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  1. Article ; Online: Antiangiogenesis therapy for breast cancer: an update and perspectives from clinical trials.

    Fakhrejahani, Elham / Toi, Masakazu

    Japanese journal of clinical oncology

    2014  Volume 44, Issue 3, Page(s) 197–207

    Abstract: The development of new blood vessels is a crucial step in breast cancer growth, progression and dissemination, making it a promising therapeutic target. Breast cancer has a heterogeneous nature and the diversity of responsible angiogenic pathways between ...

    Abstract The development of new blood vessels is a crucial step in breast cancer growth, progression and dissemination, making it a promising therapeutic target. Breast cancer has a heterogeneous nature and the diversity of responsible angiogenic pathways between different tumors has been studied for many years. Inhibiting different targets in these pathways has been under investigation in preclinical and clinical studies for more than decades, among which antibody against vascular endothelial growth factor is the most studied. However, the clinical impact from antiangiogenic treatment alone or in combination with standard chemotherapeutic regimens has been relatively small till today. In this review, we summarize the most clinically relevant data from breast cancer treatment clinical trials and discuss safety and efficacy of common antiangiogenic therapies as well as biological predictive markers.
    MeSH term(s) Administration, Metronomic ; Angiogenesis Inhibitors/administration & dosage ; Angiogenesis Inhibitors/adverse effects ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Clinical Trials as Topic ; Female ; Humans ; Predictive Value of Tests ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Angiogenesis Inhibitors ; Antibodies, Monoclonal, Humanized ; Biomarkers, Tumor ; Protein Kinase Inhibitors ; Vascular Endothelial Growth Factor A ; Bevacizumab (2S9ZZM9Q9V) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1)
    Language English
    Publishing date 2014-01-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 190978-2
    ISSN 1465-3621 ; 0368-2811
    ISSN (online) 1465-3621
    ISSN 0368-2811
    DOI 10.1093/jjco/hyt201
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    Zs.A 1298: Show issues Location:
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  2. Article ; Online: Tumor angiogenesis: pericytes and maturation are not to be ignored.

    Fakhrejahani, Elham / Toi, Masakazu

    Journal of oncology

    2011  Volume 2012, Page(s) 261750

    Abstract: Angiogenesis, an essential component of tumor growth and survival, is regulated by complex interactions between several cell types and soluble mediators. Heterogeneous tumor vasculature originates from the collective effect of the nature of carcinoma and ...

    Abstract Angiogenesis, an essential component of tumor growth and survival, is regulated by complex interactions between several cell types and soluble mediators. Heterogeneous tumor vasculature originates from the collective effect of the nature of carcinoma and the complexity of the angiogenic network. Although the application of angiogenesis inhibitors in some types of cancers has shown clinical benefits, predictive markers to assess treatment effects have yet to be established. In this review, we focus on tumor vessel maturity as a potential marker for evaluating treatment response.
    Language English
    Publishing date 2011-10-09
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2461349-6
    ISSN 1687-8469 ; 1687-8450
    ISSN (online) 1687-8469
    ISSN 1687-8450
    DOI 10.1155/2012/261750
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  3. Article ; Online: Tumor Angiogenesis

    Elham Fakhrejahani / Masakazu Toi

    Journal of Oncology, Vol

    Pericytes and Maturation Are Not to Be Ignored

    2012  Volume 2012

    Keywords Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Tumor microvasculature characteristics studied by image analysis: histologically-driven angiogenic profile.

    Fakhrejahani, Elham / Asao, Yasufumi / Toi, Masakazu

    The International journal of biological markers

    2014  Volume 29, Issue 3, Page(s) e204–7

    Abstract: Angiogenesis, a hallmark of cancer, has been studied to be a potential marker for diagnosis, prognosis and therapy in breast cancer. To evaluate tumor angiogenesis, histological assessment has been a common approach and counting tumor microvessels after ... ...

