS) and collagen-HS. Galactosilated PES (PES-Gal) nanofibrous were created. The engineering and cell growth parameters were considered and compared with each sample. The cellular studies revealed increased cell survival, attachment, and normal morphology on the bioactive natural polymer-grafted scaffolds after 30 days of hepatic differentiation. The chemical and molecular assays displayed hepatocyte differentiation. These cells were also functional, showing glycogen storage, α-fetoprotein, and albumin secretion. The HS nanoparticle-grafted PES nanofibers demonstrated a high rate of cell proliferation, differentiation, and integration. Based on the observations mentioned above, engineered tissue is a good option in the future, for the commercial production of three-dimensional liver tissues for clinical purposes. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2516-2529, 2017. © 2016 Wiley Periodicals, Inc.

  18. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin

    Institute of Scientific and Technical Information of China (English)

    Yuan Guang Meng; Wei Dong Han; Ya Li Zhao; Ke Huang; Yi Ling Si; Zhi Qiang Wu; Yi Ming Mu

    2007-01-01

    LRP16 was previously identified as an estrogen-induced gene in breast cancer cells.The responsiveness of LRPl6to estrogen and its functional effects in endometrial cancer(EC)cells are still unclear.Here,we show that the mRNAlevel and promoter activity of the LRP16 gene were significantly increased by 17β-estradiol(E2)in estrogen receptorα(ERα)-positive Ishikawa human EC cells.Although the growth rate of Ishikawa cells was not obviously affected byectopic expression of LIP16,the results of a Transwell assay showed an approximate one-third increase of the invasivecapacity of LRP16-overexpressing cells.As a result of molecular screening,we observed that the expression of E-cadherin,an essential adhesion molecule associated with tumor metastasis,was repressed by LRP16.Further promoter analysesdemonstrated that LRP16 inhibited E-cadherin transactivation in a dose-dependent manner.However,the inhibition wasabolished by estrogen deprivation.indicating that the downregulation of E-cadherin transcription by LRP16 requiresERa mediation.Chromatin immunoprecipitation analyses revealed that the binding of ERa to the E-cadherin promoterwas antagonized by LRP16,suggesting that LRP16 could interfere with ERα-mediated transcription.These results sug-gest that the upregulation of LRP16 by estrogen could be involved in invasive growth by downregulating E-cadherin inhuman ECs.

  19. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

    Directory of Open Access Journals (Sweden)

    Mahboobeh eSafaeian

    2014-06-01

    Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

  20. Nanostructured delivery system for zinc phthalocyanine: preparation, characterization, and phototoxicity study against human lung adenocarcinoma A549 cells

    Directory of Open Access Journals (Sweden)

    Mariana da Volta Soares

    2011-01-01

    Full Text Available Mariana da Volta Soares1, Mainara Rangel Oliveira1, Elisabete Pereira dos Santos1, Lycia de Brito Gitirana2, Gleyce Moreno Barbosa3, Carla Holandino Quaresma3, Eduardo Ricci-Júnior11Department of Medicines, Laboratório de Desenvolvimento Galênico (LADEG, Faculty of Pharmacy, 2Laboratory of Animal and Comparative Histology, Glycobiology Research Program, Institute of Biomedical Science, 3Department of Medicines, Laboratório Multidisciplinar de Ciências Farmacêuticas, Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ, Rio de Janeiro, BrazilAbstract: In this study, zinc phthalocyanine (ZnPc was loaded onto poly-ε-caprolactone (PCL nanoparticles (NPs using a solvent emulsification–evaporation method. The process yield and encapsulation efficiency were 74.2% ± 1.2% and 67.1% ± 0.9%, respectively. The NPs had a mean diameter of 187.4 ± 2.1 nm, narrow distribution size with a polydispersity index of 0.096 ± 0.004, zeta potential of -4.85 ± 0.21 mV, and spherical shape. ZnPc has sustained release, following Higuchi’s kinetics. The photobiological activity of the ZnPc-loaded NPs was evaluated on human lung adenocarcinoma A549 cells. Cells were incubated with free ZnPc or ZnPc-loaded NPs for 4 h and then washed with phosphate-buffered saline. Culture medium was added to the wells containing the cells. Finally, the cells were exposed to red light (660 nm with a light dose of 100 J/cm2. The cellular viability was determined after 24 h of incubation. ZnPc-loaded NPs and free photosensitizer eliminated about 95.9% ± 1.8% and 28.7% ± 2.2% of A549 cells, respectively. The phototoxicity was time dependent up to 4 h and concentration dependent at 0–5 µg ZnPc. The cells viability decreased with the increase of the light dose in the range of 10–100 J/cm2. Intense lysis was observed in the cells incubated with the ZnPc-loaded NPs and irradiated with red light. ZnPc-loaded PCL NPs are the release systems that promise photodynamic

  1. Effects of fatty acids on benzo[a]pyrene uptake and metabolism in human lung adenocarcinoma A549 cells.

    Directory of Open Access Journals (Sweden)

    Rola Barhoumi

    Full Text Available Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action. In this investigation, the effects of control fatty acids (oleic acid (OA, linoleic acid (LA and n-3 PUFA, e.g., docosahexaenoic acid (DHA on the uptake and metabolism of the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP was investigated in A549 cells, a human adenocarcinoma alveolar basal epithelial cell line. A549 cells activate BaP through the cytochrome P450 enzyme system to form reactive metabolites, a few of which covalently bind to DNA and proteins. Therefore, multiphoton microscopy spectral analysis combined with linear unmixing was used to identify the parent compound and BaP metabolites formed in cells, in the presence and absence of fatty acids. The relative abundance of select metabolites was associated with altered P450 activity as determined using ethoxyresorufin-O-deethylase activity in cells cultured in the presence of BSA-conjugated fatty acids. In addition, the parent compound within cellular membranes increases significantly in the presence of each of the fatty acids, with the greatest accumulation observed following DHA treatment. DHA treated cells exhibit significantly lower pyrene-like metabolites indicative of lower adducts including DNA adducts compared to control BSA, OA or LA treated cells. Further, DHA reduced the abundance of the proximate carcinogen BaP 7,8-dihydrodiol and the 3-hydroxybenzo[a]pyrene metabolites compared to other treatments. The significant changes in BaP metabolites in DHA treated cells may be mediated by the effects on the physicochemical properties of the membrane known to affect enzyme activity related to phase I and phase II metabolism. In summary, DHA is a highly bioactive chemo

  2. GPER and ERα expression in abnormal endometrial proliferations.

    Science.gov (United States)

    Tica, Andrei Adrian; Tica, Oana Sorina; Georgescu, Claudia Valentina; Pirici, Daniel; Bogdan, Maria; Ciurea, Tudorel; Mogoantă, Stelian ŞtefăniŢă; Georgescu, Corneliu Cristian; Comănescu, Alexandru Cristian; Bălşeanu, Tudor Adrian; Ciurea, Raluca Niculina; Osiac, Eugen; Buga, Ana Maria; Ciurea, Marius Eugen

    2016-01-01

    G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERα. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERα, which was almost exclusively located in the nucleus. Both ERs' densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERα density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERα' density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER÷ERα ratio was significantly increased in high-grade lesions. The nuclear ERα is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERα expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERα's (and GPER's) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine÷protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER's presence is, at least partially, the result of an inductor effect of ERα on GPER gene transcription. In high-grade lesions, GPER÷ERα ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.

  3. Interphase cytogenetics of prostatic adenocarcinoma

    NARCIS (Netherlands)

    J.C. Alers (Janneke)

    1997-01-01

    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of

  4. Fat accumulation in adipose tissues as a risk factor for the development of endometrial cancer.

    Science.gov (United States)

    Nakamura, Keiichiro; Hongo, Atsushi; Kodama, Junichi; Hiramatsu, Yuji

    2011-07-01

    Fat accumulation in adipose tissues is a risk factor for the development of human cancers. However, there are no studies describing the fat accumulation in adipose tissue or its distribution in human endometrial cancer. We first examined fat accumulation in adipose tissues separately on CT images of 122 patients with endometrial cancer, and investigated the correlation of these findings with various histological types of endometrial cancers. Fat accumulation in adipose tissues [subcutaneous fat area (SFA) and/or visceral fat areas (VFA)] was strongly correlated with the group of obesity-related biological parameters (weight, body mass index (BMI), waist and body surface area (BSA)) in endometrial cancer. The incidence of type I endometrial cancer was more closely correlated with an increase in obesity-related parameters such as weight (p=0.011), BMI (p=0.006), waist circumference (p=0.038), BSA (p=0.016), SFA (p=0.005), total fat area (TFA) (p=0.006) and total cholesterol (T.Cho) (P=0.010) than type II endometrial cancer. In particular, the SFA was most strongly correlated with obesity-related biological parameters of type I endometrial cancer. The present findings indicate that type I endometrial cancer has a statistically significant increase in obesity-related biological parameters than type II endometrial cancer. We propose that the subcutaneous fat accumulation in adipose tissue is a strong risk factor for developing type I endometrial cancer.

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

    Science.gov (United States)

    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.

  6. miR-200 Regulates Endometrial Development During Early Pregnancy.

    Science.gov (United States)

    Jimenez, Patricia T; Mainigi, Monica A; Word, R Ann; Kraus, W Lee; Mendelson, Carole R

    2016-09-01

    For successful embryo implantation, endometrial stromal cells must undergo functional and morphological changes, referred to as decidualization. However, the molecular mechanisms that regulate implantation and decidualization are not well defined. Here we demonstrate that the estradiol- and progesterone-regulated microRNA (miR)-200 family was markedly down-regulated in mouse endometrial stromal cells prior to implantation, whereas zinc finger E-box binding homeobox-1 and -2 and other known and predicted targets were up-regulated. Conversely, miR-200 was up-regulated during in vitro decidualization of human endometrial stromal cells. Knockdown of miR-200 negatively affected decidualization and prevented the mesenchymal-epithelial transition-like changes that accompanied decidual differentiation. Notably, superovulation of mice and humans altered miR-200 expression. Our findings suggest that hormonal alterations that accompany superovulation may negatively impact endometrial development and decidualization by causing aberrant miR-200 expression.

  7. Two-way communication between endometrial stromal cells and monocytes.

    Science.gov (United States)

    Klinkova, Olga; Hansen, Keith A; Winterton, Emily; Mark, Connie J; Eyster, Kathleen M

    2010-02-01

    Immune system cells and cells of the endometrium have long been proposed to interact in both physiological and pathological processes. The current study was undertaken to examine communication between cultured monocytes and endometrial stromal cells and also to assess responses of endometrial stromal cells for treatment with estradiol (E) in the absence and presence of medroxyprogesterone acetate (P). A telomerase-immortalized human endometrial stromal cell (T-HESC) line and the U937 monocyte cell line were used. Telomerase-immortalized human endometrial stromal cells were treated with E +/- P +/- monocyte conditioned medium; U937 were treated +/- T-HESC conditioned medium. Gene expression in response to treatment was examined by DNA microarray. Bidirectional communication, as demonstrated by changes in gene expression, clearly occurred between U937 monocytes and T-HESC.

  8. 三氧化二砷对人子宫内膜癌移植瘤的影响%EFFECTS OF ARSENIC TRIOXIDE ON HUMAN ENDOMETRIAL CANCER XENOGRAFT

    Institute of Scientific and Technical Information of China (English)

    胡美丽; 李利; 王晓玲; 康山

    2014-01-01

    目的:探讨三氧化二砷(aresenic trioxide,AS2 O3)对裸鼠荷人子宫内膜癌皮下移植瘤的生长抑制作用及作用机制。方法建立裸鼠荷人子宫内膜癌 HEC-1-A 细胞移植瘤动物模型,随机分为5组,A 组(AS2 O34mg· kg-1·d-1)、B 组(AS2 O36mg·kg-1·d-1)、C 组(AS2 O38mg·kg-1·d-1)、D 组(顺铂3mg·kg-1·d-1)、阴性对照 E 组(生理盐水组),腹腔连续给药14d,计算瘤体积和瘤质量抑制率,观察用药前后裸鼠体质量改变。结果A、B、C、D 组肿瘤体积抑制率分别为50.97%、75.58%、56.92%、52.23%,肿瘤质量抑制率分别为10.15%、29.33%、16.67%、14.69%,与 E 组比较差异均有统计学意义(P <0.05)。用药前后 AS2 O3各组体质量变化不明显,而 D 组裸鼠体质量变化差异有统计学意义。结论 AS2 O3对鼠荷人子宫内膜癌移植瘤的生长有抑制作用,且治疗剂量的AS2 O3对子宫内膜癌异种移植瘤的抑制作用强于顺铂,而不良反应弱,因此 AS2 O3有希望成为一种新型的子宫内膜癌治疗药物。%Objective To explore the inhibitory effect of arsenic troixide(AS2 O 3 )on the growth of nude mice bearing human endometrial carcinoma transplanted subcutaneously and its mechanisms.Methods Human endometrial cancer xenograft models were established in nude mice using HEC-1-A cell,then were divided into five groups as following,group A(AS2 O 3 4mg· kg-1 ·d-1 ),group B(AS2 O3 6mg· kg-1 · d-1 ),group C(AS2 O 3 8mg· kg-1 · d-1 ),group D (cisplatin 3mg·kg-1 ·d-1 ),and group E(saline group).The drugs were given intraperitoneally for 14 d,then the inhibition rate of tumor volume and tumor mass were calculated.The change of body mass of nude mice after treatment was measured.Results The tumor volume was inhibited by 50.97%,75.58%,56.92%,52.23%,and the tumor mass was inhibited by 10.15%,29.33%, 16.67%,14.69%,respectively,in group A,group B

  9. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

    Directory of Open Access Journals (Sweden)

    Kaoru Miyazaki

    Full Text Available BACKGROUND: Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay. METHODOLOGY/PRINCIPAL FINDINGS: ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells. CONCLUSIONS/SIGNIFICANCE: We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo

  10. MCF-7 human mammary adenocarcinoma cells exhibit augmented responses to human insulin on a collagen IV surface

    DEFF Research Database (Denmark)

    Listov-Saabye, Nicolai; Jensen, Marianne Blirup; Kiehr, Benedicte;

    2009-01-01

    was significantly more mitogenic than native insulin, validating the ability of the assay to identify hypermitogenic human insulin analogs. With MCF-7 cells on a collagen IV surface, the ranking of mitogens was maintained, but fold mitogenic responses and dynamic range and steepness of dose-response curves were...

