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Sample records for cervical carcinoma xenografts

  1. pO2 Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

    International Nuclear Information System (INIS)

    Ellingsen, Christine; Øvrebø, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit; Rofstad, Einar K.

    2012-01-01

    Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO 2 ) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO 2 fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO 2 was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO 2 fluctuations, the pO 2 fluctuation frequency in these regions, and the relative amplitude of the pO 2 fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO 2 in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO 2 and, thus, protect tumor tissue from cycling hypoxia.

  2. pO{sub 2} Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

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    Ellingsen, Christine; Ovrebo, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit [Radiation Biology and Tumor Physiology Group, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway); Rofstad, Einar K., E-mail: einar.k.rofstad@rr-research.no [Radiation Biology and Tumor Physiology Group, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway)

    2012-07-15

    Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO{sub 2}) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO{sub 2} fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO{sub 2} was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO{sub 2} fluctuations, the pO{sub 2} fluctuation frequency in these regions, and the relative amplitude of the pO{sub 2} fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO{sub 2} in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO{sub 2} and, thus, protect tumor tissue from cycling hypoxia.

  3. Assessment of Hypoxia in Human Cervical Carcinoma Xenografts by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Ellingsen, Christine; Egeland, Tormod A.M.; Gulliksrud, Kristine M.Sc.; Gaustad, Jon-Vidar; Mathiesen, Berit; Rofstad, Einar K.

    2009-01-01

    Purpose: Patients with advanced cervical cancer and highly hypoxic primary tumors show increased frequency of locoregional treatment failure and poor disease-free and overall survival rates. The potential usefulness of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing tumor hypoxia noninvasively was investigated in the present preclinical study. Methods and Materials: CK-160 and TS-415 human cervical carcinoma xenografts transplanted intramuscularly (i.m.) or subcutaneously (s.c.) in BALB/c nu/nu mice were subjected to DCE-MRI and measurement of fraction of radiobiologically hypoxic cells. Tumor images of K trans (the volume transfer constant of Gd-DTPA) and v e (the extracellular volume fraction of the imaged tissue) were produced by pharmacokinetic analysis of the DCE-MRI data. Fraction of radiobiologically hypoxic cells was measured by using the paired survival curve method. Results: Fraction of radiobiologically hypoxic cells differed significantly among the four tumor groups. The mean values ± SE were determined to be 44% ± 7% (i.m. CK-160), 77% ± 10% (s.c. CK-160), 23% ± 5% (i.m. TS-415), and 52% ± 6% (s.c. TS-415). The four tumor groups differed significantly also in K trans , and there was an unambiguous inverse relationship between K trans and fraction of radiobiologically hypoxic cells. On the other hand, significant differences among the groups in v e could not be detected. Conclusions: The study supports the clinical development of DCE-MRI as a method for assessing the extent of hypoxia in carcinoma of the cervix

  4. Connective tissue of cervical carcinoma xenografts: associations with tumor hypoxia and interstitial fluid pressure and its assessment by DCE-MRI and DW-MRI.

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    Hompland, Tord; Ellingsen, Christine; Galappathi, Kanthi; Rofstad, Einar K

    2014-01-01

    Abstract Background. A high fraction of stroma in malignant tissues is associated with tumor progression, metastasis, and poor prognosis. Possible correlations between the stromal and physiologic microenvironments of tumors and the potential of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in quantification of the stromal microenvironment were investigated in this study. Material and methods. CK-160 cervical carcinoma xenografts were used as preclinical tumor model. A total of 43 tumors were included in the study, and of these tumors, 17 were used to search for correlations between the stromal and physiologic microenvironments, 11 were subjected to DCE-MRI, and 15 were subjected to DW-MRI. DCE-MRI and DW-MRI were carried out at 1.5 T with a clinical MR scanner and a slotted tube resonator transceiver coil constructed for mice. Fraction of connective tissue (CTFCol) and fraction of hypoxic tissue (HFPim) were determined by immunohistochemistry. A Millar SPC 320 catheter was used to measure tumor interstitial fluid pressure (IFP). Results. CTFCol showed a positive correlation to IFP and an inverse correlation to HFPim. The apparent diffusion coefficient assessed by DW-MRI was inversely correlated to CTFCol, whereas no correlation was found between DCE-MRI-derived parameters and CTFCol. Conclusion. DW-MRI is a potentially useful method for characterizing the stromal microenvironment of tumors.

  5. Imaging of cervical carcinomas

    International Nuclear Information System (INIS)

    Soyer, P.; Michel, G.; Masselot, J.

    1990-01-01

    Recently, magnetic resonance imaging (MRI) and transrectal or transvaginal ultrasound (TRUS, TVUS) had an important place in imaging techniques of cervical carcinomas and raise the question of modifying the imaging strategies. For the diagnosis of primitive tumor, those techniques cannot take the place of clinical examination and gross examination. In the assessment of parametrial involvement, TRUS which has better accuracy than clinical examination, and MRI which is considered as the most accurate technique, have an important role to play. In the follow-up and the detection of recurrences, MRI is actually considered as the best imaging technique. The authors, according to recent data in literature and their own experience, present basic concepts of imaging strategies for staging and follow-up of cervical carcinomas [fr

  6. Cytology of treated cervical carcinoma

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    Shibata, Hideo

    1982-01-01

    The vaginal smear specimens of the patients who received operative therapy, irradiation or chemotherapy for cervical carcinoma were examined. Long-term follow-up vaginal cytology following treatment of cervical carcinoma is effective for the detection of local recurrence in an early stage. Serial cytology is also useful in evaluation of the effects of irradiation and chemotherapy for cervical carcinoma. Radiosensitive and prognostic significance of vaginal smears before and after radiation therapy was discussed. (author)

  7. Current Cervical Carcinoma Screening Guidelines

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    Megan J. Schlichte

    2015-05-01

    Full Text Available A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP and the American Society for Clinical Pathology (ASCP in 2012, and later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG. The 2012 recommendations underscore the utility of molecular testing as an adjunct to cytology screening for certain women and provide guidance to clinicians based on different risk-benefit considerations for different ages. This manuscript will review screening techniques and current recommendations for cervical cancer screening and human papilloma virus (HPV testing, as well as possible future screening strategies.

  8. Cryopreservation of human colorectal carcinomas prior to xenografting

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    Linnebacher, Michael; Maletzki, Claudia; Ostwald, Christiane; Klier, Ulrike; Krohn, Mathias; Klar, Ernst; Prall, Friedrich

    2010-01-01

    Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research

  9. Temporal morphologic changes in human colorectal carcinomas following xenografting.

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    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  10. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice

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    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-01-01

    AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W2) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm3; 30 mg/kg per day, 612 ± 46 mm3; 50 mg/kg per day, 563 ± 38 mm3; and 70 mg/kg per day, 221 ± 26 mm3. Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2

  11. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

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    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-09-28

    To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which

  12. Invasive cervical carcinoma (Stages IB-IIB)

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    Sironi, S.; Zanello, A.; Rodighiero, M.G.; Vanzulli, A.; Del Maschio, A.; Taccagni, G.L.; Belloni, C.

    1991-01-01

    In the patients with invasive cervical carcinoma, the accurate assessment of parametrial invasion greatly affects the therapeutic choice between surgery and radiation therapy. As a matter of fact, surgery is usually performed only in the patients with carcinoma confined to the cervix, whereas those with parametrial involvement, or more advanced stages, are treated with radiation therapy. This prospective study was aimed at investigating the comparative adequecy of CT and MR imaging in assessing parametrial status in the patients with invasive cervical cancer. Twenty-one consecutive patients, with histologic diagnosis of cervical carcinoma, were investigated. All of them were clinically considered as having invasive cervical cancer (FIGO stage IB-IIB) and subsequently underwent surgery. In all cases, detailed histology of the parametrium was obtained. Pathological data were compared with CT and MR findings in all cases. As for assessing parametrial involvement by cancer, CT had 62% accuracy, 63% sensitivity, and 60% specificity, versus MR imaging 81% accuracy, 69% sensitivity, and 80% specificify. Therefore, MR imaging appears to be superior to CT in assessing the parametrial status of patients with invasive cervical carcinoma; the method yields valuable information for treatment planning

  13. DCE-MRI of patient-derived xenograft models of uterine cervix carcinoma: associations with parameters of the tumor microenvironment

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    Anette Hauge

    2017-11-01

    Full Text Available Abstract Background Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contrast-enhanced (DCE MRI to assess the microvascular density (MVD, interstitial fluid pressure (IFP, and hypoxic fraction of patient-derived cervical cancer xenografts was investigated in the present study. Methods Four patient-derived xenograft (PDX models of squamous cell carcinoma of the uterine cervix (BK-12, ED-15, HL-16, and LA-19 were subjected to Gd-DOTA-based DCE-MRI using a 7.05 T preclinical scanner. Parametric images of the volume transfer constant (K trans and the fractional distribution volume (v e of the contrast agent were produced by pharmacokinetic analyses utilizing the standard Tofts model. Whole tumor median values of the DCE-MRI parameters were compared with MVD and the fraction of hypoxic tumor tissue, as determined histologically, and IFP, as measured with a Millar catheter. Results Both on the PDX model level and the single tumor level, a significant inverse correlation was found between K trans and hypoxic fraction. The extent of hypoxia was also associated with the fraction of voxels with unphysiological v e values (v e > 1.0. None of the DCE-MRI parameters were related to MVD or IFP. Conclusions DCE-MRI may provide valuable information on the hypoxic fraction of squamous cell carcinoma of the uterine cervix, and thereby facilitate individualized patient management.