    Abstract Angiogenesis, a hallmark of cancer, has been studied to be a potential marker for diagnosis, prognosis and therapy in breast cancer. To evaluate tumor angiogenesis, histological assessment has been a common approach and counting tumor microvessels after visualizing them by immunohistochemistry has been in use for a long time. With recent advances in digital pathology and image analysis, other characteristics of tumor vasculature can also be evaluated. In this article we briefly review the potentials of image analysis in assessing tumor microvessel morphologically that might be helpful in defining a better angiogenesis marker than other common markers like vessel count.
    MeSH term(s) Biomarkers, Tumor/analysis ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Immunohistochemistry ; Microvessels/metabolism ; Microvessels/pathology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/pathology ; Prognosis
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2014-09-30
    Publishing country Italy
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 645113-5
    ISSN 1724-6008 ; 0393-6155
    ISSN (online) 1724-6008
    ISSN 0393-6155
    DOI 10.5301/jbm.5000098
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    Zs.A 2491: Show issues Location:
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  5. Article: Correlation between thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level and in vitro chemosensitivity to 5-fluorouracil, in relation to differentiation in gastric cancer.

    Fakhrejahani, Elham / Miyamoto, Akiko / Tanigawa, Nobuhiko

    Cancer chemotherapy and pharmacology

    2007  Volume 60, Issue 3, Page(s) 437–446

    Abstract: Purpose: It has been suggested that the gene expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) help in the prediction of the response to 5-fluorouracil (5-FU) in vivo and in vitro in gastric cancers.: Methods: ... ...

    Abstract Purpose: It has been suggested that the gene expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) help in the prediction of the response to 5-fluorouracil (5-FU) in vivo and in vitro in gastric cancers.
    Methods: In this study, intratumoral TS and DPD gene expressions were evaluated with real time reverse transcriptional polymerase chain reaction technique to determine the correlation between the expression of these two genes and in vitro sensitivity to 5-FU, assessed by the histoculture drug response assay on 87 patients with gastric adenocarcinoma.
    Results: The sensitivity to 5-FU did not show any difference in clinicopathological groups. DPD gene level was higher in undifferentiated (n = 39) than differentiated (n = 48) tumors (P = 0.043). In differentiated tumors, TS gene expression levels were higher in the tumors with relative resistance to 5-FU, while in undifferentiated cases, DPD mRNA levels were higher in tumors that showed resistance to 5-FU in vitro (P = 0.043 and 0.007, respectively). DPD also had significant predictive value for 5-FU sensitivity in undifferentiated cases [R(S) = -0.401, P = 0.011]. TS and DPD gene expression levels were more highly correlated in undifferentiated compared to differentiated cases [R(S) = 0.515 and 0.359, respectively].
    Conclusions: Different gene expression might be responsible for 5-FU sensitivity in gastric cancers of different histologic origin.
    MeSH term(s) Adult ; Cell Differentiation/physiology ; Dihydrouracil Dehydrogenase (NADP)/genetics ; Female ; Fluorouracil/pharmacology ; Gene Expression Regulation, Enzymologic/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Middle Aged ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms/enzymology ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Stomach Neoplasms/surgery ; Thymidylate Synthase/genetics
    Chemical Substances RNA, Messenger ; Dihydrouracil Dehydrogenase (NADP) (EC 1.3.1.2) ; Thymidylate Synthase (EC 2.1.1.45) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2007-08
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-007-0448-1
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    Zs.A 1420: Show issues Location:
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  6. Article: Vascular branching point counts using photoacoustic imaging in the superficial layer of the breast: A potential biomarker for breast cancer.

    Yamaga, Iku / Kawaguchi-Sakita, Nobuko / Asao, Yasufumi / Matsumoto, Yoshiaki / Yoshikawa, Aya / Fukui, Toshifumi / Takada, Masahiro / Kataoka, Masako / Kawashima, Masahiro / Fakhrejahani, Elham / Kanao, Shotaro / Nakayama, Yoshie / Tokiwa, Mariko / Torii, Masae / Yagi, Takayuki / Sakurai, Takaki / Haga, Hironori / Togashi, Kaori / Shiina, Tsuyoshi /
    Toi, Masakazu

    Photoacoustics

    2018  Volume 11, Page(s) 6–13

    Abstract: This study aimed to identify the characteristics of the vascular network in the superficial subcutaneous layer of the breast and to analyze differences between breasts with cancer and contralateral unaffected breasts using vessel branching points (VBPs) ... ...