  11. LeftyA sensitive cytosolic pH regulation and glycolytic flux in Ishikawa human endometrial cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Salker, Madhuri S.; Zhou, Yuetao; Singh, Yogesh [Department of Physiology, University of Tuebingen, 72076 Tuebingen (Germany); Brosens, Jan [Division of Reproductive Health, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospital, Coventry CV2 2DX (United Kingdom); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tuebingen, 72076 Tuebingen (Germany)

    2015-05-08

    Objective: LeftyA, a powerful regulator of stemness, embryonic differentiation, and reprogramming of cancer cells, counteracts cell proliferation and tumor growth. Key properties of tumor cells include enhanced glycolytic flux, which is highly sensitive to cytosolic pH and thus requires export of H{sup +} and lactate. H{sup +} extrusion is in part accomplished by Na{sup +}/H{sup +} exchangers, such as NHE1. An effect of LeftyA on transport processes has, however, never been reported. The present study thus explored whether LeftyA modifies regulation of cytosolic pH (pHi) in Ishikawa cells, a well differentiated endometrial carcinoma cell model. Methods: NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance quantified by Western blotting, pH{sub i} estimated utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na{sup +}/H{sup +} exchanger activity from Na{sup +} dependent realkalinization after an ammonium pulse, and lactate concentration in the supernatant utilizing an enzymatic assay and subsequent colorimetry. Results: A 2 h treatment with LeftyA (8 ng/ml) significantly decreased NHE1 transcript levels (by 99.6%), NHE1 protein abundance (by 71%), Na{sup +}/H{sup +} exchanger activity (by 55%), pHi (from 7.22 ± 0.02 to 7.05 ± 0.02), and lactate release (by 41%). Conclusions: LeftyA markedly down-regulates NHE1 expression, Na{sup +}/H{sup +} exchanger activity, pHi, and lactate release in Ishikawa cells. Those effects presumably contribute to cellular reprogramming and growth inhibition. - Highlights: • LeftyA, an inhibitor of tumor growth, reduces Na{sup +}/H{sup +}-exchanger activity by 55%. • LeftyA decreases NHE1 transcripts by 99.6% and NHE1 protein by 71%. • LeftyA decreases cytosolic pH from 7.22 ± 0.02 to 7.05 ± 0.02. • Cytosolic acidification by Lefty A decreases glycolysis by 41%. • Cytosolic acidification by Lefty A compromises energy production of tumor cells.

  12. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  13. Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies

    DEFF Research Database (Denmark)

    Ljubimov, A V; Bartek, J; Couchman, J R

    1992-01-01

    -membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated......-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases....

  14. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian, E-mail: zhangjian197011@yahoo.com [Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China); Zhang, Tao [Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Ti, Xinyu; Shi, Jieran; Wu, Changgui; Ren, Xinling [Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China); Yin, Hong, E-mail: yinnhong@yahoo.com [The Medical Image Center, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China)

    2010-08-13

    Research highlights: {yields} Curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells {yields} Curcumin promotes apoptosis in A549/DDP cells through a miRNA signaling pathway {yields} Curcumin induces A549/DDP cell apoptosis by downregulating miR-186* {yields} miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin -- Abstract: Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186* in A549/DDP. In addition, transfection of cells with a miR-186* inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186* significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.

  15. Quantification of intracellular phosphorylated carbohydrates in HT29 human colon adenocarcinoma cell line using liquid chromatography-electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Vizán, Pedro; Alcarraz-Vizán, Gema; Díaz-Moralli, Santiago; Rodríguez-Prados, Juan Carlos; Zanuy, Míriam; Centelles, Josep J; Jáuregui, Olga; Cascante, Marta

    2007-07-01

    The quantitative understanding of the role of sugar phosphates in regulating tumor energetic metabolism at the proteomic and genomic level is a prerequisite for an efficient rational design in combined drug chemotherapy. Therefore, it is necessary to determine accurately the concentration of the main sugar phosphate pools at the lower concentrations present in the often-limited volume of tumor cell samples. Taking as an example the human adenocarcinoma cell line HT29, we here report a fast and reliable quantitative method based on the use of liquid nitrogen, a weak acid extraction, and liquid chromatography-electrospray ionization tandem mass spectrometry to quantify simultaneously the intracellular concentration of sugar phosphate pools. The method was set up using standard addition curves. Thus, it is possible to identify and quantify hexose phosphate, pentose phosphate, and triose phosphate pools up to 0.02-0.10 ng x microL(-1), depending on the analyte. The method developed was here used for the quantitative study of changes in phosphorylated carbohydrates of central carbon metabolism when high or low glucose concentration conditions are induced in vitro in the HT29 human colon adenocarcinoma cell line.

  16. Enhancing neuronal growth from human endometrial stem cells derived neuron-like cells in three-dimensional fibrin gel for nerve tissue engineering.

    Science.gov (United States)

    Navaei-Nigjeh, Mona; Amoabedini, Ghasem; Noroozi, Abbas; Azami, Mahmoud; Asmani, Mohammad N; Ebrahimi-Barough, Somayeh; Saberi, Hooshang; Ai, Armin; Ai, Jafar

    2014-08-01

    Nerve tissue engineering (NTE) is one of the most promising methods to restore central nerve systems in human health care. Three-dimensional (3D) distribution and growth of cells within the porous scaffold composed of nanofibers are of clinical significance for NTE. In this study, an attempt was made to develop and characterize the use of fibrin gel and human endometrial stem cells (hEnSCs)-derived neuron-like cells simultaneously to support cell behavior especially neuron outgrowth. The structural and mechanical characteristics of fibrin gel scaffold were examined with SEM and rheometer. Also, hEnSCs-derived neuron-like cells were cultured in fibrin gel and were subsequently analyzed with immunofluorescent staining against neuronal markers. In parallel, the survival and growth rates of the cells were determined by MTT assay and neurite extension. At the end, cell-matrix interactions were investigated with SEM and TEM micrographs. Mechanical properties of fabricated scaffold were studied and results indicated appropriate choice of material, SEM and TEM showed excellent integration of cells with nanofibers regarding the relation between cells and fibrin gel. Immunofluorescent staining of fibrin gel after 6 days of cell seeding and culture demonstrated well expanded and incorporated network of neurons. In addition, viability, proliferation, and neuronal growth of seeded cells were analyzed at days 1, 3, and 6. Comparing those results with 2D culture of seeded cells showed positive effect of 3D culture. Taken together, the results suggest that fibrin can provide a suitable, three-dimensional scaffold for neuronal survival and outgrowth for regeneration of the central nervous system. © 2013 Wiley Periodicals, Inc.

  17. The Discussion of Establishing Human Endometrial Carcinoma Xenografts in Ovariectomized Nude Mice%建立去势雌性裸小鼠人子宫内膜癌皮下移植瘤动物模型的探讨

    Institute of Scientific and Technical Information of China (English)

    李玲; 廖秦平

    2012-01-01

    Objective:To discuss the influence of total irradiation on the human endometrial carcinoma xenografts in the ovariectomized nude mice. Methods:One week after the ovariectomy,the female nude mice were randomly distributed into two groups:non-irradiated group and irradiated group. Trie endometrial cells,which had been cultured in vitro,was subcutaneously transplanted into the nude mice one week after the surgery, in the irradiated group the mice were exposed to 4 Gy of total body irradiation 3 h pior to injection with endometrial cells,in the non-irradiated group the mice were injected with endometrial cells in the same time.the mice weight,survival rate and tumor growth of both groups were observed,the diameters of tumors was measured and the volume of tumors was calculated. Results:The both groups have 100% tumor growth; the difference in tumor sizes is not significant (P<0.05). Conclusions:Total body irradiation did not affect the tumor-take rate on human endometrial carcinoma xenografts in ovariectomized nude mice, but increased the death rate of nude mices.%目的:探讨全身外照射对建立切除卵巢后雌性裸小鼠子宫内膜癌皮下移植瘤模型成瘤率的影响.方法:将切除卵巢后1周的裸小鼠随机分为两组,一组全身外照射(4 Gy)3 h后皮下注射子宫内膜癌细胞悬液,另一组未予照射同时间皮下注射子宫内膜癌细胞悬液,观察裸小鼠体质量变化、存活情况和肿瘤的生长情况,测量肿瘤径线并计算体积.结果:2组成瘤率100%;各组肿瘤体积差异无统计学意义(P>0.05),但存活率差异有统计学意义(P<0.05).结论:全身外照射不影响切除卵巢的裸小鼠的成瘤率,但增加裸小鼠的死亡率.

  18. Differentiating rectal carcinoma by an immunohistological analysis of carcinomas of pelvic organs based on the NCBI Literature Survey and the Human Protein Atlas database.

    Science.gov (United States)

    Miura, Koh; Ishida, Kazuyuki; Fujibuchi, Wataru; Ito, Akihiro; Niikura, Hitoshi; Ogawa, Hitoshi; Sasaki, Iwao

    2012-06-01

    The treatments and prognoses of pelvic organ carcinomas differ, depending on whether the primary tumor originated in the rectum, urinary bladder, prostate, ovary, or uterus; therefore, it is essential to diagnose pathologically the primary origin and stages of these tumors. To establish the panels of immunohistochemical markers for differential diagnosis, we reviewed 91 of the NCBI articles on these topics and found that the results correlated closely with those of the public protein database, the Human Protein Atlas. The results revealed the panels of immunohistochemical markers for the differential diagnosis of rectal adenocarcinoma, in which [+] designates positivity in rectal adenocarcinoma and [-] designates negativity in rectal adenocarcinoma: from bladder adenocarcinoma, CDX2[+], VIL1[+], KRT7[-], THBD[-] and UPK3A[-]; from prostate adenocarcinoma, CDX2[+], VIL1[+], CEACAM5[+], KLK3(PSA)[-], ACPP(PAP)[-] and SLC45A3(prostein)[-]; and from ovarian mucinous adenocarcinoma, CEACAM5[+], VIL1[+], CDX2[+], KRT7[-] and MUC5AC[-]. The panels of markers distinguishing ovarian serous adenocarcinoma, cervical carcinoma, and endometrial adenocarcinoma were also represented. Such a comprehensive review on the differential diagnosis of carcinomas of pelvic organs has not been reported before. Thus, much information has been accumulated in public databases to provide an invaluable resource for clinicians and researchers.