  14. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  15. The effects of a picosecond pulsed electric field on angiogenesis in the cervical cancer xenograft models.

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    Wu, Limei; Yao, Chenguo; Xiong, Zhengai; Zhang, Ruizhe; Wang, Zhiliang; Wu, Yutong; Qin, Qin; Hua, Yuanyuan

    2016-04-01

    The application of picosecond pulsed electric field (psPEF) is a new biomedical engineering technique used in cancer therapy. However, its effects on cervical cancer angiogenesis are not clear. Therefore, the aim of the present study is to investigate the effects of psPEF on angiogenesis in cervical cancer xenograft models. Xenograft tumors were created by subcutaneously inoculating nude mice (athymic BALB/c nu/nu mice) with HeLa cells, then were placed closely between tweezer-type plate electrodes and subjected to psPEF with a gradually increased electric field intensity (0kV/cm, 50kV/cm, 60kV/cm, 70kV/cm). The direct effect on tumor tissue was observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). The changes of blood vessels and oxygen saturation (sO2) of tumors were monitored in vivo by photoacoustic tomography (PAT). The microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factors (HIF-1α and HIF-2α) were detected by immunohistochemical technique (IHC). Their protein expressions and gene transcription levels were evaluated using western blot (WB) and quantitative reverse transcription and polymerase chain reaction (RT-PCR). PsPEF induced obvious necrosis of cervical cancer tissue; with the increasing of electric field intensity, the MVD, vascular PA signal and sO2 values declined significantly. The protein expression and gene transcription levels of VEGF, HIF1α and HIF2α were significantly decreased at the same time. PsPEF exhibited dramatic anti-tumor and anti-angiogenesis effects in cervical cancer xenograft models by exerting direct effect on cancer cells and vascular endothelial cells and indirect effect on tumor angiogenesis-related factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Effects of curcumin on growth of human cervical cancer xenograft in nude mice and underlying mechanism

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    Aixue LIU

    Full Text Available Abstract The present study investigated the effects of curcumin (Cur on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control, 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05. The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05, and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05. Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.

  17. Sexual life after cervical carcinoma.

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    Buković, Damir; Strinić, Tomislav; Habek, Mario; Hojsak, Iva; Silovski, Hrvoje; Krhen, Ivo; Maloca, Ivana; Radan, Mirjana

    2003-06-01

    The aim of this study is to determine the differences in sexual life of women with cervical cancer after surgery and radiation therapy. A total of 210 patients treated for cervical cancer at the Department of Obstetrics and Gynecology, School of Medicine, University of Zagreb, Croatia between March 2001 and March 2003 were asked to fill in the questionnaire. Sexual life had worsened in 42.86% of the surgical patients, as had in 25.00% of irradiated patients (p 0.05)). More than 80% of patients didn't notice any changes in their partner's behavior. Almost every third woman felt certain change in her "body image", similar in both groups (p > 0.05). Need for consultations regarding sex life after diagnosis were recognized by 71.43% of patients. In conclusion we can say that considerable amount of attention should be given to psychological and sexual aspects of recovery of patients, because those aspects can significantly influence patients rehabilitation and prognosis.

  18. Radioimmunological diagnostics of endocrine disorders in radiotherapy of cervical carcinoma

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    Modnikov, O.P.

    1986-01-01

    In 117 patients with cervical carcinoma and 57 healthy women of the same age a radioimmunologic investigation of the systems hypophysis-adrenal glands and hypophysis-ovaries was carried out. Functional disorders in these systems were detected already before irradiation (hyperfunction of adrenal glands, diminished production of estradiol). The function of the systems hypophysis-adrenal glands and hypophysis-ovaries was diminished in patients with cervical carcinoma under radiotherapy. (author)

  19. Risk Factors Associated with Invasive Cervical Carcinoma among ...

    African Journals Online (AJOL)

    BACKGROUND: Cervical cancer is a more serious public health problem than other cancers in women in Sub-Saharan Africa in general and in Ethiopia in particular. Thus, this study assessed risk factors related to invasive cervical carcinomas in southwestern Ethiopia. METHODS: Unmatched case control study was ...

  20. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  1. Volumetrical and morphological responses of human laryngeal squamous cell carcinoma xenografts treated with fractionated irradiation

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    Hoogenhout, J.; Gasteren, H. van; Jerusalem, C.R.; Kal, H.B.

    1988-01-01

    Xenografts of both primary human laryngeal squamous cell carcinoma and its metastases were irradiated with five daily fractions of 5.0 Gy. Tumor volume changes, morphology, mitotic index and mitotic figures were studied. Primary xenografts disappeared within 17±3 days. Grafts of metastases showed complete regression within 26±5 days, or regrowth after a delay period. Mitotic activity was higher in the grafts of metastases. The number of mitotic figures decreased and ceased within 14 days in the primary tumor, while some were still occasionally noted in the grafts of metastases. Telophase stages were practically absent after the first fraction. This study suggests that the response of metastases to radiation therapy is lower than the response of the primary tumor. (orig.) [de

  2. Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling

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    Li, Hui; Jiao, Shun [Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou (China); Li, Xin [Department of Obstetrics and Gynaecology, RenMin Hospital of Wuhan University, Wuhan (China); Banu, Hasina; Hamal, Shreejana [Department of Clinical Medicine, Medical School of Yangtze University, Jingzhou (China); Wang, Xianrong, E-mail: Dr.XianRong.Wang@hotmail.com [Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou (China)

    2015-11-06

    Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers and has great potential therapeutic value. We show that tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell carcinoma through inhibiting Wnt/β-catenin signaling pathway. Tigecycline is effective in inducing apoptosis, inhibiting proliferation and anchorage-independent colony formation of Hela cells. The inhibitory effects of tigecycline are further enhanced upon combination with paclitaxel, a most commonly used chemotherapeutic drug for cervical cancer. In a cervical xenograft model, tigecycline inhibits tumor growth as a single agent and its combination with paclitaxel significantly inhibits more tumor growth throughout the duration of treatment. We further show that tigecycline decreases level of both cytoplasmic and nuclear β-catenin and suppressed Wnt/β-catenin-mediated transcription through increasing levels of Axin 1 in Hela cells. In addition, stabilization or overexpression of β-catenin using pharmacological and genetic approaches abolished the effects of tigecycline in inhibiting proliferation and inducing apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition to the treatment armamentarium for cervical cancer and targeting Wnt/β-catenin represents a potential therapeutic strategy in cervical cancer. - Highlights: • We repurposed the antibiotic drug tigecycline for cervical cancer treatment. • Tigecycline is effectively against cervical cancer cells in vitro and in vivo. • Combination of tigecycline and paclitaxel is synergistic in targeting Hela cells. • Tigecycline acts on Hela cells through inhibiting Wnt/β-catenin signaling.

  3. Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling

    International Nuclear Information System (INIS)

    Li, Hui; Jiao, Shun; Li, Xin; Banu, Hasina; Hamal, Shreejana; Wang, Xianrong

    2015-01-01

    Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers and has great potential therapeutic value. We show that tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell carcinoma through inhibiting Wnt/β-catenin signaling pathway. Tigecycline is effective in inducing apoptosis, inhibiting proliferation and anchorage-independent colony formation of Hela cells. The inhibitory effects of tigecycline are further enhanced upon combination with paclitaxel, a most commonly used chemotherapeutic drug for cervical cancer. In a cervical xenograft model, tigecycline inhibits tumor growth as a single agent and its combination with paclitaxel significantly inhibits more tumor growth throughout the duration of treatment. We further show that tigecycline decreases level of both cytoplasmic and nuclear β-catenin and suppressed Wnt/β-catenin-mediated transcription through increasing levels of Axin 1 in Hela cells. In addition, stabilization or overexpression of β-catenin using pharmacological and genetic approaches abolished the effects of tigecycline in inhibiting proliferation and inducing apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition to the treatment armamentarium for cervical cancer and targeting Wnt/β-catenin represents a potential therapeutic strategy in cervical cancer. - Highlights: • We repurposed the antibiotic drug tigecycline for cervical cancer treatment. • Tigecycline is effectively against cervical cancer cells in vitro and in vivo. • Combination of tigecycline and paclitaxel is synergistic in targeting Hela cells. • Tigecycline acts on Hela cells through inhibiting Wnt/β-catenin signaling.