    Abstract This study aimed to identify the characteristics of the vascular network in the superficial subcutaneous layer of the breast and to analyze differences between breasts with cancer and contralateral unaffected breasts using vessel branching points (VBPs) detected by three-dimensional photoacoustic imaging with a hemispherical detector array. In 22 patients with unilateral breast cancer, the average VBP counts to a depth of 7 mm below the skin surface were significantly greater in breasts with cancer than in the contralateral unaffected breasts (p < 0.01). The ratio of the VBP count in the breasts with cancer to that in the contralateral breasts was significantly increased in patients with a high histologic grade (p = 0.03), those with estrogen receptor-negative disease (p < 0.01), and those with highly proliferative disease (p < 0.01). These preliminary findings indicate that a higher number of VBPs in the superficial subcutaneous layer of the breast might be a biomarker for primary breast cancer.
    Language English
    Publishing date 2018-06-20
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2716706-9
    ISSN 2213-5979
    ISSN 2213-5979
    DOI 10.1016/j.pacs.2018.06.002
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  7. Article ; Online: Clinical Report on the First Prototype of a Photoacoustic Tomography System with Dual Illumination for Breast Cancer Imaging.

    Fakhrejahani, Elham / Torii, Masae / Kitai, Toshiyuki / Kanao, Shotaro / Asao, Yasufumi / Hashizume, Yohei / Mikami, Yoshiki / Yamaga, Iku / Kataoka, Masako / Sugie, Tomoharu / Takada, Masahiro / Haga, Hironori / Togashi, Kaori / Shiina, Tsuyoshi / Toi, Masakazu

    PloS one

    2015  Volume 10, Issue 10, Page(s) e0139113

    Abstract: Photoacoustic tomography is a recently developed imaging modality that can provide high spatial-resolution images of hemoglobin distribution in tissues such as the breast. Because breast cancer is an angiogenesis-dependent type of malignancy, we ... ...

    Abstract Photoacoustic tomography is a recently developed imaging modality that can provide high spatial-resolution images of hemoglobin distribution in tissues such as the breast. Because breast cancer is an angiogenesis-dependent type of malignancy, we evaluated the clinical acceptability of breast tissue images produced using our first prototype photoacoustic mammography (PAM) system in patients with known cancer. Post-excisionally, histological sections of the tumors were stained immunohistochemically (IHC) for CD31 (an endothelial marker) and carbonic anhydrase IX (CAIX) (a marker of hypoxia). Whole-slide scanning and image analyses were used to evaluate the tumor microvessel distribution pattern and to calculate the total vascular perimeter (TVP)/area for each lesion. In this clinical study, 42 lesions were primarily scanned using PAM preoperatively, three of which were reported to be benign and were excluded from statistical analysis. Images were produced for 29 out of 39 cancers (visibility rate = 74.4%) at the median depth of 26.5 (3.25-51.2) mm. Age, menopausal status, body mass index, history of neoadjuvant treatment, clinical stage and histological tumor angiogenesis markers did not seem to affect the visibility. The oxygen saturation level in all of the measured lesions was lower than in the subcutaneous counterpart vessels (Wilcoxon test, p value<0.001), as well as in the counterpart contralateral normal breast region of interest (ROI) (Wilcoxon test, p value = 0.001). Although the oxygen saturation level was not statistically significant between CAIX-positive vs. -negative cases, lesional TVP/area showed a positive correlation with the oxygen saturation level only in the group that had received therapy before PAM. In conclusion, the vascular and oxygenation data obtained by PAM have great potential for identifying functional features of breast tumors.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/pathology ; Diagnostic Imaging ; Female ; Hemoglobins/chemistry ; Hemoglobins/metabolism ; Humans ; Mammary Neoplasms, Animal ; Mammography/methods ; Middle Aged ; Neovascularization, Pathologic/diagnostic imaging ; Neovascularization, Pathologic/pathology ; Photoacoustic Techniques ; Tomography, X-Ray Computed
    Chemical Substances Hemoglobins
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0139113
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  8. Article ; Online: Photoacoustic mammography capable of simultaneously acquiring photoacoustic and ultrasound images.