  19. Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

    Science.gov (United States)

    Mounier, C M; Wendum, D; Greenspan, E; Fléjou, J-F; Rosenberg, D W; Lambeau, G

    2008-01-01

    Recent studies suggest that secreted phospholipases A2 (sPLA2s) represent attractive potential tumour biomarkers and therapeutic targets for various cancers. As a first step to address this issue in human colorectal cancer, we examined the expression of the full set of sPLA2s in sporadic adenocarcinomas and normal matched mucosa from 21 patients by quantitative PCR and immunohistochemistry. In normal colon, PLA2G2A and PLA2G12A were expressed at high levels, PLA2G2D, PLA2G5, PLA2G10 and PLA2G12B at moderate levels, and PLA2G1B, PLA2G2F and PLA2G3 at low levels. In adenocarcinomas from left and right colon, the expression of PLA2G3 was increased by up to 40-fold, while that of PLA2G2D and PLA2G5 was decreased by up to 23- and 14-fold. The variations of expression for sPLA2-IID, sPLA2-III and sPLA2-V were confirmed at the protein level. The expression pattern of these sPLA2s appeared to be linked respectively to the overexpression of interleukin-8, defensin α6, survivin and matrilysin, and downregulation of SFRP-1 and RLPA-1, all these genes being associated to colon cancer. This original sPLA2 profile observed in adenocarcinomas highlights the potential role of certain sPLA2s in colon cancer and suggests that sPLA2-III might be a good candidate as a novel biomarker for both left and right colon cancers. PMID:18212756

  20. Endometrium adenocarcinoma: last five years retrospective case at Hospital do Servidor Publico from Sao Paulo State, SP, Brazil; Adenocarcinoma do endometrio: retrospectiva de casos dos ultimos cinco anos no Hospital do Servidor Publico Estadual Francisco Morato de Oliveira, Sao Paulo

    Energy Technology Data Exchange (ETDEWEB)

    Millen, Eduardo Camargo; Blesa, Ana Cristina Poli; Silva, Fabiana Ruas Domingues da; Lopes, Luis Augusto Freire; Baracat, Fausto F.; Lopes, Reginaldo Guedes Coelho; Lippi, Umberto Gazzi [Hospital do Servidor Publico Estadual Francisco Morato de Oliveira, Sao Paulo, SP (Brazil)

    2003-07-01

    The present study is an institutional review of endometrial adenocarcinoma in patients of a public hospital for state civil servants in the city of Sao Paulo, the Francisco Morato de Oliveira Civil Servants Hospital, from January 1996 to October 2000. The following factors were considered: age of disease onset, age of menarche and menopause, number of pregnancies, use of hormone-replacement therapy, and associated morbidities such as diabetes mellitus, obesity and hypertension. The conclusion was that a history of menstrual disorders and vaginal bleeding in post-menopausal period, such as hypermenorraghia and endometrial thickness greater than four millimeters in post menopausal women, must be accurately investigated for endometrial neoplasia. (author)

  1. Treatment Options by Stage (Endometrial Cancer)

    Science.gov (United States)

    ... of endometrial cancer. Signs and symptoms of endometrial cancer include unusual vaginal bleeding or pain in the pelvis. These and other signs and symptoms may be caused by endometrial cancer or by other conditions. Check with your doctor ...

  2. Endometrial Stromal Hyperplasia: An Underrecognized Condition

    OpenAIRE

    Efthimios Sivridis; Gerasimos Koutsougeras; Alexandra Giatromanolaki

    2013-01-01

    Hyperplasia of the endometrial stroma is a poorly recognized lesion, lacking widespread recognition with most, if not all, such cases sequestrated in the literature as endometrial stromal nodules or low-grade endometrial stromal sarcomas. In this paper, we describe three examples of “endometrial stromal hyperplasia” which have a remarkable morphological similarity with the normally proliferating endometrial stroma and the endometrial stromal neoplasms, but which also possess subtle, but suffi...

  3. Polycystic ovary syndrome and risk of endometrial cancer: a mini-review.

    Science.gov (United States)

    Tokmak, Aytekin; Kokanali, Mahmut Kuntay; Guzel, Ali Irfan; Kara, Aydan; Topcu, Hasan Onur; Cavkaytar, Sabri

    2014-01-01

    The polycystic ovary syndrome is the most common endocrinological disorder of reproductive age women with a prevalence of 5 to 8 %. The most common diagnostic criteria used for polycystic ovary syndrome are oligo- or an-ovulation, clinical and/ or biochemical signs of hyperandrogenism and polycystic ovaries. Hyperandrogenism results in increased estrogen levels and lack of cyclic progesterone due to anovulation and persistent stimulation of the endometrium may lead to endometrial hyperplasia or adenocarcinoma development. In this mini review, we aimed to evaluate the possible relationship between polycystic ovary syndrome and endometrial cancer.

  4. Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice.

    Science.gov (United States)

    Tang, Qi-Ling; Guo, Ji-Quan; Wang, Qi-You; Lin, Hai-Shu; Yang, Zhou-Ping; Peng, Tong; Pan, Xue-Diao; Liu, Bing; Wang, Su-Jun; Zang, Lin-Quan

    2015-01-01

    Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

  5. Serum tetranectin and CA125 in endometrial adenocarcinoma

    DEFF Research Database (Denmark)

    Lundstrøm, M S; Høgdall, C K; Nielsen, Anette Lynge;

    2000-01-01

    in relation to tumor grade, stage and cancer survival. RESULTS: The CA125 levels correlated significantly with tumor stage. Dichotomized according to a cut-off level of 35 U/ml, CA125 significantly correlated with cancer death. Multivariate regression analysis of cancer survival time showed that CA125 > 35 U/ml...

  6. Direct sampling of metastatic ovarian carcinoma masquerading as endocervical adenocarcinoma in liquid-based cytology cervical sample

    Science.gov (United States)

    Gupta, Nalini; Bhar, Vikrant; Dey, Pranab; Rajwanshi, Arvind; Suri, Vanita

    2014-01-01

    Cervical sample is routinely taken to identify squamous dysplastic lesions of the cervix. Glandular lesions are far less commonly reported on cervical samples. The most common glandular lesion reported on cervical smear is endocervical adenocarcinoma, followed by endometrial adenocarcinoma. Direct sampling by Cervex brush is possible even in endometrial adenocarcinoma, if the tumor directly involves lower uterine segment/endocervical canal. Metastases to cervix are rare but have occasionally been reported in previous reports. We wish to highlight in this case, metastatic ovarian carcinoma directly sampled in cervical liquid-based cytology (LBC) sample, which mimicked cytomorphologically a well-differentiated endocervical adenocarcinoma. To the best of our knowledge, a similar case has not been previously published in SurePath LBC sample. PMID:25538388

  7. miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting MET.

    Science.gov (United States)

    Chen, Qing-Yong; Jiao, De-Min; Wang, Jian; Hu, Huizhen; Tang, Xiali; Chen, Jun; Mou, Hao; Lu, Wei

    2016-04-26

    MicroRNAs (miRNAs) play a critical role in drug resistance and epithelial-mesenchymal transition (EMT). The aims of this study were to explore the potential role of miR-206 in governing cisplatin resistance and EMT in lung cancer cells. We found that both lung adenocarcinoma A549 cisplatin-resistant cells (A549/DDP) and H1299 cisplatin-resistant cells (H1299/DDP) acquired mesenchymal features and were along with low expression of miR-206 and high migration and invasion abilities. Ectopic expression of miR-206 mimics inhibited cisplatin resistance, reversed the EMT phenotype, decreased the migration and invasion in these DDP-resistant cells. In contrast, miR-206 inhibitors increased cisplatin resistance, EMT, cell migration and invasion in non-DDP-resistant cells. Furthermore, we found that MET is the direct target of miR-206 in lung cancer cells. Knockdown of MET exhibited an EMT and DDP resistant inhibitory effect on DDP-resistant cells. Conversely, overexpression of MET in non-DDP- resistant cells produced a promoting effect on cell EMT and DDP resistance. In lung adenocarcinoma tissues, we demonstrated that low expression of miR-206 were also correlated with increased cisplatin resistance and MET expression. In addition, we revealed that miR-206 overexpression reduced cisplatin resistance and EMT in DDP-resistant cells, partly due to inactivation of MET/PI3K/AKT/mTOR signaling pathway, and subsequent downregulation of MDR1, ZEB1 and Snail expression. Finally, we found that miR-206 could also sensitize A549/DDP cells to cisplatin in mice model. Taken together, our study implied that activation of miR-206 or inactivation of its target gene pathway could serve as a novel approach to reverse cisplatin resistance in lung adenocarcinomas cells.

  8. Generation of human endometrial knockout cell lines with the CRISPR/Cas9 system confirms the prostaglandin F2α synthase activity of aldo-ketoreductase 1B1.

    Science.gov (United States)

    Lacroix Pépin, Nicolas; Chapdelaine, Pierre; Rodriguez, Yoima; Tremblay, Jacques-P; Fortier, Michel A

    2014-07-01

    Prostaglandins (PGs) are important regulators of female reproductive function. The primary PGs produced in the endometrium are PGE2 and PGF2α. Relatively little is known about the biosynthetic pathways leading to the formation of PGF2α. We have described the role of aldo-ketoreductase (AKR)1B1 in increased PGF2α production by human endometrial cells following stimulation with interleukin-1β (IL-1β). However, alternate PGF synthases are expressed concurrently in endometrial cells. A definite proof of the role of AKR1B1 would require gene knockout; unfortunately, this gene has no direct equivalent in the mouse. Recently, an efficient genome-editing technology using RNA-guided DNase Cas9 and the clustered regularly interspaced short palindromic repeats (CRISPR) system has been developed. We have adapted this approach to knockout AKR1B1 gene expression in human endometrial cell lines. One clone (16-2) of stromal origin generated by the CRISPR/Cas9 system exhibited a complete loss of AKR1B1 protein and mRNA expression, whereas other clones presented with partial edition. The present report focuses on the characterization of clone 16-2 exhibiting deletion of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this clone lost their ability to produce PGF2α but maintained their original stromal cell (human endometrial stromal cells-2) phenotype including the capacity to decidualize in the presence of progesterone (medroxyprogesterone acetate) and 8-bromo-cAMP. Knockout cells also maintained their ability to increase PGE2 production in response to IL-1β. In summary, we demonstrate that the new genome editing CRISPR/Cas9 system can be used in human cells to generate stable knockout cell line models. Our results suggest that genome editing of human cell lines can be used to complement mouse KO models to validate the function of genes in differentiated tissues and cells. Our results also confirm that AKR1B1 is involved in the synthesis of PGF2α.

  9. 人肺腺癌多西他赛耐药机制的研究%Research on the mechanisms of docetaxel-resistant human lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    陈龙邦

    2012-01-01

    深入研究肺腺癌对多西他赛(docetaxel,DTX)耐药的分子机制,不仅有助于筛选出可用于临床指导DTX个体化用药的分子靶标,也可为耐药的干预策略研究提供研究方向.笔者课题组采用体外逐步提高DTX浓度的方法诱导建立了稳定传代的人肺腺癌SPC-A1耐DTX细胞系SPC-A1/DTX,并从细胞形态、化疗敏感性、增殖、凋亡、细胞周期、药物转运等方面比较了亲本细胞与耐药细胞间的差异.进一步通过基因芯片及miRNA芯片分析,筛选出耐药细胞中差异表达显著的基因(如ING4)以及miRNA(如miR-200b、miR-100),在体内、外模型中进行功能获得性和(或)缺失性研究,证实ING4表达下调、miR-200b/E2F3及miR-100/Plk-1通路的异常参与了肺腺癌细胞DTX耐药表型的形成.%In-depth study of the molecular mechanisms of lung adenocarcinoma resistance to docetaxel ( DTX ) not only offers us the new promising targets of individualized treatment for lung adenocarcinoma patients, but also provides new insights into clinical intervention strategies. In this study, the docetaxel-resistant human lung adenocarcinoma cell line SPC-Al/DTX was derived from parental SPC-A1 cell line by continuous exposure to increasing concentration of DTX in vitro. Differences in biological characteristics, such as cell morphology, chemosensitivity, cell proliferation, apoptosis, cell cycle, and drug transportation were compared between SPC-A1 and SPC-A1/DTX cell lines. Based on gene expression-and miRNA-microarray analysis, differentially expressed genes, such as ING4 and miRNAs ( e. G. miR-200b and miR-100) were screened out from SPC-A1/DTX cells. With further gain-of-function and (or) loss-of-function studies of these molecules in both in vitro and in vivo models, we provided potential mechanistic explanations for DTX resistance of human lung adenocarcinoma. It was found that down-regulation of ING4 gene and abnormalities of crosstalk between miR-200b and E2F3 gene

  10. Apoptotic activity of genistein on human lung adenocarcinoma SPC-A-1 cells and preliminary exploration of its mechanisms using microarray.

    Science.gov (United States)

    Zou, Huafei; Zhan, Shuxuan; Cao, Kaiming

    2008-11-01

    Soy isoflavone genistein is active against certain solid malignancies, but its direct effect on lung adenocarcinoma and its mechanisms of action remain to be elucidated. In the present study, using the human lung adenocarcinoma cell line SPC-A-1, we found that genistein decreased SPC-A-1 cell viability in both a dose and time dependent manner. Flow cytometry analysis revealed that genistein significantly induced arrest of SPC-A-1 cells at the G2/M phase of the cell cycle. Furthermore, through DNA fragmentation and TUNEL assays, we demonstrated that the addition of genistein led to SPC-A-1 apoptosis in both a dose and time dependent manner. Finally, the apoptosis pathway-related gene expression profile affected by genistein was investigated using the oligonucleotide microarray method. The result showed that the expression profile of 20 genes (ratio of genistein group/control group >2 or <0.5) related to the apoptotic pathways changed. These genes, mainly consisting of the Bcl-2 family and TNF ligand and receptor family, are involved in regulation of the apoptosis process.