  4. Biological characterization of two xenografts derived from human CUPs (carcinomas of unknown primary

    Directory of Open Access Journals (Sweden)

    Bernheim Alain

    2007-12-01

    Full Text Available Abstract Background Carcinomas of unknown primary site (CUP are epithelial malignancies revealed by metastatic lesions in the absence of any detectable primary tumor. Although they often adopt an aggressive clinical pattern, their basic biology remains poorly understood. Laboratory research on their biology have been hampered so far by the absence of cell lines representative of CUPs. Methods We attempted xenografts of CUP clinical specimens in immunodeficient mice and subsequent in vitro culture of transplanted malignant cells. Whenever possible, malignant xenografted or cultured cells were characterized by microsatellite genotyping, immunohistology, electron microscopy, multifish chromosome analysis and search of TP 53 gene mutations. Results Successful xenografts were achieved in 2 cases out of 4. One of them (Capi1 was lost after 3 passages whereas the other one (Capi3 has been adapted to in vitro culture and is currently available to the scientific community with reliable identification based on microsatellite genotyping. Both Capi1 and Capi3 have histological characteristics of adenocarcinomas and display intense expression of EMA, CEA and cytokeratin 7. Multifish chromosome analysis demonstrated a translocation involving chromosomes 4 and 21 in both specimens. Distinct rare missense mutations of the TP53 gene were detected in Capi1 (codon 312 and Capi3 (codon 181; the codon 181 mutation is consistent with a previously reported similar finding in a small series of CUP specimens. Finally, intense membrane expression of c-kit was recorded in Capi3. Conclusion Our data suggest that xenografted tumors can be obtained from a substantial fraction of CUP clinical specimens. The hypothesis of a preferential association of CUPs with TP 53 mutations of codon 181 deserves further investigations. The Capi3 cell line will be a useful tool for assessment of novel c-kit inhibitors.

  5. Spectral CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts: preliminary animal experience

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Shudong [Jiangsu University, Department of Radiology, The Affiliated Renmin Hospital, Zhenjiang, Jiangsu (China); Shanghai Jiao tong University, School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Huang, Wei; Song, Qi; Lin, Xiaozhu; Wang, Zhongmin; Chen, Kemin [Shanghai Jiao tong University, School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Chen, Yerong [Jiangsu University, Department of Radiology, The Affiliated Renmin Hospital, Zhenjiang, Jiangsu (China)

    2014-09-15

    We sought to evaluate the capability of spectral CT to detect the therapeutic response to {sup 125}I interstitial brachytherapy in a pancreatic carcinoma xenograft nude mouse model. Twenty mice bearing SWl990 human pancreatic cancer cell xenografts were randomly separated into two groups: experimental (n = 10; 1.0 mCi) and control (n = 10; 0 mCi). After a two-week treatment, spectral CT was performed. Contrast-to-noise ratio (CNR) and iodine concentration (IC) in the lesions were measured and normalized to the muscle tissue, and nIC CD31 immunohistochemistry was used to measure microvessel density (MVD). The relationships between the nIC and MVD of the tumours were analysed. The nIC of the experimental group was significantly lower than that of the control group during the multiphase examination. A significant difference in the MVD was observed between the two groups (P <0.001). The nIC values of the three-phase scans have a certain positive correlation with MVD (r = 0.57, p < 0.0001; r = 0.48, p = 0.002; r = 0.63, p = 0.0017 in the 10, 25, and 60 s phase, respectively). Spectral CT can be a useful non-invasive imaging modality in evaluating the therapeutic effect of {sup 125}I interstitial brachytherapy to a pancreatic carcinoma. (orig.)

  6. Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies

    DEFF Research Database (Denmark)

    Kjær, Susanne Krüger

    2009-01-01

    of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks......High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number...... for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend or =6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2...

  7. Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

    Science.gov (United States)

    Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

    2013-08-01

    Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

  8. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation.

    Science.gov (United States)

    Zhao, Carolyn Ying; Szekely, Laszlo; Bao, Wenjie; Selivanova, Galina

    2010-04-15

    Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6-dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6-mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6-mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. (c)2010 AACR.

  9. Case of radiation induced carcinoma of the cervical esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Iwase, K.; Miura, K.; Kawase, K.; Yamaguchi, A.; Kondo, S. (Fujita-Gakuen Univ., Nagoya (Japan). School of Medicine)

    1980-07-01

    A patient with carcinoma of the cervical esophagus who visited a hospital with a complaint of difficulty in swallowing was reported. This patient was a 50 year old woman. It was 32 years since she had had external irradiation with x- ray over the neck for Basedow's disease at the age of 18. From the age of 30, she had had hypothyroidism and had used thyroid. She became aware of difficulty in swallowing in October, 1976. Then this symptom progressed gradually, and she also had hoarseness. She visited a hospital in August, 1977. At the first medical examination, pigmentation and atrophic changes in the neck induced by radiation were observed, and some lymphnodes with the size of a red bean were palpated. Esophageal roentogenography revealed circular and spiral type lesion in the cervical esophagus, which was 4 cm in length and had a clear boundary. Endoscopic examination revealed circular stenotic lesion. This lesion was diagnosed as squamous cell carcinoma by biopsy. Total of 3,000 rad of Linac x-ray was irradiated over the neck and the clavicle before operation. Operation findings revealed fibrosis, atrophy, and hardening of the thyroid gland caused by radiation. Carcinoma with the size 35 mm x 18 mm was limited to the cervical esophagus, and the degree of the progress was A/sub 2/, N/sub 2/, M/sub 0/ (Pl/sub 0/). Histological findings revealed moderately differentiated squamous cell carcinoma and its metastases to the right supraclaviclar lymphnodes. This carcinoma was diagnosed as radiation-induced carcinoma of the cervical esophagus, because this patient had had irradiation over the neck, locally marked atrophic changes and scar remained, and carcinoma occurred in the area which had been irradiated with x-ray.

  10. Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

    DEFF Research Database (Denmark)

    Norling, Rikke; Buron, Birgitte Marie Due; Therkildsen, Marianne Hamilton

    2014-01-01

    INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US...

  11. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

    Directory of Open Access Journals (Sweden)

    Ping Zhao

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

  12. MR imaging for staging of cervical carcinoma: Update

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Seong Kuk; Kim, Dong Won [Dong A University Hospital, Busan(Korea, Republic of)

    2017-08-15

    Uterine cervical cancer is globally the third most common cancer among women, and shows high mortality with invasive cervical carcinoma. Early detection of the disease, its correct staging, and treatment are therefore of great importance. The staging system updated in 2009 by the International Federation of Gynecology and Obstetrics (FIGO), is commonly used for planning the treatment. However, there are significant inaccuracies in the FIGO staging system. Accurate tumor staging is very important to decide the treatment strategy. Although not included in the staging system, magnetic resonance (MR) imaging is a valuable tool for local staging of the disease, and is useful in assessing the spread of the tumor and metastatic lymph nodes, thereby becoming a more accurate substitute for clinical staging of cervical carcinoma. In addition, it is capable of assessing the disease response to surgery or chemoradiation. This review briefly describes the role of MR imaging and the basic MR scanning protocol in evaluating cervical carcinoma. The MR findings with staging, and MR evaluation of treatment response, are further addressed.

  13. Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

    Science.gov (United States)

    Sheehan, P F; Baker, T; Tutton, P J; Barkla, D H

    1996-01-01

    1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.

  14. Radioimaging of human mammary carcinoma xenografts in nude mice with a new monoclonal antibody

    International Nuclear Information System (INIS)

    Senekowitsch, R.; Bode, W.; Kriegel, H.; Reidel, G.; Pabst, H.W.

    1986-01-01

    A female Wistar rat aged 33 days was immunized by repeated intraperitoneal injections of a cell suspension of mammary carcinoma for eight months. Spleen cells of the immunized rat were then fused with X63-Ag8.653, a mouse myeloma line. Hybridoma supernatants were screened by ELISA using cells of mammary carcinoma (MaCa) as target cells. Initially 72 hybridomas showed positive response with MaCa cells, but no cross-reaction with normal mammary tissue was seen. Clone Ma 10-11 was chosen for its stable growth in vitro and in ascitic fluid. Monoclonal antibody obtained from ascitic fluid induced by intraperitoneal injection of 10 7 hybridoma cell into BALB/c-nu/nu mice was separated from albumin and transferrin. After separation only one band positioned at 155000 MW on SDS-PAGE slabs was detected. Radiolabeling with 131 I was achieved with the Iodogen method, the efficiency of labeling was 88%. 1.85 MBq of the intact labeled rat antibody were injected into nude mice xenografted with human mammary carcinoma and scintigrams were obtained every 48 hours p.i. up to 15 days. Scintigraphic images permitted tumor detection at 3 days p.i., but good tumor localization needed 8 days p.i.. The tumor-to-blood ratios calculated after dissection of tumor-bearing mice in groups of 3 increased from 0.97 at day 3 to 3 at day 15 p.i.. No uptake of the antibody in other organs was found. The half-life of the whole body clearance of the rat immunoglobulin was 36 h. This is significantly shorter than the half-life found for mouse immunoglobulin in nude mice. (Author)

  15. Intestinal damage and malabsorption after treatment for cervical carcinoma

    International Nuclear Information System (INIS)

    Lantz, B.