    Asao, Yasufumi / Hashizume, Yohei / Suita, Takahiro / Nagae, Ken-Ichi / Fukutani, Kazuhiko / Sudo, Yoshiaki / Matsushita, Toshikazu / Kobayashi, Shuichi / Tokiwa, Mariko / Yamaga, Iku / Fakhrejahani, Elham / Torii, Masae / Kawashima, Masahiro / Takada, Masahiro / Kanao, Shotaro / Kataoka, Masako / Shiina, Tsuyoshi / Toi, Masakazu

    Journal of biomedical optics

    2016  Volume 21, Issue 11, Page(s) 116009

    Abstract: We have constructed a prototype photoacoustic mammography system (PAM-02) capable of simultaneously acquiring photoacoustic (PA) and ultrasound (US) images. Each PA, US, and fused PA/US image can be acquired over a wide area of the breast using the ... ...

    Abstract We have constructed a prototype photoacoustic mammography system (PAM-02) capable of simultaneously acquiring photoacoustic (PA) and ultrasound (US) images. Each PA, US, and fused PA/US image can be acquired over a wide area of the breast using the scanning module of a US transducer, a PA detector, and optical prisms. The resolution of the PA images exhibits improvement from 2 to 1 mm compared to images acquired using our previous prototype. The maximum scan area of PAM-02 is 90 mm along the horizontal axis and 150 mm along the vertical axis. In a phantom experiment, the available depth was at least 45 mm. A representative example of the application of the PAM-02 prototype in clinical research at Kyoto University is presented and shows S-factor images, which are considered an approximation parameter related to hemoglobin saturation of tumor-related blood vessels. We confirmed the applicability of the system for anatomical and biological research.
    MeSH term(s) Adult ; Aged ; Algorithms ; Breast/diagnostic imaging ; Equipment Design ; Female ; Humans ; Image Processing, Computer-Assisted ; Mammography/methods ; Phantoms, Imaging ; Photoacoustic Techniques/methods ; Ultrasonography/methods
    Language English
    Publishing date 2016-11-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1309154-2
    ISSN 1560-2281 ; 1083-3668
    ISSN (online) 1560-2281
    ISSN 1083-3668
    DOI 10.1117/1.JBO.21.11.116009
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    Zs.A 4699: Show issues Location:
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  9. Article ; Online: Sinisan, a traditional Chinese medicine, attenuates experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats.

    Tang, Yu / Liao, Yonghui / Kawaguchi-Sakita, Nobuko / Raut, Vikram / Fakhrejahani, Elham / Qian, Niansong / Toi, Masakazu

    Journal of hepato-biliary-pancreatic sciences

    2011  Volume 18, Issue 4, Page(s) 551–558

    Abstract: Background/purpose: Sinisan, a traditional Chinese medicine, is effective for the treatment of gastrointestinal disorders. In this study, we investigated the potential protective role of Sinisan against chronic pancreatitis (CP) in rats.: Methods: CP ...