  11. MiR-100 resensitizes docetaxel-resistant human lung adenocarcinoma cells (SPC-A1) to docetaxel by targeting Plk1.

    Science.gov (United States)

    Feng, Bing; Wang, Rui; Chen, Long-Bang

    2012-04-28

    MicroRNAs (miRNAs) expression correlates with biological characteristics of both normal cells and cancer cells, but their roles in cancer chemoresistance remain unclear. By microarray analysis, miR-100 was found significantly down-regulated in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-100 expression resensitized SPC-A1/DTX cells to docetaxel by suppression of cell proliferation and induction of cell arrest in G(2)/M phase and apoptosis. Knock-down of Plk1, which was a direct target of miR-100, yielded similar effects as that of ectopic miR-100 expression. The inverse correlation between miR-100 and Plk1 expression was also detected in nude mice SPC-A1/DTX tumor xenografts and clinical lung adenocarcinoma tissues and was proved to be related with the in vivo response to docetaxel. Thus, our results suggested that down-regulation of miR-100 could lead to Plk1 over-expression and eventually to docetaxel chemoresistance of human lung adenocarcinoma. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. 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

  13. Inhibition of AHR transcription by NF1C is affected by a single-nucleotide polymorphism, and is involved in suppression of human uterine endometrial cancer.

    Science.gov (United States)

    Li, D; Takao, T; Tsunematsu, R; Morokuma, S; Fukushima, K; Kobayashi, H; Saito, T; Furue, M; Wake, N; Asanoma, K

    2013-10-10

    Involvement of the aryl hydrocarbon receptor (AHR) in carcinogenesis has been suggested in many studies. Upregulation of AHR has been reported in some cancer species, and an association between single-nucleotide polymorphisms (SNPs) of AHR and cancer risk or cancer development has also been reported. This evidence suggests the involvement of some specific SNPs in AHR transcriptional regulation in the process of carcinogenesis or cancer development, but there have been no studies to elucidate the mechanism involved. In this study, we identified the transcription factor Nuclear Factor 1-C (NF1C) as a candidate to regulate AHR transcription in a polymorphism-dependent manner. SNP rs10249788 was included in a consensus binding site for NF1C. Our results suggested that NF1C preferred the C allele to the T allele at rs10249788 for binding. Forced expression of NF1C suppressed the activity of the AHR promoter with C at rs10249788 stronger than that with T. Moreover, expression analysis of human uterine endometrial cancer (HEC) specimens showed greater upregulation of AHR and downregulation of NF1C than those of normal endometrium specimens. Sequence analysis showed HEC patients at advanced stages tended to possess T/T alleles more frequently than healthy women. We also demonstrated that NF1C suppressed proliferation, motility and invasion of HEC cells. This function was at least partially mediated by AHR. This study is the first to report that a polymorphism on the AHR regulatory region affected transcriptional regulation of the AHR gene in vitro. Because NF1C is a tumor suppressor, our new insights into AHR deregulation and its polymorphisms could reveal novel mechanisms of genetic susceptibility to cancer.

  14. Arecoline induced disruption of expression and localization of the tight junctional protein ZO-1 is dependent on the HER 2 expression in human endometrial Ishikawa cells.

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    Giri, Sarbani; Poindexter, Kevin M; Sundar, Shyam N; Firestone, Gary L

    2010-07-06

    Approximately 600 million people chew Betel nut, making this practice the fourth most popular oral habit in the world. Arecoline, the major alkaloid present in betel nut is one of the causative agents for precancerous lesions and several cancers of mouth among those who chew betel nut. Arecoline can be detected in the human embryonic tissue and is correlated to low birth weight of newborns whose mothers chew betel nut during pregnancy, suggesting that arecoline can induce many systemic effects. However, few reports exist as to the effects of arecoline in human tissues other than oral cancer cell lines. Furthermore, in any system, virtually nothing is known about the cellular effects of arecoline treatment on membrane associated signaling components of human cancer cells. Using the human Ishikawa endometrial cancer cell line, we investigated the effects of arecoline on expression, localization and functional connections between the ZO-1 tight junction protein and the HER2 EGF receptor family member. Treatment of Ishikawa cells with arecoline coordinately down-regulated expression of both ZO-1 and HER2 protein and transcripts in a dose dependent manner. Biochemical fractionation of cells as well as indirect immunofluorescence revealed that arecoline disrupted the localization of ZO-1 to the junctional complex at the cell periphery. Compared to control transfected cells, ectopic expression of exogenous HER2 prevented the arecoline mediated down-regulation of ZO-1 expression and restored the localization of ZO-1 to the cell periphery. Furthermore, treatment with dexamethasone, a synthetic glucocorticoid reported to up-regulate expression of HER2 in Ishikawa cells, precluded arecoline from down-regulating ZO-1 expression and disrupting ZO-1 localization. Arecoline is known to induce precancerous lesions and cancer in the oral cavity of betel nut users. The arecoline down-regulation of ZO-1 expression and subcellular distribution suggests that arecoline potentially

  15. Arecoline induced disruption of expression and localization of the tight junctional protein ZO-1 is dependent on the HER 2 expression in human endometrial Ishikawa cells

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    Sundar Shyam N

    2010-07-01

    Full Text Available Abstract Background Approximately 600 million people chew Betel nut, making this practice the fourth most popular oral habit in the world. Arecoline, the major alkaloid present in betel nut is one of the causative agents for precancerous lesions and several cancers of mouth among those who chew betel nut. Arecoline can be detected in the human embryonic tissue and is correlated to low birth weight of newborns whose mothers chew betel nut during pregnancy, suggesting that arecoline can induce many systemic effects. However, few reports exist as to the effects of arecoline in human tissues other than oral cancer cell lines. Furthermore, in any system, virtually nothing is known about the cellular effects of arecoline treatment on membrane associated signaling components of human cancer cells. Results Using the human Ishikawa endometrial cancer cell line, we investigated the effects of arecoline on expression, localization and functional connections between the ZO-1 tight junction protein and the HER2 EGF receptor family member. Treatment of Ishikawa cells with arecoline coordinately down-regulated expression of both ZO-1 and HER2 protein and transcripts in a dose dependent manner. Biochemical fractionation of cells as well as indirect immunofluorescence revealed that arecoline disrupted the localization of ZO-1 to the junctional complex at the cell periphery. Compared to control transfected cells, ectopic expression of exogenous HER2 prevented the arecoline mediated down-regulation of ZO-1 expression and restored the localization of ZO-1 to the cell periphery. Furthermore, treatment with dexamethasone, a synthetic glucocorticoid reported to up-regulate expression of HER2 in Ishikawa cells, precluded arecoline from down-regulating ZO-1 expression and disrupting ZO-1 localization. Conclusion Arecoline is known to induce precancerous lesions and cancer in the oral cavity of betel nut users. The arecoline down-regulation of ZO-1 expression and

  16. P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling

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    Nomura Seiji

    2007-01-01

    Full Text Available Abstract Background Hyperglycemia or hyperinsulinemia contributes to poorer endometrial cancer survival. It was shown that P-LAP/IRAP translocates to the plasma membrane in response to insulin stimulation. Recently, we demonstrated that P-LAP/IRAP is associated with a poor prognosis in endometrial adenocarcinoma patients. The aim of this study was to examine whether the malignant potential of endometrial cancer enhanced by P-LAP/IRAP is due to increased glucose uptake via the P-LAP/IRAP-mediated activation of insulin signaling. Methods We transfected P-LAP/IRAP cDNA into A-MEC cells (endometrial adenocarcinoma cell line, and A-MEC-LAP cells expressed a remarkably high level of GLUT4 proteins. Results 3H-2-deoxyglucose uptake which responds to insulin in A-MEC-LAP cells was significantly higher than that of A-MEC-pc cells. A-MEC-LAP cells exhibited a significant growth-stimulatory effect compared to A-MEC-pc cells. A-MEC-LAP cells expressed a remarkably high level of p85PI3K protein compared to A-MEC-pc cells, and showed a higher degree of AKT phosphorylation by insulin stimulation. Conclusion In summary, P-LAP/IRAP was involved in the increasing malignant potential of endometrial cancer mediated by insulin. P-LAP/IRAP was suggested to be a potential new target of molecular-targeted therapy for endometrial cancer.

  17. Elevated serum progesterone/ MII oocyte ratio on the day of human chorionic gonadotropin administration can predict impaired endometrial receptivity

    OpenAIRE

    2015-01-01

    Background: Increased serum progesterone on the day of human chorionic gonadotropin administration may affect in vitro fertilization (IVF) outcome. Objective: The aim of this study was to evaluate whether progesterone elevation on the day of human chorionic gonadotropin administration is associated with poor IVF outcome. Materials and Methods: To determine the relationship between serum progesterone on the day of HCG and the outcome of IVF-embryo transfer treatment, 378 infertile patients und...

  18. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by {sup 99m}Tc-MDP bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yang Shunfang [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China)], E-mail: yzyg@sh163.net; Dong Qianggang [Laboratory of Mol-diagnosis, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Yao Ming [Laboratory of Pathology, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Shi Meiping [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Ye Jianding [Department of Radiology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Zhao Langxiang [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Su Jianzhong; Gu Weiyong [Shanghai Thoracic Tumor Institute, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Xie Wenhui [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Wang Kankan; Du Yanzhi [State Key Laboratory of Medical Genomics, Ruijin Hospital of Shanghai Jiaotong University, Shanghai 200025 (China); Li Yao [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China); Huang Yan [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China)], E-mail: huangyan@fudan.edu.cn

    2009-04-15

    Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with {sup 99m}Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with {sup 99m}Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as

  19. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by (99m)Tc-MDP bone scintigraphy.

    Science.gov (United States)

    Yang, Shunfang; Dong, Qianggang; Yao, Ming; Shi, Meiping; Ye, Jianding; Zhao, Langxiang; Su, Jianzhong; Gu, Weiyong; Xie, Wenhui; Wang, Kankan; Du, Yanzhi; Li, Yao; Huang, Yan

    2009-04-01

    Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with (99m)Tc-MDP bone scintigraphy. The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with (99m)Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as an accurate, sensitive, noninvasive tool to detect

  20. Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse

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    Asama Vanichtantikul

    2017-01-01

    Full Text Available Background. Uterine malignancy coexistent with pelvic organ prolapse (POP is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.

  1. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

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    Yinghua Li

    2015-10-01

    Full Text Available Background/Aims: Osteopontin (OPN is an Extracellular Matrix (ECM molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8, Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2 and epithelial-mesenchymal transition (EMT-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT and Extracellular regulated protein kinases (ERK1/2 signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.

  2. Nuclear Factor-κB/p65 (Rel A Is Constitutively Activated in Human Prostate Adenocarcinoma and Correlates with Disease Progression

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    Sanjeev Shukla

    2004-07-01

    Full Text Available Aberrant nuclear factor-κB (NF-κB activation has been implicated in the pathogenesis of several human malignancies. In this study, we determined whether NF-κB is constitutively activated in human prostate adenocarcinoma, and, if so, whether increased NF-κB activation and its binding to DNA influence tumor progression. Using tissue samples obtained during transurethral prostatic resection and paraffin-embedded sections of benign and cancer specimens, we determined the nuclear expression of NF-κB/p65 and NF-κB/p50, cytoplasmic expression of IκBα, its phosphorylation, and expression of NF-κB-regulated genes, specifically Bcl2, cyclin D1, matrix metalloproteinase-9 (MMP-9, and vascular endothelial growth factor (VEGF. A progressive increase in the expression of NF-κB/p65 (but not of p50 was observed in cancer specimens compared to benign tissue, which correlated with increasing levels of IκBa and its phosphorylation. NF-κB DNA-binding activity increased with increasing tumor grade and the binding complex mainly consisted of NF-κB/p65-p50 heterodimers. Immunohistochemical analysis showed enhanced nuclear staining for NF-κB/p65 in both high-grade (P < .0001 and low-grade (P < .003 cancer specimens, compared to benign tissue. The nuclear levels of NF-κB/p65 correlated with concurrent increase in cytosolic levels of IκBa along with NF-κB-dependent expression of Bcl2, cyclin D1, MMP-9, and VEGF. These results demonstrate that NF-κB/p65 is constitutively activated in human prostate adenocarcinoma and is related to tumor progression due to transcriptional regulation of NF-κB-responsive genes.

  3. [P53 protein in adenocarcinoma of the large intestine].

    Science.gov (United States)

    Paluszkiewicz, P; Pawłowska-Wakowicz, B; Cybulski, M; Berbeć, H

    1997-01-01

    P53 gen mutations play significant role in neoplastic transformation of colorectal mucosa. We investigated p53 immunostaining in 80 cases of spontaneous human colorectal adenocarcinomas (with monoclonal DO7 antibody and LSAB+ kit). We found positive, nuclear p53 immunostaining in 64% of nonmucinous adenocarcinoma tissues and in 19% of mucinous adenocarcinomas tissues. P53 protein deposits were most often found in colorectal adenocarcinomas localised in rectum (66.67%) and in advanced (Dukes C, D) colorectal adenocarcinomas (59.38%) as well. There was no statistical significance between the p53 positive immunostaining and the histological differentiation of the colorectal adenocarcinomas. The overall survival of patients with tumours positive for p53 protein was significantly shorter than that of patients with colorectal cancers negative for p53 protein. We conclude that p53 immunohistochemical analysis may be treated as a supplementary prognostic marker for patients with colorectal adenocarcinoma, especially it may be useful for adjuvant therapy selection.