    1984-01-01

    Sixty-two patients with cervical carcinoma were treated in 1966 to 1968. Thirty-two patients who were alive in 1982 were reevaluated concerning intestinal function. An initial low folate value associated with the disease did not correlate with prognosis. A late low folate value indicated malabsorption and not recurrence of the carcinoma. Malabsorption was found in 5/23 patients (22%) and 3 of these (13%) had vitamin B 12 deficiency. Intestinal damage in tumour free patients occurred in 2/62 (3%) patients. It is suggested that late silent complications such as malabsorption should be looked for in the preventive care of these patients. (Auth.)

  16. Establishment and characterization of 7 novel hepatocellular carcinoma cell lines from patient-derived tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Hong Xin

    Full Text Available Hepatocellular carcinoma (HCC is a common cancer with poor prognosis worldwide and the molecular mechanism is not well understood. This study aimed to establish a collection of human HCC cell lines from patient-derived xenograft (PDX models. From the 20 surgical HCC sample collections, 7 tumors were successfully developed in immunodeficient mice and further established 7 novel HCC cell lines (LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, LIXC012 and CPL0903 by primary culture. The characterization of cell lines was defined by morphology, growth kinetics, cell cycle, chromosome analysis, short tandem repeat (STR analysis, molecular profile, and tumorigenicity. Additionally, response to clinical chemotherapeutics was validated both in vitro and in vivo. STR analysis indicated that all cell lines were unique cells different from known cell lines and free of contamination by bacteria or mycoplasma. The other findings were quite heterogeneous between individual lines. Chromosome aberration could be found in all cell lines. Alpha-fetoprotein was overexpressed only in 3 out of 7 cell lines. 4 cell lines expressed high level of vimentin. Ki67 was strongly stained in all cell lines. mRNA level of retinoic acid induced protein 3 (RAI3 was decreased in all cell lines. The 7 novel cell lines showed variable sensitivity to 8 tested compounds. LIXC011 and CPL0903 possessed multiple drug resistance property. Sorafenib inhibited xenograft tumor growth of LIXC006, but not of LIXC012. Our results indicated that the 7 novel cell lines with low passage maintaining their clinical and pathological characters could be good tools for further exploring the molecular mechanism of HCC and anti-cancer drug screening.

  17. Investigation of cervical lymph node metastasis from primary unknown carcinoma

    International Nuclear Information System (INIS)

    Sagawa, Kosuke; Terada, Tomonori; Saeki, Nobuo; Uwa, Nobuhiro; Mohri, Takeshi; Sakagami, Masafumi

    2012-01-01

    We retrospectively evaluated 41 patients with metastatic cervical tumors from unknown primary sites at the Hyogo College of Medicine between 1997 and 2007. The N stage classification of cervical lymph nodes was: N1 in 3 cases, N2a in 10 cases, N2b in 10 cases, N2c in 4 cases, and N3 in 14 cases. The histopathological diagnoses of cervical lymph node were: squamous cell carcinoma in 33 cases, adenocarcinoma in 5 cases, undifferentiated carcinoma in 2 cases, and papillary carcinoma in 1 cases. Primary tumor sites were: tonsil in 5 cases, esophaguses in 2 cases, hypopharynxies in 2 cases, and thyroid, oral floor, submandibular gland, lung, gastric and colon in 1 case each. The useful tests were gastric endoscope, positron emission tomography-computed tomography (PET-CT), and blind biopsy of tonsil. We treated 24 of the 41 patients. Therapies were: neck dissection with postoperative radiation therapy in 11 cases, neck dissection alone in 1 case, only radiation or chemoradiation therapy alone in 8 cases, and chemotherapy alone in 4 cases. The 5-year survival rate was 40.1% in all cases and 81.5% in cases who underwent neck dissection. (author)

  18. The utilization of SA-gal in pre-targeting RIT of colon carcinoma xenograft models

    International Nuclear Information System (INIS)

    Wu Hubing; Huang Zuhan; Peng Wuhe; Gao Xiao

    2001-01-01

    To investigate the improved clearance effect of avidin (Av) and streptavidin-gal (SA - gal) for blood radiolabeled biotinylated antibody in pre-targeting radio-immuno therapy (RIT) of colon carcinoma xenograft models. Biotinylated antibody radiolabeled with 131 I was injected into the nude mice bearing the colon carcinoma via the tail vein. 24 h later, in 2 test groups, SA-gal or Av at a 10 - fold molar excess of antibody was intraperitoneally injected into the animals whereas no any chase agents were given to the control animals. Animals were killed for biodistribution study at 30h after 131 I-labelled biotinylated antibody administration. Results showed that Av and SA-gal took the effect of chase very fast. At 6h after injection, the blood level of radioactivity decreased very fast. The tumor/blood ratios of control group, Av chase group, SA-gal chase group were 0.42, 2.09, 5.23 respectively, P < 0.05 and P < 0.01 for the latter two groups as compared other control groups. Compared with Av, SA-gal showed better chase effect, its T/B ratios was 5.23, significantly higher than 2.09 of Av (P < 0.01). In the tissue biodistributions, relatively high non-specific radioactivity uptakes in non-liver organs were seen in Av chase group. Utilized in pre-targeting RIT, both Av and SA-gal could make the blood level of radioactivity decrease quickly and considerably improves tumor T/NT ratios. The chase effect of SA-gal was superior to that of avidin

  19. Cervical lymphadenopathy in childhood: nasopharyngeal carcinoma as a challenging diagnosis

    Directory of Open Access Journals (Sweden)

    Paula Martinez Vianna

    2012-12-01

    Full Text Available Nasopharyngeal carcinoma (NPC is a carcinoma that arises from the nasopharyngeal mucosa and differs from other head and neck carcinomas by its unique histologic, epidemiologic, and biologic characteristics. NPC is rare in most countries, especially Europe and North America. However, it has a high incidence in several regions of South China. The incidence variability of NPC, among different geographical and ethnic groups, indicates a combination of genetic susceptibility, infection by Epstein-Barr virus and environmental factors. NPC is classified into three histological subtypes according to the 1991 World Health Organization classification: squamous cell carcinoma, nonkeratinizing carcinoma, and basaloid squamous cell carcinoma. The symptoms of patients with NPC are related to the primary tumor site and the degree of dissemination. Therefore, patients can remain asymptomatic during a long period of time. Imaging exams and biopsy of the tumor mass generally are sufficient to establish the diagnosis. NPC is a rare disease among children. The authors report a case of a 12-year-old boy who sought medical attention complaining of a progressive growing tumoral mass on the right side of the neck. The computed tomography images of the head and neck and the histological examination of a cervical lymph node biopsy diagnosed a metastatic NPC.

  20. Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts

    International Nuclear Information System (INIS)

    Wessels, B.W.; Vessella, R.L.; Palme, D.F. II; Berkopec, J.M.; Smith, G.K.; Bradley, E.W.

    1989-01-01

    Growth delay was measured in TK-82 renal cell carcinoma (RCC) xenografts implanted in nude mice receiving single fraction external beam irradiation (SF-XRT), multifraction external beam irradiation (MF-XRT), or radioimmunotherapy (RIT). Thermoluminescent dosimeter(s) (TLD) and autoradiography were used to ascertain the average absorbed dose delivered and the degree of heterogeneous uptake of radiolabeled antibody for the RIT irradiations. For intravenous administered activities of 100, 200, 400, and 600 microCi of I-131 labeled A6H antibody, volume doubling times (VDT) and TLD absorbed dose measurements for each administered activity were 7 days (341 cGy), 38 days (383 cGy), 85 days (886 cGy) and no regrowth (1034 cGy), respectively. For SF-XRT irradiations of 500, 1000, and 1500 cGy, VDT times were 11, 62, and 103 days, respectively. MF-XRT of 4 X 250 cGy over a 2-week period yielded a VDT of 25 days. Marked peripheral activity deposition was noted on most autoradiographs from multiple tumor samples. These data suggest that an equivalent to superior tumor growth delay is obtained for absorbed doses delivered by exponentially decaying low dose rate radioimmunotherapy RIT compared to similar doses of acute dose rate XRT as quantitated by the TLD method

  1. Cytofluorophotometrical study of the DNA content of the uterine cervical carcinoma and the vaginal epithelium

    International Nuclear Information System (INIS)

    Tokumoto, Yoshiaki

    1987-01-01

    The Feulgen DNA content in cells of uterine cervical carcinoma and that of its adjacent vaginal epithelium were measured by microfluorophotometry. The Feulgen DNA content in cells of uterine cervical carcinoma was increased and showed a greater variation of its DNA values compared with diploid cells. The Feulgen DNA content in cells of normal vaginal epithelium adjacent to cervical carcinoma was also increased compared with diploid cells in 6 out of 8 cases. The relativity between the cellular DNA content of cervical carcinoma and that of its adjacent normal vaginal epithelium was found. In 10 out of 14 cases of uterine cervical carcinoma, the mean value of cellular DNA content was increased after by therapuetic irradiation with 10 Gy. Radiation effects on the DNA content of vaginal epithelial cells were similar to those on the DNA content of carcinoma cells. (author)

  2. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Ketao Jin

    Full Text Available The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

  3. A case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome.

    Science.gov (United States)

    Chen, Y; Zhang, Y; Wang, L; Yang, X

    2017-01-01

    To date, cervical carcinoma complicated with Cushing's syndrome were all diagnosed as small cell carcinoma histo- logically, but not adenosquamous carcinoma. Here the authors present the diagnosis, management, and prognosis of a case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome. A 28-year-old woman was admitted with the chief complaint of post-coital bleeding for one month. Gynecological examination revealed a nodular yellowish-pigmented vegetation (6x5 cm) on the cervix. Laboratory findings proved the diagnosis of Cushing's syndrome. Histopathological diagnosis showed the adenosquamous carcinoma with melanoma differentiation. Immunohistochemical stainings for melanoma A and anti- adrenocorticotropic hormone (ACTH) were positive in the majority of the tumor cells, which indicated that this melanocytic cervical carcinoma lesion was the source of ectopic ACTH production resulting in Cushing's syndrome. This is a unique case of a rare type of cervical carcinoma.