    Abstract Background/purpose: Sinisan, a traditional Chinese medicine, is effective for the treatment of gastrointestinal disorders. In this study, we investigated the potential protective role of Sinisan against chronic pancreatitis (CP) in rats.
    Methods: CP was induced in rats by intrapancreatic injection of trinitrobenzene sulfonic acid (TNBS). Rats were randomly divided into a sham group, a TNBS-induced CP group and a Sinisan-treated group. Serum amylase and histological score were used to evaluate the severity of disease. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-10 (IL-10) and α-smooth muscle actin (α-SMA) were also measured in the three groups. Mechanical allodynia was measured with von Frey filaments. In addition, the protein levels of nerve growth factor (NGF) were measured in pancreatic tissues.
    Results: Administration of Sinisan significantly decreased the severity of CP. In the Sinisan-treated group, serum amylase, TNF-α, IL-1β, COX-2 and α-SMA levels were lower and the level of IL-10 was upregulated compared with the TNBS-induced CP group. Furthermore, treatment with Sinisan significantly, though not completely, attenuated the allodynia. Simultaneously NGF expression was also significantly downregulated in the Sinisan-treated group compared with the TNBS-induced CP group.
    Conclusions: Sinisan could be an effective treatment modality for CP via its anti-inflammatory, anti-fibrotic and analgesic properties. It may be a promising drug candidate for the treatment of patients with CP.
    MeSH term(s) Actins/metabolism ; Animals ; Biomarkers/metabolism ; Blotting, Western ; Cyclooxygenase 2/metabolism ; Disease Models, Animal ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use ; Interleukin-10/metabolism ; Interleukin-1beta/metabolism ; Pancreas/drug effects ; Pancreas/metabolism ; Pancreas/pathology ; Pancreatitis, Chronic/chemically induced ; Pancreatitis, Chronic/drug therapy ; Pancreatitis, Chronic/metabolism ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Trinitrobenzenesulfonic Acid/toxicity ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Actins ; Biomarkers ; Drugs, Chinese Herbal ; Interleukin-1beta ; Tumor Necrosis Factor-alpha ; smooth muscle actin, rat ; Interleukin-10 (130068-27-8) ; Trinitrobenzenesulfonic Acid (8T3HQG2ZC4) ; Cyclooxygenase 2 (EC 1.14.99.1)
    Language English
    Publishing date 2011-07
    Publishing country Japan
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2536236-7
    ISSN 1868-6982 ; 1868-6974
    ISSN (online) 1868-6982
    ISSN 1868-6974
    DOI 10.1007/s00534-010-0368-z
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  10. Article: Clinical and histological significance of atypical glandular cell on Pap smear.

    Behtash, Nadereh / Nazari, Zeinab / Fakhrejahani, Farhad / Khafaf, Alireza / Azar, Elham Ghayouri

    The Australian & New Zealand journal of obstetrics & gynaecology

    2007  Volume 47, Issue 1, Page(s) 46–49

    Abstract: Background: Atypical glandular cell (AGC) on Pap smear is uncommon but may represent a variety of benign and malignant lesions.: Aim: The aim of this study was to evaluate the association between AGC on Pap smear and significant pathological finding ... ...

    Abstract Background: Atypical glandular cell (AGC) on Pap smear is uncommon but may represent a variety of benign and malignant lesions.
    Aim: The aim of this study was to evaluate the association between AGC on Pap smear and significant pathological finding to tailor management protocols.
    Methods: Between 2002 and 2005, 60 women with AGC on Pap smears were referred to our colposcopy clinic. Forty-one women underwent colposcopy-directed biopsy, endocervical curettage, endometrial sampling and cervical conisation to determine the cytological and histological correlations of AGC on Pap smears.
    Results: The mean age of the patients was 46.9 +/- 11.5 years (range, 23-80 years). Of these patients 13 patients (31.7%) were postmenopause and 28 patients (68.2%) were in reproductive age. We found eight (19.5%) significant pathological findings including four (9.7%) high-grade squamous intraepithelial lesion, one (2.4%) adenocarcinoma of uterus, one (2.4%) adenocarcinoma of cervix, one (2.4%) squamous cell carcinoma of cervix and one (2.4%) papillary serous tumour of ovary.
    Conclusion: AGC on Pap smear was associated with a clinically significant diagnosis in approximately 20% of our cases. The women with a diagnosis of AGC on cervicovaginal smear are needed to be evaluated at least with colposcopy, endocervical and endometrial curettage. Clinicians should be careful about the significance of AGC on Pap smears.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biopsy ; Cervix Uteri/pathology ; Colposcopy ; Conization ; Dilatation and Curettage ; Endometrium/pathology ; Female ; Humans ; Iran ; Middle Aged ; Papanicolaou Test ; Prospective Studies ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/pathology ; Vaginal Smears
    Language English
    Publishing date 2007-02
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 390815-x
    ISSN 1479-828X ; 0004-8666
    ISSN (online) 1479-828X
    ISSN 0004-8666
    DOI 10.1111/j.1479-828X.2006.00678.x
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