  4. Expression and clinical significance of ghrelin in endometrial hyperplasia and carcinoma of Egyptian patients.

    Science.gov (United States)

    Younes, Sheren Fouad; Aiad, Hayam; Kandil, Mona; El Kalashy, Fatma Samir

    2015-05-01

    Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p = 0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p = 0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.

  5. Liquid-Based Endometrial Cytology Using SurePath™ Is Not Inferior to Suction Endometrial Tissue Biopsy in Clinical Performance for Detecting Endometrial Cancer Including Atypical Endometrial Hyperplasia.

    Science.gov (United States)

    Yanaki, Fumiko; Hirai, Yasuo; Hanada, Azusa; Ishitani, Ken; Matsui, Hideo

    2017-01-01

    We evaluated the clinical performance of liquid-based endometrial cytology (SurePath™) for detecting endometrial malignancies by comparison with the performance of suction endometrial tissue biopsy. From November 2011 to May 2013, we consecutively collected 1,118 liquid-based endometrial cytology specimens and 674 suction endometrial tissue biopsy specimens. The rate of nonpositive final histology in nonpositive liquid-based endometrial cytology (98.2%) was higher than the rate of nonpositive final histology in nonpositive suction endometrial tissue biopsy (97.0%). None of the clinical performance values of liquid-based endometrial cytology for detecting the endometrial malignancies were statistically inferior to those of the suction endometrial tissue biopsy. When the positivity threshold was more than "atypical endometrial cells of undetermined significance," the rate of positive liquid-based endometrial cytology from cases with a positive final histology (84.5%) was higher than the rate of positive suction endometrial tissue biopsy from cases with a positive final histology (69.8%). However, there were still no significant differences among all the performance values. Our liquid-based endometrial cytology would be more appropriate in various clinical situations as the initial detection tool for endometrial malignancies, rather than suction endometrial tissue biopsy. In addition, it could be used in screening for endometrial malignancies on a broader scale. © 2017 S. Karger AG, Basel.

  6. High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells

    Science.gov (United States)

    Khanaki, Korosh; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Darabi, Masoud; Mehdizadeh, Amir; Shabani, Mahdi; Rahimipour, Ali; Nouri, Mohammad

    2014-01-01

    Background: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. Objective: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. Materials and Methods: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. Results: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). Conclusion: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis. PMID:25709631

  7. Human SLURP-1 and SLURP-2 Proteins Acting on Nicotinic Acetylcholine Receptors Reduce Proliferation of Human Colorectal Adenocarcinoma HT-29 Cells.

    Science.gov (United States)

    Lyukmanova, E N; Shulepko, M A; Bychkov, M L; Shenkarev, Z O; Paramonov, A S; Chugunov, A O; Arseniev, A S; Dolgikh, D A; Kirpichnikov, M P

    2014-10-01

    Human secreted Ly-6/uPAR related proteins (SLURP-1 and SLURP-2) are produced by various cells, including the epithelium and immune system. These proteins act as autocrine/paracrine hormones regulating the growth and differentiation of keratinocytes and are also involved in the control of inflammation and malignant cell transformation. These effects are assumed to be mediated by the interactions of SLURP-1 and SLURP-2 with the α7 and α3β2 subtypes of nicotinic acetylcholine receptors (nAChRs), respectively. Available knowledge about the molecular mechanism underling the SLURP-1 and SLURP-2 effects is very limited. SLURP-2 remains one of the most poorly studied proteins of the Ly-6/uPAR family. In this study, we designed for the first time a bacterial system for SLURP-2 expression and a protocol for refolding of the protein from cytoplasmic inclusion bodies. Milligram quantities of recombinant SLURP-2 and its 13C-15N-labeled analog were obtained. The recombinant protein was characterized by NMR spectroscopy, and a structural model was developed. A comparative study of the SLURP-1 and SLURP-2 effects on the epithelial cell growth was conducted using human colorectal adenocarcinoma HT-29 cells, which express only α7-nAChRs. A pronounced antiproliferative effect of both proteins was observed. Incubation of cells with 1 μM SLURP-1 and 1 μM SLURP-2 during 48 h led to a reduction in the cell number down to ~ 54 and 63% relative to the control, respectively. Fluorescent microscopy did not reveal either apoptotic or necrotic cell death. An analysis of the dose-response curve revealed the concentration-dependent mode of the SLURP-1 and SLURP-2 action with EC50 ~ 0.1 and 0.2 nM, respectively. These findings suggest that the α7-nAChR is the main receptor responsible for the antiproliferative effect of SLURP proteins in epithelial cells.

  8. Monitoring of TGF-β 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device.

    Science.gov (United States)

    Li, Yuan; Gao, AnXiu; Yu, Ling

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. It is believed that EMT is associated with initiation and completion of the invasion-metastasis cascade. In this study, an economic approach was developed to fabricate a microfluidic device with less instrumentation requirement for the investigation of EMT by quantifying cell adhesion force. Fluid shear force was precisely controlled by a homemade microfluidic perfusion apparatus and interface. The adhesion capability of the human lung adenocarcinoma cell line A549 on different types of extracellular matrix protein was studied. In addition, effects of transforming growth factor-β (TGF-β) on EMT in A549 cells were investigated by characterizing the adhesion force changes and on-chip fluorescent staining. The results demonstrate that the microfluidic device is a potential tool to characterize the epithelial-mesenchymal transition process by measuring cell adhesion force.

  9. Induction of Apoptosis in Human Breast Adenocarcinoma Cells MCF-7 by Monapurpyridine A, a New Azaphilone Derivative from Monascus purpureus NTU 568

    Directory of Open Access Journals (Sweden)

    Tzu-Ming Pan

    2012-01-01

    Full Text Available A new azaphilonidal derivative, monapurpyridine A (MPA, has recently been isolated from the fermented products of Monascus purpureus NTU 568. The structure of MPA was elucidated by nuclear magnetic resonance (1H-NMR, 13C-NMR, COSY, HMQC, and HMBC and other spectroscopic analyses. Biological evaluation revealed that MPA could induce cell death in human breast adenocarcinoma cells MCF-7, and it has no significant toxicity to normal mammary epithelial cells M10. The MTT assay and flow cytometric analysis were employed to investigate cell viability and cell cycle influenced by MPA. Moreover, we used Western blot and caspase activity assay to demonstrate the activation of caspase-3, -8 and -9 resulted from MPA. All evidence supported that MPA was suitable for developing into a chemotherapeutic or chemopreventive agent against breast cancer.

  10. Clinicopathological features and treatment of extremity bone metastasis in patients with endometrial carcinoma: a case report and review

    Institute of Scientific and Technical Information of China (English)

    JIANG Guo-qing; GAO Yu-nong; GAO Min; ZHENG Hong; YAN Xin; WANG Wen; AN Na; CAO Kun

    2011-01-01

    Unlike other non-gynecologic solid tumors, such as breast cancer, lung cancer, metastasis to bone from endometrial carcinoma is rare, metastasis to extremity is extremely rare. We report a 51-year-old multiparous woman with FIGO Stage IVb Grade 2 endometrial adenocarcinoma which metastasized to left lower extremity bone. She received an amputation of left lower extremity below the knees, and a total abdominal hysterectomy and bilateral salpingo-oophorectomy, and followed by systemic chemotherapy, radiation therapy to the pelvis and progestational agent. She had a complete response to above treatments, and disease-free survival for 10 months. After recurrence, she received chemotherapy, radiotherapy and progestational agent once again. She had lived 56 months and is still alive by the time of report. Metastasis of endometrial carcinoma to extremity bone can rarely occur and should be considered when the patient with endometrial carcinoma complained of unexplained pain and swelling associated with extremity bone.

  11. Establishment of a Multidrug Resistance Cell Line A549/cDDP of Human Lung Adenocarcinoma and Expression Analysis of Multidrug Resistance-Associated Genes

    Directory of Open Access Journals (Sweden)

    Yongcheng PAN

    2009-03-01

    Full Text Available Background and objective It has been proven that chemotherapy failure caused by multidrug resistance in lung tumor cells is the main cause for the patient's survival rate. The aim of this study is to establish a multidrug resistance cell line of human lung adenocarcinoma and study the mechanism of multidrug resistance. Methods Human lung adenocarcinoma cell line A549 was induced to multidrug resistance cell line A549/cDDP by intermittentadministration of high dose of cisplatin (cDDP. The multidrug resistance was detected by using MTT assay. The levels of expression of MDR-1 gene-coded P-glycoportein (P-gp, multidrug resistance-associated protein (MRP, and GSH/GST were examined by flow cytometric assay. The levels of expression of MDR and MRP gene were also detected by RTPCR in both A549/cDDP and A549 cell lines. Results A549/cDDP was resistant to many anti-tumor agents. The IC50 of A549/cDDP was 16.87 times higher than that of A549. The expressions of P-gp and MRP in A549/cDDP were increased significantly to (70.5±4.9% and (29.4±2.9%, respectively, vs (42.4±5.6% and (21.4±3.5% in A549. There was no difference of the GSH/GST expression between A549/cDDPand A549 cells. Conclusion A549/cDDP is a model with multidrug resistance and the levels of MDR and MRP mRNA expressions are remarkably higher in A549/cDDP than those in A549.

  12. Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells

    Directory of Open Access Journals (Sweden)

    Kuen-daw Tsai

    2016-06-01

    Full Text Available Background: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. Methods: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA, a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs were determined by neutral red staining. Results: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm loss, activation of both caspase-3 and -9, increase of annexin V+PI+ cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. Conclusions: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown. Our data implicate

  13. Diagnostic test of endometrial cytobrush in cases of perimenopausal and postmenopausal hemorrhage

    Directory of Open Access Journals (Sweden)

    Andrijono Andrijono

    2005-06-01

    Full Text Available Perimenopausal menopausal hemorrhage can be due to by a variety of causative factors. One of its dangerous causes is atypical hyperplasia and endometrial carcinoma. There are a number of risk factors for the occurrence of endometrial carcinoma. The group that has this risk belongs to high-risk group. In this high-risk group, it is necessary to have a method to identify the changes in endometrial abnormality. One of the alternatives is the examination of endometrial cytology. The objective of this study was to evaluate the sensitivity, specificity and correlation test between endometrial cytology and endometrial histology. This study was a diagnostic test of cytological examination of the endometrium as compared with endometrial histology. Endometrial cytology was performed with a modification of cytubrush and IUD shell. Specimen was dissolved into the centrifuged NaCl, and its deposits were then processed for cytological examination with Papanicolaou and Giemsa staining. After the taking of cytology, the process was continued with curettage of the endometrium, and the specimens were processed for cytological examination. Both of them were examined by anatomic pathologist. Statistical analysis used diagnostic test using histological examination of curetage specimens as gold standard. During the period of study 45 study samples were collected, among which 12 (26.66% were endometrial adenocarcinoma, 6 (13.33% with atypical hyperplasia, 11 (24.44% with non-atypical hyperplasia, 15 (33.33% were samples without abnormality, and one sample with endometritis. Actual correlation value was 57.8%, correlation because of possibility 3.38%, and correlation not because of possibility 54.42%, potential correlation not because of possibility 96.62%, and Kappa value 0.56. It was concluded that cytological examination of the endometriurn with cytobrush could be employed as a screening method in the abnormalities of endometrial thickness, with

  14. Expression Levels of RFP in Normal and Cancer Human Tissues via Real-time RT-PCR Detection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Ret finger protein(RFP) is a member of the tripartite motif family, which is characterized by a conserved RING finger of motif, a B-box, and a coiled-coil domain(they are called RBCC generally). Although RFP was known to be an oncogene when its RBCC moiety was connected with a tyrosine kinase domain by DNA rearrangement, its biological function was not well defined. In this study, by using real-time RT-PCR, the RFP expressions in human and mouse normal tissues, and in the cervical squamous cell carcinoma, endometrial adenocarcinoma, gastric adenocarcinoma, esophageal squamous cell carcinoma, and brain cancer tissues were analyzed. The result of the study proved that the highest level of mRNA reverse transcription appeared in the normal testical tissue, whereas that in other normal tissues of human and mice were low. The mRNA reverse transcription level of RFP was higher in the endometrial adenocarcinoma tissue than in the cervical squamous cell carcinoma tissue; the mRNA reverse transcription level of RFP in the gastric adenocarcinoma tissue was significantly higher than that in the esophageal squamous cell carcinoma tissue. It was also found that the mRNA reverse transcription level of RFP in the brain cancer tissue was higher than that in the normal brain tissue. These results suggested that RFP could possibly be a useful molecular target for the development of new therapeutics for malignant tumors.

  15. Interphase cytogenetics of prostatic adenocarcinoma

    OpenAIRE

    Alers, Janneke

    1997-01-01

    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of (cyto)genetic aberrations occurring in prostatic cancer is given. The third part of this introduction will discuss methodological aspects of this thesis, i.e., the development and methodology of no...

  16. Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia().