  4. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  5. Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Zhou, Yan; Chen, Yue [Department of Medical Imaging, Luzhou Medical College, Luzhou (China); Yang, LingLin, E-mail: yanglinglin2003@tom.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, JingBo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    2013-10-01

    Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

  6. Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang; Zhou, Yan; Chen, Yue; Yang, LingLin; Wu, JingBo

    2013-01-01

    Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I

  7. Endogenous sex steroids and risk of cervical carcinoma: results from the EPIC study

    DEFF Research Database (Denmark)

    Rinaldi, Sabina; Plummer, Martyn; Biessy, Carine

    2011-01-01

    Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC).......Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC)....

  8. Treatment results of radiotherapy for carcinoma of the cervical esophagus

    International Nuclear Information System (INIS)

    Yamada, Kazunari; Okuno, Yoshishige; Nakajima, Toshifumi; Kusumi, Fusako; Takakuwa, Hiroshi; Matsusue, Satoru; Murakami, Masao; Okamoto, Yoshiaki

    2006-01-01

    The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p<0.01) and tumor length (p<0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer

  9. Complications after radiation therapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Saitoh, Masataka

    1981-01-01

    From 1966 to 1973, 215 patients with cervical cancer were treated at the Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University. The patients were divided into two groups. In the first group, 123 patients were treated by external radiation with Tele- 60 Co plus radium insertions (1966-1970). In the second group, 83 patients were treated with linear accelerator plus cesium insertions (1970-1973). The results on both of 5-year survival rate and appearance of radiation injuries were compared with two groups. There was no significant difference in the cure rate between those of groups. The incidence of pigmentation, edema and diarrhea (early complications) was higher and the diarrhea continued significantly longer in the second group. The incidence of rectal ulcer and rectostenosis (later complications) was significantly higher than former group. A study was made to lean the reason for the significant higher occurrence of rectal ulcer and rectostenosis. As a result, it was determined that later complication was more emphasized especially by ret dose given intracavitary radiation. In addition, it is thought that the dose rate, the dose volume and natural history such as the patients' age are also related to the severity of the complication. (J.P.N.)

  10. Complications after radiation therapy for cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, M. (Iwate Medical Coll., Morioka (Japan). School of Medicine)

    1981-04-01

    From 1966 to 1973, 215 patients with cervical cancer were treated at the Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University. The patients were divided into two groups. In the first group, 123 patients were treated by external radiation with Tele-/sup 60/Co plus radium insertions (1966-1970). In the second group, 83 patients were treated with linear accelerator plus cesium insertions (1970-1973). The results on both of 5-year survival rate and appearance of radiation injuries were compared with in the two groups. There was no significant difference in the cure rate between those groups. The incidence of pigmentation, edema and diarrhea (early complications) was higher and the diarrhea continued significantly longer in the second group. The incidence of rectal ulcer and rectostenosis (later complications) was significantly higher than former group. A study was made to learn the reason for the significantly higher occurrence of rectal ulcer and rectostenosis. As a result, it was determined that later complication was more emphasized especially by dose rate of intracavitary irradiation. In addition, it is thought that the dose rate, the dose volume and natural history such as the patients' age are also related to the severity of the complications.

  11. Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas.

    Science.gov (United States)

    Li, Junwei; Bonifati, Serena; Hristov, Georgi; Marttila, Tiina; Valmary-Degano, Séverine; Stanzel, Sven; Schnölzer, Martina; Mougin, Christiane; Aprahamian, Marc; Grekova, Svitlana P; Raykov, Zahari; Rommelaere, Jean; Marchini, Antonio

    2013-10-01

    The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour remission in all co-treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment against cervical and pancreatic ductal carcinomas. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  12. Potent efficacy signals from systemically administered oncolytic herpes simplex virus (HSV1716 in hepatocellular carcinoma xenograft models

    Directory of Open Access Journals (Sweden)

    Braidwood L

    2014-10-01

    Full Text Available Lynne Braidwood, Kirsty Learmonth, Alex Graham, Joe Conner Virttu Biologics Ltd, Department of Neurology, Southern General Hospital, Glasgow, UK Abstract: Oncolytic herpes simplex virus (HSV1716, lacking the neurovirulence factor ICP34.5, has highly selective replication competence for cancer cells and has been used in clinical studies of glioma, melanoma, head and neck squamous cell carcinoma, pediatric non-central nervous system solid tumors, and malignant pleural mesothelioma. To date, 88 patients have received HSV1716 and the virus is well tolerated, with selective replication in tumor cells and no spread to surrounding normal tissue. We assessed the potential value of HSV1716 in preclinical studies with two human hepatocellular carcinoma cell lines, HuH7 and HepG2-luc. HSV1716 displayed excellent replication kinetics in vitro in HepG2-luc cells, a cell line engineered to express luciferase, and virus-mediated cell killing correlated with loss of light emissions from the cells. In vivo, the HepG2-luc cells readily formed light-emitting xenografts that were easily visualized by an in vivo imaging system and efficiently eliminated by HSV1716 oncolysis after intratumoral injection. HSV1716 also demonstrated strong efficacy signals in subcutaneous HuH7 xenografts in nude mice after intravenous administration of virus. In the HuH7 model, the intravenously injected virus replicated prolifically immediately after efficient tumor localization, resulting in highly significant reductions in tumor growth and enhanced survival. Our preclinical results demonstrate excellent tumor uptake of HSV1716, with prolific replication and potent oncolysis. These observations warrant a clinical study of HSV1716 in hepatocellular carcinoma. Keywords: oncolytic herpes simplex virus, HSV1716, hepatocellular carcinoma, xenografts, efficacy 

  13. Molecular analysis of primary gastric cancer, corresponding xenografts, and 2 novel gastric carcinoma cell lines reveals novel alterations in gastric carcinogenesis

    NARCIS (Netherlands)

    Milne, Anya N. A.; Sitarz, Robert; Carvalho, Ralph; Polak, Mirjam M.; Ligtenberg, Madolijn; Pauwels, Patrick; Offerhaus, G. Johan A.; Weterman, Marian A. J.

    2007-01-01

    We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using

  14. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation

    International Nuclear Information System (INIS)

    Bayer, Christine; Kielow, Achim; Schilling, Daniela; Maftei, Constantin-Alin; Zips, Daniel; Yaromina, Ala; Baumann, Michael; Molls, Michael; Multhoff, Gabriele

    2012-01-01

    Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD 50 ). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasm of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.

  15. Development of radiolanthanide labeled porphyrin complexes as possible therapeutic agents in beast carcinoma xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Vahidfar, Nasim; Aghanejad, Ayuob; Beiki, Davood; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Faculty of Pharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Bahrami-Samani, Ali; Alirezapour, Behrooz; Erfani, Mostafa [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiopharmacy Research Group

    2014-10-01

    Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their behaviour in the human body, ability to complex various radionuclides, water solubility, low toxicity etc., in this work radio ytterbium/samarium porphyrin complexes have been developed. {sup 175}Yb and {sup 153}Sm labeled 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrins ([{sup 175}Yb]-TDMPP/[{sup 153}Sm]-TDMPP) were prepared using 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (H{sub 2}TDMPP) and [{sup 175}Yb]YbCl{sub 3} or [{sup 153}Sm]SmCl{sub 3} in 12-24 h at 60 C. Stability of the complexes were checked in final formulation and human serum for 24 h, followed by partition coefficient determination and biodistribution studies in wild type and breast carcinoma-bearing mice. The radiocomplexes were obtained with acceptable radiochemical purity (> 95% (paper chromatography) and > 96% (HPLC) for [{sup 175}Yb]-TDMPP and > 97% (paper chromatography) and > 98% (HPLC) for [{sup 153}Sm]-TDMPP) with specific activities of 12-15 GBq/mmol and 278 GBq/mmol at the end of bombardment for [{sup 175}Yb]-TDMPP and [{sup 153}Sm]-TDMPP respectively. The partition coefficients were determined for [{sup 175}Yb]-TDMPP and [{sup 153}Sm]-TDMPP (log P = 0.63 and log P = 0.96 respectively). The [{sup 175}Yb]-TDMPP complex is mostly washed out from the circulation through kidneys. Liver and spleen also demonstrated significant activity uptake in 72 h post injection. Also [{sup 153}Sm]-TDMPP, is mostly washed out from the circulation through kidneys, however lungs are the major accumulation sites. The [{sup 153}Sm]-TDMPP complex demonstrated significant targeted uptake in breast carcinoma xenografts with tumor: blood ratios of 10.67, 10.47 and 19.01 in 24, 48 and 72 h respectively. Also interesting tumor: kidney/liver ratios were obtained. {sup 153}Sm-TDMPP properties suggest an efficient tumor targeting agent with high tumor-avidity. Further investigation on the therapeutic properties must be