    Science.gov (United States)

    Marnach, Mary L; Butler, Kristina A; Henry, Michael R; Hutz, Catherine E; Langstraat, Carrie L; Lohse, Christine M; Casey, Petra M

    2017-04-01

    Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m(2) vs. 31 kg/m(2); p < 0.001). Among 332 women with follow-up endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometrial hyperplasia) resolved in 83% and 87% of patients, respectively (p = 0.31). Rates of resolution of EIN subcategory 2 (endometrial intraepithelial neoplasia) were also similar between groups (68% vs. 62%; p = 0.82). In women with EIN subcategory 3 (endometrial adenocarcinoma), 22% of those using LNG IUS and one of two women treated with OP had resolution of disease as of last follow-up. OP and LNG IUS offer similar endometrial protection for women with EIN. LNG IUS offers convenience, minimal adverse effects, reversibility, and long-term endometrial protection.

  17. Correlation of bleeding pattern with endometrial histopathologic results in perimenopausal women with abnormal uterine bleeding

    Directory of Open Access Journals (Sweden)

    Zehra Yilmaz

    2015-06-01

    Full Text Available Background: Abnormal Uterine Bleeding (AUB is referred as bleeding outside of normal menstruation pattern and it is the most common gynecological problem for women of all ages. This study was evaluated the correlation of menstrual bleeding patterns and endometrial histopathological findings in perimenopausal women. Methods: This study was done on perimenopausal aged women presented with AUB for the last 6 months at a gynecology clinic of a tertiary medical center. Only the patients with isolated endometrial causes of AUB were selected for study. A total of 313 cases were included in the study. Abnormal bleeding patterns of the patients were recorded and endometrial sampling was performed to all women. AUB was classified as menorrhagia, metrorrhagia, menometrorrhagia, polymenorrhea, intermenstrual bleeding, and histopathological findings were classified as Proliferative Endometrium (PE, Secretory Endometrium (SE, Disordered Proliferative Pattern (DPP, Endometrial Polyp (EP, Chronic Endometritis (CE, Endometrial Hyperplasia (EH, and Endometrial Adenocarcinoma (CA. Results: The most common bleeding pattern was menorrhagia (45.0% and the most common histopathological finding was PE+SE (52.0% in our study. PE+SE and endometrial hyperplasia without atypia were found more common in menorrhagia group. The most histopathological findings were found PE+SE in menometrorrhagia and polymenorrhea group (P 0.05. Conclusions: We concluded that although menometrorrhagia and polymenorrhea were significantly more associated with PE+SE, intermenstrual bleeding was significantly more associated with EP and CE. It is noteworthy that endometrial hyperplasia without atypia is significantly higher in patients with menorrhagia which is the most common abnormal bleeding pattern in perimenopausal aged women. [Int J Reprod Contracept Obstet Gynecol 2015; 4(3.000: 547-550

  18. A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer.

    Science.gov (United States)

    Gunter, Marc J; Hoover, Donald R; Yu, Herbert; Wassertheil-Smoller, Sylvia; Manson, Joann E; Li, Jixin; Harris, Tiffany G; Rohan, Thomas E; Xue, Xiaonan; Ho, Gloria Y F; Einstein, Mark H; Kaplan, Robert C; Burk, Robert D; Wylie-Rosett, Judith; Pollak, Michael N; Anderson, Garnet; Howard, Barbara V; Strickler, Howard D

    2008-04-01

    Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HR(q4-q1)), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HR(q4-q1), 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HR(q4-q1), 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data.

  19. Complications of pelvic and para-aortic lymphadenectomy in patients with endometrial cancer.

    Science.gov (United States)

    Arduino, S; Leo, L; Febo, G; Tessarolo, M; Wierdis, T; Lanza, A

    1997-01-01

    The International Federation of Gynecology and Obstetrics (FIGO) changed the staging criteria for endometrial cancer in 1988 and adopted a surgical-pathological staging involving also pelvic and/or para-aortic lymphadenectomy. A total of 236 patients were treated for endometrial adenocarcinoma at Department B of the Gynecologic and Obstetrics Institute, University of Turin, between January 1976 and December 1995. Our protocol for surgical staging always entails pelvic and para-aortic lymphadenectomy and a simple total hysterectomy and bilateral adnexectomy with removal of the upper third of the vagina. The aim of this study was to carry out a retrospective evaluation of the morbidity in patients with endometrial cancer after surgical treatment, either TAH-BSO alone or TAH-BSO with pelvic and para-aortic lymphadenectomy.

  20. Cystic endometrial hyperplasia and pyometra in three captive African hunting dogs (Lycaon pictus).

    Science.gov (United States)

    Jankowski, Gwen; Adkesson, Michael J; Langan, Jennifer N; Haskins, Samantha; Landolfi, Jamie

    2012-03-01

    Pyometra and cystic endometrial hyperplasia are common in domestic canids and are suspected to develop as a consequence of elevated progesterone levels. Reports of uterine pathology in exotic canids are limited, with some speculating of association with contraception. This report describes pyometra, cystic endometrial hyperplasia, and ovariohysterectomy in three African hunting dogs (Lycaon pictus). Ovarian corpora lutea were detected in two of the dogs, suggesting endogenous progesterone production. One dog had a uterine adenocarcinoma and two had ovarian granulosa cell tumors. Clinical signs included anorexia, lethargy, vulvar discharge, polyuria, polydipsia, and abdominal distention. Diagnosis was based on clinical signs, physical examination, bloodwork, radiography, and ultrasonography, with confirmation through histopathologic evaluation of tissues. Cystic endometrial hyperplasia, pyometra, and uterine neoplasia have rarely been diagnosed in exotic canids; however, they should be considered as differential diagnoses in intact bitches that present with suspected reproductive disease.

  1. Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer

    Science.gov (United States)

    Draghini, Lorena; Casale, Michelina; Trippa, Fabio; Anselmo, Paola; Arcidiacono, Fabio; Fabiani, Stefania; Italiani, Marco; Chirico, Luigia; Muti, Marco

    2017-01-01

    Purpose To report our experience on high-dose-rate brachytherapy (HDR-BT) in patients with stage I-III endometrial cancer unfit to surgery. Material and methods Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95), median Karnofsky performance status 90% (range, 60-100). Histology was endometrial adenocarcinoma in 14 (82%), and non-endometrial in 3 (18%) patients. In 15 (88%) patients, clinical stage was I and in remaining 2 (12%) was III. All patients were evaluated with computed tomography (CT) and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC) was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. Results Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT) combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131), 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS) at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adenocarcinoma) LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma) was 100% at 1 and 6 years (p = 0.05). Two (12%) patients had G2 acute toxicity and two others (12%) G1 late toxicity. Conclusions Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection), it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology. PMID:28533799

  2. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Shang-Jyh [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Su, Jen-Liang [Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung, Taiwan (China); Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan (China); Department of Biotechnology, Asia University, Taichung, Taiwan (China); Chen, Chi-Kuan [Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua [Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Bien, Mauo-Ying [School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Yang, Shun-Fa [Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chien, Ming-Hsien, E-mail: mhchien1976@gmail.com [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2012-05-15

    The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. -- Highlights: ► Osthole treatment inhibits lung adenocarcinoma cells migration and invasion. ► Osthole reduces the expression and proteolytic activity of MMP-9. ► Osthole inhibits MMP-9 transcription via suppression of NF-κB binding activity. ► Osthole

  3. Aression of TLR9 in human pulmonary adenocarcinoma cell line A549%TLR9在人肺腺癌细胞A549中的表达

    Institute of Scientific and Technical Information of China (English)

    Jun Yu; Tiecheng Pan; Xiang Wei; Ligang Liu; Min Hu; Fang Yuan; Jiaduo Li

    2009-01-01

    Objective: Being considered as a bridge between the innate immunity and acquired immunity, Toll-like receptors (TRLs) are very important innate immunity moleculars. Recent researchs on the innate immunity have focused on the relation- ship between TLRs and human tumor. This paper investgated the expression and significance of TLR9 in human pulmonary adenocarcinoma cell (A549 cell) and human bronchial epithelial cell (HBE cell). Methods: After culturing A549 cell and HBE cell in vitro, the expression of TLR9 mRNA and protein in both cells were detected by immunocytochemistry, Real-time Quantitative Reverse Transcriptase-Polymerase Chain Reaction (Real-time Quantitative PCR) and Western blot, respectively. Results: By immunocytochemistry staining, TLR9 was mainly expressed in both cells' cell membrane and endochylema as brown-yellow material. It showed that the expressions of TLR9 mRNA and protein in A549 cell were stronger than those in HBE cell (P < 0.01). Conclusion: The results suggest TLR9 might cause the progression of human pulmonary adenocaroinoma, and the mechanism needs to be further investgatied.

  4. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  5. Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy

    DEFF Research Database (Denmark)

    Horne, A W; Duncan, W C; King, A E;

    2009-01-01

    Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized...... chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P ... to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression...

  6. Protein Kinase C alpha (PKCα) dependent signaling mediates endometrial cancer cell growth and tumorigenesis

    Science.gov (United States)

    Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.

    2009-01-01

    Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862

  7. EphrinA1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells.

    Science.gov (United States)

    Fujii, Haruko; Fujiwara, Hiroshi; Horie, Akihito; Suginami, Ko; Sato, Yukiyasu; Konishi, Ikuo

    2011-05-01

    Recently, the Eph-ephrinA system was proposed to contribute to the initial interaction between the maternal endometrial epithelium and embryonic trophectoderm. Since the Eph-ephrin interaction can induce adhesive and/or repulsive forces into the cells, we examined the possible role of this system in functional changes in endometrial epithelial cells using endometrial carcinoma-derived Ishikawa cells. The expressions of EphA1, A2 and A4 on Ishikawa cells were examined by RT-PCR and western blotting analyses. The effects of recombinant ephrinA1 on Ishikawa cells were also examined by western blot analysis and cell attachment and aggregation assays. EphA1, A2 and A4 were expressed on Ishikawa cells. Recombinant ephrinA1 bound to the surfaces of Ishikawa cells and induced phosphorylation of EphA2 and A4. In bovine serum albumin-blocked nitrocellulose-coated dishes, Ishikawa cells remained floating and aggregated with each other. Under these conditions, immobilized ephrinA1 promoted Ishikawa cell attachment with increased tyrosine phosphorylation in focal adhesion kinase. In addition, immobilized ephrinA1 reversibly inhibited Ishikawa cell aggregation. Gene-reduction of EphA1, A2 and A4 by siRNAs attenuated the inhibitory effects of ephrinA1 on cell aggregation, confirming that ephrinA1 affects Ishikawa cell functions through Eph-ephrinA interaction. This study demonstrated that the Eph-ephrinA system can promote cell attachment along with intercellular dissociation in Ishikawa cells. These findings suggest that this system can induce functional changes in endometrial epithelial cells.

  8. Synchronous rectal adenocarcinoma and anal canal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    GU Jin; LI Jiyou; YAO Yunfeng; LU Aiping; WANG Hongyi

    2007-01-01

    It is difficult to distinguish a tectal carcinoma with anal metastases from coexistent synchronous anorectal carcinomas.The therapeutic strategy for rectal and anal carcinoma is so different that it should be clearly identified.Here,we report on the case of a 63-year-old man who presented with an upper-third rectal adenocarcinoma.Five months after resection,he developed an adenocarcinoma in the anal canal.The histological slides of both tumors were reviewed and immunohistochemical studies for cytokeratins(CKs)7 and 20 were performed.The index tumor demonstrated CK 7-/CK 20+and the second showed CK7+/CK20+.For this reason,we believe the present case had synchronous adenocarcinomas arising from anal canal and the rectum separately.It is very important to difierentiate the anorectal lesions pathologically because of the impact on the therapeutic options available,especially for the lesion arising in the anal canal.