  16. Ovarian and cervical cancer patient derived xenografts: The past, present, and future.

    Science.gov (United States)

    Boone, Jonathan D; Dobbin, Zachary C; Straughn, J Michael; Buchsbaum, Donald J

    2015-08-01

    Preclinical research in gynecologic malignancies has largely relied upon cloned cancer-derived cell lines and tumor xenografts derived from these cell lines. Unfortunately, the use of cell lines for translational research has disadvantages because genetic and phenotypic alterations from serial passaging have resulted in expression profiles that are different from the original patient tumors. The patient-derived xenograft (PDX) model derived from human tumor not previously cultured has shown better representation of the heterogeneity of gynecologic malignancies and the human tumor microenvironment with preservation of cytogenetics, cellular complexity, and vascular and stromal tumor architecture. Studies have shown promise with these models to analyze tumor development and adaptation, test drug efficacy, and predict clinical outcomes. Their ultimate value may be seen with preclinical drug screening including novel targeted therapies, biomarker identification, and the development of individualized treatment plans. This article reviews PDX model development, current studies testing chemotherapeutics and targeted therapies, and limitations of the PDX model in gynecologic malignancies. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The CT evaluation of cephalic and cervical adenoid cystic carcinoma

    International Nuclear Information System (INIS)

    Gu Yajia; Wang Jiuhua; Wang HOngshi; Chen Tongzhen

    2000-01-01

    Objective: To evaluate the CT manifestations of cephalic and cervical adenoid cystic carcinoma (ACC). Methods: Thirty-three cases of ACC were analyzed retrospectively. Of all cases, 22 cases underwent operation and 11 cases received radiotherapy. The manifestations of CT were evaluated and compared with the clinical and pathologic results. Results: Tumors originated from parotid gland (5 cases), floor of mouth (5 cases), nasal cavity and nasopharynx (5 cases), tongue (4 cases), palate (3 cases), tracheas (3 cases), submandibular gland (2 cases), tonsilla (2 cases), maxillary sinus (2 cases), and cheek (2 cases), respectively. The CT manifestations included: (1)ethmoid density in 21 cases, partial ethmoid density in 5 cases. (2)the morphology of ACC was irregular and the growth of the tumor was amorphous in 17 cases, and the margin of the tumor was vague in 20 cases. (3)ACC often grew along the nerve with infiltration, which caused destruction of the skull base in 5 cases and atrophy of mastication muscles and/or buccinator in 3 cases. Conclusion: (1)The characteristics of cephalic and cervical adenoid cystic carcinoma on CT scans were ethmoid density, infiltrated growth, growing along the nerve with infiltration, and submucous growth. Among them, the most important manifestation, which could lead to the histologic diagnosis on CT, was ethmoid density. (2)The range of ACC was usually underestimated on CT. (3)The manifestation of tumor growth along the nerve could be apparently displayed on MRI

  18. Peculiarities of endotoxemia during radiotherapy of cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gabelov, A A; Kiselev, P N; Shul' s, T S [Tsentral' nyj Nauchno-Issledovatel' skij Rentgeno-Radiologicheskij Inst., Leningrad (USSR)

    1981-11-01

    Radiotherapy in cervical carcinoma patients is frequently followed by severe intestinal injuries which serve as prerequisites for the penetration of endotoxins of intestinal microflora into the systemic circulation. Peculiarities of possible development of endotoxemia were studied in 45 women with cervical carcinoma (Stages 2, 3). Radiotherapy was performed by routine methods (long-focus irradiation with subsequent intracavitary irradiation, or simultaneous long-focus and intracavitary irradiation). The presence of bacterial endotoxins in the patients blood was revealed by the testing of the lethal effect after intraperitoneal administration of the examined blood (0.1 ml) to random-bred albino mice simultaneously with actinomycin D(10 ..mu..g/mouse) that sharply increases the sensitivity of animals to a toxic effect of endotoxins. It has been established that involvement of the intestine in irradiation is followed by endotoxemia regardless of radiotherapeutic methods. The degree of severity of endotoxemia developing in the first half of a radiotherapeutic course depends on a radiation dose. On reaching a certain level, endotoxemia preserves its severity up to the end of irradiation and at early time after its completion.

  19. Study of bone metastasis of cervical carcinoma by bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, Shinsuke; Okamoto, Yoshiaki; Maeda, Takayoshi; Sano, Takashi; Ueki, Minoru; Sugimoto, Osamu; Sakata, Tsunehiko; Yamasaki, Kouichi; Akagi, Hiroaki

    1985-04-01

    In carrying out bone scintigraphy in 224 cases over the 5 years from June, 1978 to May, 1983 as a part of the post-treatment management of cervical carcinoma. Bone metastases were seen in 12.5% (28 cases) of the subjects, about 6% of the total post-treatment cases of cervical carcinoma in the corresponding period (466 cases). Bone metastases were seen in 9.3% (16/172) of post-operative cases, compared with 23.1% (12/52) of non-operative cases. Bone metastases were not seen in clinical stages Ia through IIa (49 cases) but were seen in IIb or higher stages. Bone metastasis rates by histological type, according to WHO classification, were 12.8% (26/203) in squamous cell carcinoma, 5.9% (1/17) in adenocarcinoma, and 25% (1/4) in adenosquamous carcinoma. Among the squamous cell carcinoma cases, small cell non-keratinizing type had the highest bone metastasis rate. Of 172 post-operative cases, 20.8% (11/53) of those with lymph node metastasis exhibited bone metastasis, higher than the 4.2% (5/119) in cases without lymph node metastasis. As to CPL classification, bone metastasis was seen more often in L type (18.8%) than C(0.0%) or P types (6.6%). Our risk classification of 168 cases demonstrated that bone metastasis was not seen in risk I group (74 cases), but was seen in 6.7% (1/17) of risk II group and in 19.0% (15/79) of risk III group. Twenty-eight cases with bone metastasis included 11 cases with local recurrence, 8 with pulmonary metastases, 4 with hepatic metastases and 4 with Virchow's lymphnode metastases. The 28 bone metastasis cases included 10 cases with multiple bone metastases and 5 with only a single bone metastasis. Most bone metastases were seen in the lumbar vertebrae and the pelvic bone. Post-operative cases had more distant metastases than non-operative cases. On diagnosis of bone metastases and 17 of the 28 patients had pain, 6 of the remaining 11 patients developing pain thereafter. (J.P.N.).

  20. Experimental radioimmunoimaging of human lung small cell carcinoma xenograft H-69 by NCC-ST-433 monoclonal antibody

    International Nuclear Information System (INIS)

    Kubota, Tetsuro; Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Watanabe, Masahiko; Ishibiki, Kyuya; Abe, Osahiko

    1989-01-01

    NCC-ST-433 monoclonal antibody raised against human gastric carcinoma xenograft (St-4) was labeled with l25 I using enzymatic and Iodogen methods. While labeling efficiency of the antibody was more excellent by enzymatic method, specific radioactivity of the antibody labeled by Iodogen method was higher than that by enzymatic method. The labeled antibody was stable in vitro and in vivo, and the labeled NCC-ST-433 was specifically accumulated in NCC-ST-433 antigen positive human tumor cell lines in vitro. The specificity of 125 I-NCC-ST-433 in vivo was found to be more excellent when this antibody was labeled by Iodogen method and acutually excellent images of H-69, a human small cell lung carcioma, were obtained 5 days after injection of 7 μg of 125 I-NCC-ST-433 per mouse. This method seemed to be promising for imaging human lung small cell carcinoma. (author)

  1. Utilization of SA-gal as clearing agent in pre-targeting RII of colon carcinoma xenograft bearing models

    International Nuclear Information System (INIS)

    Wu Hubing; Huang Zuhan; Peng Wuhe; Gao Xiao

    2001-01-01

    Objective: To conjugate galactose streptavidin (SA-gal) and use it as a clearing agent in pre-targeting radioimmunoimaging (RII) of colon carcinoma xenograft models. Methods: SA-gal was obtained by incubating galactose moiety with streptavidin at a molar ratio of 45 : 1. For imaging in vivo, biotinylated antibody radiolabelled with 131 I was injected into the nude mice bearing the colon carcinoma xenograft via the tail vein. 24 h later, SA-gal were intraperitoneally injected at a ratio of 10-fold (molar) excess to antibody. At 0.5 h and 6 h after SA-gal administration, the animals of different test groups were killed for biodistribution study or imaging. No clearing agent was administrated to the animals of two control groups and they were also killed for biodistribution study or imaging at 24 h or 30 h after injection of 131 I labelled antibody. Results: 1) Galactose moiety was bound to SA at a molar ratio of 20 : 1. 2) In pre-targeting RII, SA-gal undertook the chase effect very fast. At 0.5 h after injection, the blood level of radioactivity decreased very fast and tumor-to-blood (T/B) ratio increased from 0.32 to 1.44. At 6 h after SA-gal administration, T/B ratio reached 5.23, significantly higher than 0.41 of the control group (P 131 I-biotinylated antitumor antibody RII

  2. Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma

    Science.gov (United States)

    Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D. S.; Lo, Kwok-Wai; Ng, Chew-Hee

    2018-01-01

    Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity. PMID:29329342

  3. Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure

    Directory of Open Access Journals (Sweden)

    Hompland Tord

    2012-11-01

    Full Text Available Abstract Background High interstitial fluid pressure (IFP in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. Methods CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa or gadomelitol (MW of 6.5 kDa as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm3 and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. Results When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Conclusion Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.

  4. Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure.

    Science.gov (United States)

    Hompland, Tord; Ellingsen, Christine; Rofstad, Einar K

    2012-11-22

    High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm³ and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.

  5. Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure

    International Nuclear Information System (INIS)

    Hompland, Tord; Ellingsen, Christine; Rofstad, Einar K

    2012-01-01

    High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm 3 and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA

  6. High and low dose-rate brachytherapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Orton, C.G.

    1998-01-01

    For the brachytherapy component of the r[iation treatment of cervical carcinoma, high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due primarily to r[iation safety and other physical benefits attributed to the HDR modality. Many r[iation oncologists are reluctant to make this change because of perceived r[iobiological dis[vantages of HDR. However, in clinical practice HDR appears to be as effective as LDR but with a lower risk of late complications, as demonstrated by one randomized clinical trial and two comprehensive literature and practice surveys. The reason for this appears to be that the r[iobiological dis[vantages of HDR are outweighed by the physical [vantages. (orig.)

  7. Staging of cervical endometrial carcinoma using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Vela, A. C.; Oleaga, L.; Cura del, J. L.; Grande, J.; Grande, D.

    1999-01-01

    To demonstrate the benefits of magnetic resonance imaging (MRI) for the staging of endometrial carcinoma and to compare the results of the spin echo (SE) sequence in T2 with the results of the pos gadolinium intravenous study. We have studied 51 women diagnosed with endometrial carcinoma by means of a D and C and confirmed surgically using T1 equipment. All of them have had SE T1 axial sequences, SE in protonic density (PD) and T'' on an axial and sagittal plane carried out on them and 32 cases were studied after the administration of gadolinium intravenously (i. V.). We have valued the depth of the myometrial infiltration and the cervical invasion. The positive predictive value (PPV) and the negative predictive value (VPV) of the MRI to value the deep infiltration of the endometrium were 87.9% and 77.8% respectively. In the 32 cases where we administered gadolinium we obtained a PPV of 90% and a NPV of 83.8%, in both the SE T2 study and the contrast study. In the diagnosis of the cervical invasion we have obtained PPV and NPV values of 75% and 88.1% respectively. In the group of the 32 cases that had the contrast agent administered, we have obtained the same results in both the series: PPV of 80% and NPV of 85.2%. We have found a high correlation index between the staging using MRI and pathological anatomy, especially in stages I and II of the IFGO (International Federation of Gynecology and Obstretics) classification. The use of gadolinium has not varied the results obtained with the SE T2 series. (Author) 18 refs

  8. Air in vagina: significance in the staging of uterine cervical carcinoma

    International Nuclear Information System (INIS)

    Kim, Seung Hyup; Choi, Byung Ihn; Kang, Soon Beom; Lee, Hyo Pyo; Han, Man Chung

    1994-01-01

    To evaluate the significance of vaginal air seen on CT scan in preoperative staging of uterine cervical carcinoma. A comparison was made between CT findings of vaginal fir and true vaginal involvement status in 85 patients with uterine cervical carcinoma. CT findings were analyzed in terms of the presence or absence of vaginal air, number of CT slices in which vaginal air was seen, shape of vaginal air, and relation of vaginal air to cervical mass. Vaginal air was present in 35 patients and was absent in 50. Although the mere presence of vaginal air or multiplicity of CT slices showing vaginal air did not signify the presence of vaginal involvement, vaginal air with irregular margin or vaginal air adjacent to uterine cervical mass was suggestive of vaginal involvement. These observation of vaginal air in interpreting CT may be helpful in the preoperative staging of uterine cervical carcinoma

  9. Peritumoral interstitial fluid flow velocity predicts survival in cervical carcinoma

    International Nuclear Information System (INIS)

    Hompland, Tord; Lund, Kjersti V.; Ellingsen, Christine; Kristensen, Gunnar B.; Rofstad, Einar K.

    2014-01-01

    Background and purpose: High tumor interstitial fluid pressure (IFP) is associated with poor outcome in locally advanced carcinoma of the uterine cervix. We have recently developed a noninvasive assay of the IFP of tumors, and in this assay, the outward interstitial fluid flow velocity at the tumor surface (v 0 ) is measured by Gd-DTPA-based DCE-MRI and used as a parameter for IFP. Here, we investigated the independent prognostic significance of v 0 in cervical cancer patients given cisplatin-based concurrent chemoradiotherapy with curative intent. Patients: The study involved 62 evaluable patients from a cohort of 74 consecutive patients (Stage IB through IIIB) with a median follow-up of 5.5 years. Results: The actuarial disease-free survival (DFS) and overall survival (OS) at 5 years were 67% and 76%, respectively. Significant associations were found between v 0 dichotomized about the median value and DFS and OS, both in the total patient cohort and a subcohort of 40 Stage IIB patients. Multivariate analysis involving stage, tumor volume, lymph node status, and v 0 revealed that only v 0 provided independent prognostic information about DFS and OS. Conclusion: This investigation demonstrates a strong, independent prognostic impact of the pretreatment peritumoral fluid flow velocity in cervical cancer

  10. Hypoxia downregulates Ku70/80 expression in cervical carcinoma tumors

    International Nuclear Information System (INIS)

    Lara, Pedro Carlos; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa Maria; Bordon, Elisa; Rey, Agustin; Falcon, Orlando; Alonso, Ana Ruiz; Belka, Claus

    2008-01-01

    Hypoxia may inhibits the NHEJ DNA repair through downregulating Ku70/80 expression and combined with an increased angiogenesis and altered p53 expression would be responsible for tumor progression in cervical carcinoma

  11. Cervical osteomyelitis after carbon dioxide laser excision of recurrent carcinoma of the posterior pharyngeal wall

    NARCIS (Netherlands)

    Timmermans, A. Jacqueline; Brandsma, Dieta; Smeele, Ludi E.; Rosingh, Andert W.; van den Brekel, Michiel W. M.; Lohuis, Peter J. F. M.

    2013-01-01

    Two patients with recurrent carcinoma of the posterior pharyngeal wall, previously treated with carbon dioxide (CO2) laser excision and (chemo)radiotherapy, presented with neck pain due to cervical osteomyelitis. In one patient this led to cervical spine instability, for which a haloframe was

  12. EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma

    NARCIS (Netherlands)

    Sier, Cornelis F. M.; Zuidwijk, Kim; Zijlmans, Henry J. M. A. A.; Hanemaaijer, Roeland; Mulder-Stapel, Adri A.; Prins, Frans A.; Dreef, Enno J.; Kenter, Gemma G.; Fleuren, Gert Jan; Gorter, Arko

    2006-01-01

    Tumor progression and recurrence of cervical cancer is associated with upregulation of matrix metalloproteinase 2 (MMP-2). We evaluated the location, origin and activity of MMP-2 in cervical squamous cell carcinomas in comparison with MT1-MMP (MMP-14), TIMP-2 and extracellular matrix

  13. Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models

    Directory of Open Access Journals (Sweden)

    Wu Xianhua

    2012-08-01

    Full Text Available Abstract Background Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models. Methods PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC tissues into immunodeficient (SCID/nude mice. HER-2 gene copy number (GCN and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group. Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. Results None of the PDECX models (or their corresponding patient’s ESCC tissues harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+ in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+. A second HER-2 positive (IHC 2+ model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. Conclusions

  14. A pri-miR-218 variant and risk of cervical carcinoma in Chinese women

    International Nuclear Information System (INIS)

    Shi, Ting-Yan; Cheng, Xi; Wu, Xiaohua; Wei, Qingyi; Chen, Xiao-Jun; Zhu, Mei-Ling; Wang, Meng-Yun; He, Jing; Yu, Ke-Da; Shao, Zhi-Ming; Sun, Meng-Hong; Zhou, Xiao-Yan

    2013-01-01

    MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings

  15. Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

    Science.gov (United States)

    Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

    2003-10-01

    The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

  16. Invasive cervical carcinoma (stage IB-IIB): assessment with MR imaging

    International Nuclear Information System (INIS)

    Sironi, S.; Del Maschio, A.; Belloni, C.; Taccagni, L.