  9. Atypical endometrial cells and atypical glandular cells favor endometrial origin in Papanicolaou cervicovaginal tests: Correlation with histologic follow-up and abnormal clinical presentations

    Directory of Open Access Journals (Sweden)

    Longwen Chen

    2014-01-01

    Full Text Available The 2001 Bethesda system recommends further classifying atypical glandular cells (AGCs as either endocervical or endometrial origin. Numerous studies have investigated the clinical significance of AGC. In this study, we investigated the incidence of clinically significant lesions among women with liquid-based Papanicolaou cervicovaginal (Pap interpretations of atypical endometrial cells (AEMs or AGC favor endometrial origin (AGC-EM. More importantly, we correlated patients of AEM or AGC-EM with their clinical presentations to determine if AEM/AGC-EM combined with abnormal vaginal bleeding is associated with a higher incidence of significant endometrial pathology. All liquid-based Pap tests with an interpretation of AEM and AGC-EM from July, 2004 through June, 2009 were retrieved from the database. Women with an interpretation of atypical endocervical cells, AGC, favor endocervical origin or AGC, favor neoplastic were not included in the study. The most severe subsequent histologic diagnoses were recorded for each patient. During this 5-year period, we accessioned 332,470 Pap tests of which 169 (0.05% were interpreted as either AEM or AGC-EM. Of the 169 patients, 133 had histologic follow-up within the health care system. The patients ranged in age from 21 to 71 years old (mean 49.7. On follow-up histology, 27 (20.3% had neoplastic/preneoplastic uterine lesions. Among them, 20 patients were diagnosed with adenocarcinoma (18 endometrial, 1 endocervical, and 1 metastatic colorectal, 3 with atypical endometrial hyperplasia, and 4 with endometrial hyperplasia without atypia. All patients with significant endometrial pathology, except one, were over 40 years old, and 22 of 25 patients reported abnormal vaginal bleeding at the time of endometrial biopsy or curettage. This study represents a large series of women with liquid-based Pap test interpretations of AEM and AGC-EM with clinical follow-up. Significant preneoplastic or neoplastic endometrial

  10. Effect of CCR7, CXCR4 and VEGF-C on the lymph node metastasis of human pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Guo, Jinghui; Lou, Wenhui; Ji, Yuan; Zhang, Shuncai

    2013-05-01

    The aim of the present study was to investigate the association between the expression of chemokine receptors CCR7 and CXCR4 and vascular endothelial growth factor (VEGF)-C and the lymph node metastasis of pancreatic ductal adenocarcinoma (PDAC). The mRNA transcription levels of CCR7, CXCR4 and VEGF-C were measured in 24 specimens by real-time reverse transcription (RT)-PCR, while the protein expression levels were measured in 65 specimens by immuohistochemistry. Professional software for pathological image manipulation (Image Pro Plus 6.0) was used to quantitate the results of the immunohistochemical staining. The mRNA and protein expression levels of CCR7, CXCR4 and VEGF-C were all significantly higher in the cancer samples compared with those in the adjacent normal tissue. The CCR7 and VEGF-C mRNA and protein expression levels were significantly higher in the patients with cancer types exhibiting lymph node metastasis and an advanced International Union Against Cancer (UICC) stage (PCCR7 expression (PCCR7 and VEGF-C (P0.05), however the strong positive expression of CCR7 and VEGF-C was significantly associated with the lymph node metastasis of PDAC.

  11. Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Ji, Li; Gong, Chen; Ge, Liangyu; Song, Linping; Chen, Fenfen; Jin, Chunjing; Zhu, Hongyan; Zhou, Guoxiong

    2017-01-01

    Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets.

  12. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

    Directory of Open Access Journals (Sweden)

    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  13. Fisetin induces G2/M phase cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation in human endometrial cancer cells

    Directory of Open Access Journals (Sweden)

    Zhan-Ying Wang

    2015-06-01

    Full Text Available Endometrial cancer is one of the most prevalent gynaecological malignancies where, currently available therapeutic options remain limited. Recently phytochemicals are exploited for their efficiency in cancer therapy. The present study investigates the anti-proliferative effect of fisetin, a flavonoid on human endometrial cancer cells (KLE and Hec1 A. Fisetin (20-100 µM effectively reduced the viability of Hec1 A and KLE cells and potentially altered the cell population at G2/M stage. Expression levels of the cell cycle proteins (cyclin B1, p-Cdc2, p-Cdc25C, p-Chk1, Chk2, p-ATM, cyclin B1, H2AX, p21 and p27 were analyzed. Fisetin suppressed cyclin B1 expression and caused inactiva-tion of Cdc25C and Cdc2 by increasing their phosphorylation levels and further activated ATM, Chk1 and Chk2. Increased levels of p21 and p27 were observed as well. These results suggest that fisetin induced G2/M cell cycle arrest via inactivating Cdc25c and Cdc2 through activation of ATM, Chk1 and Chk2.

  14. BIOPSIA ENDOMETRIAL AMBULATORIA: EXPERIENCIA PRELIMINAR

    OpenAIRE

    Domínguez C,Claudio; Zamora F,Jessica; Barrera P,Sandra; Tacla F,Ximena

    2006-01-01

    Objetivo: Presentar la experiencia inicial en el diagnóstico histológico con biopsia endometrial ambulatoria obtenida con pipelle de Cornier. Material y método: Se efectuó biopsia endometrial ambulatoria con pipelle de Cornier en 144 pacientes con sospecha clínica y/o ecográfica de patología endometrial difusa. Resultados: Se logró realizar el procedimiento a 131 pacientes (91%), obteniéndose diagnóstico histológico satisfactorio en 110 casos (76,4%). De las 110 muestras analizadas, se diagno...

  15. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  16. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Science.gov (United States)

    Hong, Jie; Li, Dan; Cao, Weibiao

    2016-01-01

    Mechanisms of the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  17. Grape waste extract obtained by supercritical fluid extraction contains bioactive antioxidant molecules and induces antiproliferative effects in human colon adenocarcinoma cells.

    Science.gov (United States)

    Lazzè, Maria Claudia; Pizzala, Roberto; Gutiérrez Pecharromán, Francisco Javier; Gatòn Garnica, Paloma; Antolín Rodríguez, Juan Manuel; Fabris, Nicola; Bianchi, Livia

    2009-06-01

    Grape waste management is one of the main problems of winery industries, but, conversely, grape waste contains a high amount of polyphenols that might protect against human diseases related to oxidative stress, such as colorectal cancer. Therefore, the aim of this work was to investigate the antioxidant and antiproliferative activities of a grape waste extract obtained by supercritical fluid extraction. Because the beneficial effect of grape is related to its content of polyphenolic molecules, the extract was chemically characterized by high-performance liquid chromatography in order to assess its major bioactive components. The antioxidant activity of the grape extract was determined. The results showed that the grape extract presents a strong antiradical activity in the in vitro 2,2-diphenyl-1-picrylhydrazyl radical assay and protects against reactive oxygen species production in human colon adenocarcinoma cells (Caco-2). In contrast, the extract did not protect in the citronellal thermooxidation system and showed a weak protective action against lipid peroxidation in Caco-2 cells. The clonogenic assay and the cell cycle distribution analysis showed that the grape extract has a significant antiproliferative effect in a tumor cell line. These data indicate that grape extract is a promising product to be used as an anti-free radical agent and could exert a chemopreventive action.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. The lectin BJcuL induces apoptosis through TRAIL expression, caspase cascade activation and mitochondrial membrane permeability in a human colon adenocarcinoma cell line.

    Science.gov (United States)

    Damasio, Danusa de Castro; Nolte, Stefanie; Polak, Leonardo Puchetti; Brandt, Anna Paula; Bonan, Natália Borges; Zischler, Luciana; Stuelp-Campelo, Patrícia M; Cadena, Silvia Maria S C; Noronha, Lúcia de; Elífio-Esposito, Selene L; Moreno-Amaral, Andréa Novais

    2014-11-01

    It has been demonstrated that the cytotoxic effect of BJcuL, the lectin isolated from Bothrops jararacussu venom, on human gastric carcinoma is accompanied by the inhibition of extracellular matrix adhesion, cytoskeleton disassembly and apoptosis induction. The present study aimed to evaluate the apoptosis mechanisms triggered by the BJcuL interaction with specific glycans on the surface of HT29 human colon adenocarcinoma cells. The results demonstrated that BJcuL interacts with glycoligands targets on the cell, which were inhibited in the presence of d-galactose. It shows a dose-dependently cytotoxic effect that is inhibited in the presence of d-galactose. A dose-dependent cell aggregation decrease was also observed for the HT29 cells. Analysis of cell proliferation inhibition was assessed by anti-PCNA and demonstrated that lectin diminishes PCNA expression when compared with untreated cells. Differences in apoptotic marker expression estimated by immunohistochemistry revealed that the lectin promotes an increase in TRAIL expression, leading to an increase in the expression of FADD, caspase-8 and Bax. Besides the increased expression of apoptosis-related proteins, our results revealed that the lectin promotes a mitochondrial respiration decrease and a 75% increase in the amount of cytochrome c released. Together these results suggest that the cytotoxicity of BJcuL can sensitize pro-apoptotic proteins in the cytoplasm and mitochondria, leading to the apoptotic cascade.

  20. Dealcoholized Korean Rice Wine (Makgeolli) Exerts Potent Anti-Tumor Effect in AGS Human Gastric Adenocarcinoma Cells and Tumor Xenograft Mice.

    Science.gov (United States)

    Shin, Eun Ju; Kim, Sung Hee; Kim, Jae Ho; Ha, Jaeho; Hwang, Jin-Taek

    2015-09-01

    Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.

  1. Claudin-18 inhibits cell proliferation and motility mediated by inhibition of phosphorylation of PDK1 and Akt in human lung adenocarcinoma A549 cells.

    Science.gov (United States)

    Shimobaba, Shun; Taga, Saeko; Akizuki, Risa; Hichino, Asami; Endo, Satoshi; Matsunaga, Toshiyuki; Watanabe, Ryo; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Sugatani, Junko; Ikari, Akira

    2016-06-01

    Abnormal expression of claudin subtypes has been reported in various cancers. However, the pathological role of each claudin has not been clarified in detail. Claudin-18 was absent in human non-small cell and small cell lung cancers, although it is expressed in normal lung tissues. Here, we examined the effect of claudin-18 expression on the expression of junctional proteins, cell proliferation, and cell motility using human lung adenocarcinoma A549 cells. Real-time PCR and western blotting showed that exogenous expression of claudin-18 had no effect on the expression of junctional proteins including claudin-1, zonula occludens-1 (ZO-1), occludin, and E-cadherin. Claudin-18 was mainly distributed in cell-cell contact areas concomitant with ZO-1. Cell proliferation was significantly decreased at 48 and 72h after seeding of claudin 18-expressing cells. Claudin-18 suppressed cell motility, whereas it increased cell death in anoikis. Claudin-18 decreased phosphorylated (p)-3-phosphoinositide-dependent protein kinase-1 (PDK1) and p-Akt levels without affecting p-epidermal growth factor receptor and p-phosphatidylinositol-3 kinase (PI3K) levels. Furthermore, claudin-18 was bound with PDK1 and suppressed the nuclear localization of PDK1. We suggest that claudin-18 suppresses the abnormal proliferation and motility of lung epithelial cells mediated by inhibition of the PI3K/PDK1/Akt signaling pathway.

  2. Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du

    2004-01-01

    AIM: To investigate the effects of mifepristone on the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 and its mechanisms.METHODS: After incubation with various concentrations of mifepristone (5, 10, 20 μmol/L), the adhesion to artificial basement membrane, Matrigel, and the migration of MKN-45cells were assayed using MTT assay and lranswell cell culture chambers, respectively. Enzyme- linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine the expression of vascular endothelial growth factor (VEGF)and integrin β3 in the cells. After subcutaneous transplantation of MKN-45 cells in nude mice, mifepristone (50 mg/kg.d)was administrated subcutaneously for 8 wk to assess its effects on tumor metastasis. Immunohistochemical analysis was used to detect the expression of VEGF and microvascular density (MVD) in xenografted tumors.RESULTS: Mifepristone dose-dependently inhibited the heterotypic adhesion to Matrigel of MKN-45 cells. The inhibition was accompanied by a significant down-regulation of integrin β3 expression in the cells. After incubation with 5, 10, 20 μmol/L mifepristone, the number of migrated MKN-45 cells was 72±8, 50±6, 41±5 in experiment group, and 94±16 in control group (P<0.01). Meanwhile, secreted VEGF protein of MKN-45 cells in mifepristone-treated group (14.2±2.9, 8.9±3.1, 5.4±2.1 ng/g per liter) was significantly lower than that in control group (22.7±4.3 ng/g per liter,P<0.01). In vivo, mifepristone decreased the number of metastatic foci in lungs of nude mice and down-regulated the expression of VEGF and MlVD in the xenograted tumors.CONCLUSION: Mifepristone can effectively inhibit the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45in vitro and in vivo through inhibition of heterotypic adhesion to basement membrane,cell migration and angiogenesis.

  3. Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Gestl, Erin E., E-mail: egestl@wcupa.edu [Department of Biology, West Chester University, 750 S Church Street, West Chester, PA 19383 (United States); Anne Boettger, S., E-mail: aboettger@wcupa.edu [Department of Biology, West Chester University, 750 S Church Street, West Chester, PA 19383 (United States)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Eight human colorectal cell lines were evaluated for p53 and mortalin localization. Black-Right-Pointing-Pointer Six cell lines displayed cytoplasmic sequestration of the tumor suppressor p53. Black-Right-Pointing-Pointer Direct interaction between mortalin and p53 was shown in five cell lines. Black-Right-Pointing-Pointer Cell lines positive for p53 sequestration yielded elevated p53 expression levels. Black-Right-Pointing-Pointer This study yields the first evidence of cytoplasmic sequestration p53 by mortalin. -- Abstract: While it is known that cytoplasmic retention of p53 occurs in many solid tumors, the mechanisms responsible for this retention have not been positively identified. Since heatshock proteins like mortalin have been associated with p53 inactivation in other tumors, the current study sought to characterize this potential interaction in never before examined colorectal adenocarcinoma cell lines. Six cell lines, one with 3 different fractions, were examined to determine expression of p53 and mortalin and characterize their cellular localization. Most of these cell lines displayed punctate p53 and mortalin localization in the cell cytoplasm with the exception of HCT-8 and HCT116 379.2 cells, where p53 was not detected. Nuclear p53 was only observed in HCT-116 40-16, LS123, and HT-29 cell lines. Mortalin was only localized in the cytoplasm in all cell lines. Co-immunoprecipitation and immunohistochemistry revealed that p53 and mortalin were bound and co-localized in the cytoplasmic fraction of four cell lines, HCT-116 (40-16 and 386; parental and heterozygous fractions respectively of the same cell line), HT-29, LS123 and LoVo, implying that p53 nuclear function is limited in those cell lines by being restricted to the cytoplasm. Mortalin gene expression levels were higher than gene expression levels of p53 in all cell lines. Cell lines with cytoplasmic sequestration of p53, however, also displayed elevated p53

  4. 咪唑诱导的人子宫内膜癌细胞HEC-1B空泡化现象研究%Study on the Vacuolation of Imidazole-Treated Human Endometrial Carcinoma Cell Line HEC-1B

    Institute of Scientific and Technical Information of China (English)

    张玖航; 曾申明

    2011-01-01

    As a kind of weak bases, imidazole cause vacuolation of animal endometrial cells, and affect the physiological and reproductive functions. Our study discuss the mechanism of vacuolation after treatment with imidazole through experimental model of human endometrial carcinoma cell line HEC -IB. We study through Genechip research, fluorescence quantitative PCR and observation of laser confocal microscopy. Results: Genechip research results show that gene of subunit V0D2 of human vacuolar type H+-ATPase (V-ATPase) had an increased expression after the treatment with imidazole on human endometrial carcinoma cell line HEC -IB. Genechip research results were verified by fluorescence quantitative PCR. The expression of the mRNA of subunit V0D2 of human V -ATPase increased.Another subunit V1E1 of human V-ATPase also had an increased expression by fluorescence quantitative PCR. Bafilomycin Al, an inhibitor of V-ATPase, significantly inhibited the vacuolation caused by imidazole. The phenomenon was observed by laser confocal microscopy after staining human endometrial carcinoma cell line HEC-IB with Acridine orange. These results suggest that V-ATPase plays an important role in cell vacuolation caused by imidazole.%咪唑作为一种弱碱性物质,处理动物子宫内膜细胞后,可诱导其产生空泡化现象,进而影响其生殖生理功能.本研究使用人子宫内膜癌细胞HEC-1B作为模型,使用咪唑处理导致细胞空泡化后探讨空泡化产生的生理机制.通过基因芯片分析、荧光定量PCR检测、激光共聚焦显微镜观察等方法进行研究.结果表明:咪唑处理人子宫内膜癌细胞HEC-1B后,空泡型质子泵(V-ATPase)亚基VOD2基因表达量上调.使用荧光定量PCR验证芯片结果,V-ATPase亚基VOD2mRNA表达量有所上调.对V-ATPase另外一个亚基V1E1基因进行荧光定量PCR,其mRNA表达量也有所上调.使用V-ATPase抑制剂巴弗洛霉素A1和咪唑共同处理人子宫内膜癌细胞HEC-1B后,通过

  5. Postoperative radiotherapy for endometrial cancer

    National Research Council Canada - National Science Library

    Choi, Eun Cheol; Kim, Jin Hee; Kim, Ok Bae; Byun, Sang Jun; Park, Seung Gyu; Kwon, Sang Hoon

    2012-01-01

    .... Sixty four patients with stage I-III endometrial cancer (EC) treated with postoperative radiotherapy alone between January 1989 and December 2008 at the Keimyung University Dongsan Medical Center were chosen for the present study...

  6. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  7. Risks of Endometrial Cancer Screening

    Science.gov (United States)

    ... Transvaginal ultrasound Endometrial sampling Tests are used to screen for different types of cancer. Some screening tests ... endometrium by inserting a brush, curette , or thin, flexible tube through the cervix and into the uterus. ...

  8. THE EFFECT OF IRISQUINONE ON THE GLUTATHIONE SYSTEM AND MRP EXPRESSION OF CISPLATIN-RESISTANT HUMAN LUNG ADENOCARCINOMA CELL LINE (A549DDP)

    Institute of Scientific and Technical Information of China (English)

    LIANG; li

    2001-01-01

    [1] Li DH. A novel radiosensitizer "ANKA" for tumor (Irisquinone) [J]. Chin J Clin Oncol 1999; 26:153.[2]Bordow SB, Haber M, Madafiglio J, et al. Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma [J]. Cancer Res 1994; 54:5036.[3]Cai P, Liu XY, Han FS, et al. Establishment human lung adenocarcinoma cisplatin-resistant cell line A549DDP and the mechanism of its drug resistance [J]. Chin J Clin Oncol 1995; 22:582.[4]Cai P, Liu XY, Wang P. The value of glutathione reductase recycling assay measurement of content of glutathione in human plasma during tumor chemotherapy [J]. Chin J Clin Oncol l994; 21:717.[5]Zhan MC, Liu XY, Cai P, et al. Mechanism of resistance of human cell line A549DDP to cisplatin [J]. Chin J Clin Oncol 1998; 25:726.[6]Wang J, Liu XY, Wu MN, et al. Expression and reversion of drug resistance- and apoptosis- related genes of a DDP-resistant lung adeno-carcinoma cell line A549DDP [J]. Chin J Oncol 1999; 21:422.[7]Ishikawa T. The ATP-dependent glutathione S-conjugate export pump [J]. Treads Biol Sci 1992; 17:463.[8]Goto S, Yoshida K, Morikawa T, et al. Augmen-tation of transport for cisplatin-glutathione adduct in cisplatin-resistant cancer cells [J]. Cancer Res 1995; 55:4297.[9]Fujil R, Mutoh M, Sumizama T, et al. Adenosine triphosphate-dependent transport of leukotriene C4 by membrane vesicles prepared from cis-platinum-resistant human epidermoid carcinoma tumor cells [J]. JNCI 1994; 86:1781.[10]Ishikawa T, Ali-Osman F. Glutathion-associated cis-diamminedichloroplatinum (II) metabolism and ATP-dependent efflux from leukemia cells [J]. J Biol Chem 1993; 268:20116.[11]Ishikawa T, Wrighe CE, Ishizuka H. GS-X pumq is function ally overexpressed in cis-diammine-dichloroplatinum (II)-resistant human leukemia HL-60 cells and downregulated by cell differentiation [J]. J Biol Chem 1994; 269: 29085.

  9. The effects of PGC-1α on the proliferation and energy metabolism of malignant endometrial cancer cells

    Directory of Open Access Journals (Sweden)

    Ren Z

    2015-04-01

    Full Text Available Zhongqian Ren, Hui Yang, Cuicui Wang, Xiaoxin MaDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaBackground: It is well known that peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α plays an important role in tissue energy metabolism. However, the roles of PGC-1α in malignant endometrial cancer remain unknown.Methods: Forty cases of endometrial carcinoma, 15 cases with proliferative endometrial tissues, and 21 cases with normal endometrial tissues were collected. Real-time polymerase chain reaction was used to detect the mRNA levels of PGC-1α and estrogen-related receptor gamma (ERRγ. ELISA (enzyme-linked immunosorbent assay was used to detect the concentrations of pyruvate kinase and isocitrate dehydrogenase. The results were analyzed using medical statistical methods.Results: The mRNA levels of PGC-1α and ERRγ in the endometrial carcinoma tissues and hyperplasic endometrial tissues were significantly greater than those in the normal endometria. The mRNA levels of PGC-1α and ERRγ in the endometrial carcinoma patients with type 2 diabetes were higher than those in patients without diabetes. The mRNA levels of PGC-1α and ERRγ in the endometrial adenocarcinomas increased with clinical staging, depth of myometrial invasion, and increases in the number of metastatic lymph nodes. The PGC-1α mRNA level was positively correlated with ERRγ in the endometrial carcinoma tissues. The mRNA levels of PGC-1α were positively correlated with the concentrations of pyruvate kinase and isocitrate dehydrogenase in the endometrial carcinoma tissues, and similar results were found for ERRγ.Conclusion: Our results suggested that the upregulation of PGC-1α and ERRγ in endometrial cancer might be a requirement for cancer cell energy metabolism, which contributes to the development of endometrial cancer.Keywords: endometrial cancer, peroxisome

  10. [Effects of paclitaxel and gefitinib on the proliferation and cell cycle of human lung adenocarcinoma cell SPC-A1.].

    Science.gov (United States)

    Jia, Gang; Zhang, Weimin; Zhou, Juan; Zhu, Zhixia

    2008-06-20

    Previous clinical trials showed that there was no clinical benefit in the treatment of advanced non-small cell lung cancer when chemotherapy combined with gefitinib. The present study aims to assess the sequential administration of paclitaxel and gefitinib on the cell proliferation of lung adenocarcinoma cell SPC-A1 and to explore its mechanism by observing their effects on the cell cycle. The expression of EGFR mRNA and EGFR protein were examined by RT-PCR and western blotting respectively. MTT was used to measure the cell proliferation of SPC-A1 cells. Cell cycle was detected by flow cytometry. Both EGFR mRNA and EGFR protein were overexpressed in SPC-A1 cells. From 1*10(-14) M to 1*10(-6) M, both paclitaxel and gefitinib inhibited the cell proliferation of SPC-A1 cells in a dose-dependent and time-dependent manner in vitro . The effects of paclitaxel in combination with gefitinib on cell proliferation depended on the sequence. No significant additive effects on cell proliferation was found when they were used simultaneously or gefitinib was added before paclitaxel. However, sequential administration of gefitinib following paclitaxel can remarkably enhanced the effect of paclitaxel on the cell proliferation of SPC-A1 cells. Cell cycle studies showed that paclitaxel and gefitinib induced G2/M and G0/G1 arrest respectively. The G0/G1 arrest was observed when paclitaxel and gefitinib was used simultaneously or gefitinib was added before paclitaxel. In contrast, sequential administration of gefitinib following paclitaxel induced G2/M arrest. Both paclitaxel and gefitinib inhibits the cell proliferation of SPC-A1 cells. The additive effects on cell proliferation are sequential-dependent. The concomitant and the sequential treatment of gefitinib followed by paclitaxel exert no significant additive effects on the cell proliferation and resulted in the accumulation of cells in G0/G1 phase, which may decrease the effectiveness of paclitaxel in subsequent cycles. The

  11. Correlation of the expression of gonadotropin releasing hormone and its receptor in human gastric adenocarcinoma cell proliferation and differentiation%GnRH及其受体的表达与胃腺癌细胞增殖和分化的相关性研究

    Institute of Scientific and Technical Information of China (English)

    孙绪德; 柴伟; 高昌俊; 张贵和; 陈蕾; 黄威权

    2003-01-01

    AIM:To investigate the possible correlation of the expression of gonadotropin releasing hormone(GnRH) and its receptor with of proliferating cell nuclear antigen(PCNA) in human gastric adenocarcinoma cell proliferation and differentiation.METHODS:GnRH and its receptor and PCNA were detected in 30 gastric adenocarcinoma by immunohistochemical ABC technique. RESULTS:GnRH and its receptor had the same distribution pattern in gastric adenocarcinoma cells.The positive signal was found mainly in cytoplasm.The content of GnRH and its receptor immunoreative product in high differentiatied adenocarcinoma was significantly higher than those of the other two groups and the low differentiatied adenocarcinoma was the lowest(P< 0.05).PCNA positive signal which was found mainly in nucleus was gradually abated along with the raising of the extent of the differentiation.The differences were significant among the three groups(P< 0.05). In human gastric adenocarcinoma,the expression of GnRH and its receptor was negative correlation with the expression of PCNA(r=0.9).CONCLUSION:GnRH might be involved in the regulation of human gastric adenocarcinoma cell proliferation and differentiation.

  12. The prevalence of endometrial hyperplasia and endometrial cancer in women with polycystic ovary syndrome or hyperandrogenism

    DEFF Research Database (Denmark)

    Holm, Nina Sofie Lillegaard; Glintborg, Dorte; Andersen, Marianne Skovsager

    2012-01-01

    Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of wome...

  13. Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer

    Directory of Open Access Journals (Sweden)

    Lorena Draghini

    2017-04-01

    Full Text Available Purpose : To report our experience on high-dose-rate brachytherapy (HDR-BT in patients with stage I-III endometrial cancer unfit to surgery. Material and methods : Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95, median Karnofsky performance status 90% (range, 60-100. Histology was endometrial adenocarcinoma in 14 (82%, and non-endometrial in 3 (18% patients. In 15 (88% patients, clinical stage was I and in remaining 2 (12% was III. All patients were evaluated with computed tomography (CT and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. Results : Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131, 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adeno­carcinoma LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma was 100% at 1 and 6 years (p = 0.05. Two (12% patients had G2 acute toxicity and two others (12% G1 late toxicity. Conclusions : Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection, it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology.

  14. Value of T cell receptor gamma alternate reading frame protein and keratin 5 in endometrial carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHAO Li-jun; LI Xiao-ping; QI Wen-juan; WANG Jian-liu; WEI Li-hui

    2013-01-01

    Background Tumors with different gene expression develop and progress in different ways.To deepen our understanding of the progression in endometrial cancer,and provide a useful tool for accurate diagnosis and prognosis assessment,we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of e