    1990-01-01

    In patients with cervical carcinoma the selection of the optimal therapy depends on the precise preoperative assessment of the extent of disease. Currently, decisions regarding the management of these patients are made on the basis of clinical (FIGO) staging that has 50% mean error rate. To investigate the value of MR imaging in staging patients with invasive cervical cancer, we performed 25 MR examinations on 23 patients with histologic diagnosis of cervical cancer. All patients were clinically considered as having stage IB or IIB disease and underwent radical hysterectomy, providing specimens for pathologic correlation. The overall accuracy of MR imaging in staging cervical carcinoma (stage IB-IIB) was 78.1%. MR imaging seems to be the most reliable preoperative modality for staging invasive cervical cancer

  17. Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft.

    Science.gov (United States)

    Ukon, Naoyuki; Zhao, Songji; Yu, Wenwen; Shimizu, Yoichi; Nishijima, Ken-Ichi; Kubo, Naoki; Kitagawa, Yoshimasa; Tamaki, Nagara; Higashikawa, Kei; Yasui, Hironobu; Kuge, Yuji

    2016-12-01

    Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl- 3 H(N)]-3'-fluoro-3'-deoxythythymidine ([ 3 H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[ 18 F]fluoro-3'-deoxythymidine ([ 18 F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [ 18 F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [ 18 F]FLT. The dynamic pattern of [ 18 F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [ 18 F]FLT phosphorylation (k 3 ) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [ 18 F]FLT forward transport (K 1 ) to reverse transport (k 2 ), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic

  18. High-dose-rate brachytherapy in uterine cervical carcinoma

    International Nuclear Information System (INIS)

    Patel, Firuza D.; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-01-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  19. Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

    Science.gov (United States)

    Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

    1996-04-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

  20. MRI of cervical carcinoma: before and after chemotherapy

    International Nuclear Information System (INIS)

    Kim, Jung Sik; Suh, Soo Jhi; Choi, Tae Jin; Lee, Tae Sung; Suh, Young Wook

    1992-01-01

    To evaluate usefulness of MR in assessment of tumor response to the chemotherapy, we prospectively studied cases of cervical carcinoma with more than 2.5cm in diameter or stage IIb or more. Three courses of chemotherapy were performed with cisplatin and 5 F-U. MR images were obtained both before and after chemotherapy. Nine of 13 patients were undertaken radical hysterectomy after chemotherapy and MR amination. MR volumetry, stage and depth of stromal invasion were compared before and after chemotherapy. And in 9 patients who underwent radical hysterectomy, comparison of pathologic and MR imaging findings were also done. The results were following. 1) All tumors dectrased in volume (m = 80.5%). 2) Five tumors (38.5%) reduced in stage, IB → CIS (1); IIA → CIS (1), IIA → IB (2), IIB → IB (1). 3) Depth of stromal invasion in MRI correlated well with that of histopathologic specimen in 7 of the 9 patients. Conclusively MR imaging is useful in assessment of tumor response to chemotherapy

  1. Stating of cervical carcinoma using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Oleaga, L.; Vela, M. C.; Grande, J.; Cura del, J. L.; Grande, D.

    1999-01-01

    The infiltration of the parametrium represents one of the most important factors that determine the prediction and treatment of cervical carcinoma. Our objective is to evaluate the utility of magnetic resonance imaging (MRI) in the staging of cervical carcinomas, to establish the reliability of this technique and to carry out a comparative study of the sequences used to demonstrate the parametrial invasion. We have carried out a retrospective study on 44 patients diagnosed with cervix neoplasia, using clinical exploration and performing a biopsy. the MRI studies have been carried out using a 1 Tesla magnet and the sequences used have been SE T1, Se proton density (PD) and T2 and dynamic GRE after administering gadolinium intravenously in the axial and sagital projections. The stages determined by MRI have been compared to the anatomo-pathological stages of the surgical specimens in cases where surgery was carried out and with the clinical stage in cases where no radical surgery was carried out. A diagnosis value of MRI has been determined to demonstrate the parametrial invasion, comparing the SE T2 sequence with the dynamic GE sequence with gadolinium. We calculate the volume of the tumour in the MRI studies to evaluate the difference of the volume between patients with tumoral stages that are clinically surgical and not surgical. MRI determines the invasion of the parametrium with a sensitivity of 88.8%, a specificity of 80% a positive value of 76.1%, a negative predictive value of 90.9% and a reliability of 83.7%. For the SE T2 sequences the sensitivity was 86.6%, the specifity 80%, the posistive predictive value 81.25%, the negative predictive value 85.7% and the reliability 83.3%. For the dynamic GE sequence with intravenous gadolinium the sensitivity was 86.6%, the specificity 86.6%, the positive predictive value 86.6%, the negative predictive value 86.6% and the reliability 86.6%. The use of the dynamic GE sequence after the intravenous administration of

  2. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    Science.gov (United States)

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  3. Squamous cell carcinoma antigen in serum for monitoring of head and neck and uterine cervical squamous cell carcinomas after radiotherapy

    International Nuclear Information System (INIS)

    Shirato, Hiroki; Ichimura, Wataru; Wakushima, Hiroshi; Nishioka, Takashi; Suzuki, Keishiro

    1993-01-01

    Squamous cell carcinoma antigen (SCC-A) in serum was serially measured during follow-up of 96 squamous cell carcinoma patients (75 head and neck cancers and 21 uterine cervical cancers), treated with radiotherapy. In 27 of the patients with head and neck cancer and in 12 of those with cervical cancer SCC-A had also been measured before radiotherapy. In this head and neck carcinoma group, the median level of SCC-A was 1.3 (95% CI: 1.2-1.9) ng/ml before radiotherapy and 1.4 (CI: 1.1-1.5) ng/ml after radiotherapy. In the cervical carcinoma group, the median SCC-A decreased significantly (p<0.001) from a pretreatment value of 7.5 (CI: 3.8-26.3) ng/ml to a posttreatment value of 0.9 (CI:<0.5-1.8) ng/ml. In the total group of 75 head and neck cancers 21 relapses occurred and in 4 of these the relapse was detected at a clinically silent stage by an elevation of serum SCC-A. The same was true for 4 of the 9 relapses that occurred in the total group of uterine cervical cancer. The study suggests that serum SCC-A may be useful for posttreatment monitoring of patients with uterine cervix cancer while its value in head and neck cancer probably is more marginal. (orig.)

  4. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

    Science.gov (United States)

    Lacava, J A; Leone, B A; Machiavelli, M; Romero, A O; Perez, J E; Elem, Y L; Ferreyra, R; Focaccia, G; Suttora, G; Salvadori, M A; Cuevas, M A; Acuña, L R; Acuña, J R; Langhi, M; Amato, S; Castaldi, J; Arroyo, A; Vallejo, C T

    1997-02-01

    To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. VNB is an active drug against ACC with moderate

  5. Rigosertib Is a More Effective Radiosensitizer Than Cisplatin in Concurrent Chemoradiation Treatment of Cervical Carcinoma, In Vitro and In Vivo

    International Nuclear Information System (INIS)

    Agoni, Lorenzo; Basu, Indranil; Gupta, Seema; Alfieri, Alan; Gambino, Angela; Goldberg, Gary L.; Reddy, E. Premkumar; Guha, Chandan

    2014-01-01

    Purpose: To compare rigosertib versus cisplatin as an effective radiosensitizing agent for cervical malignancies. Methods and Materials: Rigosertib and cisplatin were tested in cervical cancer cell lines, HeLa and C33A. A 24-hour incubation with rigosertib and cisplatin, before irradiation (2-8 Gy), was used for clonogenic survival assays. Cell cycle analysis (propidium iodide staining) and DNA damage (γ-H2AX expression) were evaluated by fluorescence-activated cell sorter cytometry. Rigosertib was also tested in vivo in tumor growth experiments on cervical cancer xenografts. Results: Rigosertib was demonstrated to induce a G 2 /M block in cancer cells. Survival curve comparison revealed a dose modification factor, as index of radiosensitization effect, of 1.1-1.3 for cisplatin and 1.4-2.2 for rigosertib. With 6-Gy irradiation, an increase in DNA damage of 15%-25% was achieved in both HeLa and C33A cells with cisplatin pretreatment, and a 71-108% increase with rigosertib pretreatment. In vivo tumor growth studies demonstrated higher performance of rigosertib when compared with cisplatin, with 53% longer tumor growth delay. Conclusions: Rigosertib was more effective than cisplatin when combined with radiation and caused minimal toxicity. These data support the need for clinical trials with rigosertib in combination therapy for patients with cervical carcinoma

  6. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

    Directory of Open Access Journals (Sweden)

    Imajoh Masayuki

    2012-08-01

    Full Text Available Abstract Background Merkel cell polyomavirus (MCPyV was identified originally in Merkel cell carcinoma (MCC, a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i the major histological type of cervical cancer is the SCC; (ii the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV. In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19% and 4/16 cervical ACs (25% were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset

  7. What are the indications of adjuvant treatment in cervical carcinoma after primary surgery?

    International Nuclear Information System (INIS)

    Dubinska, Z.; Minarik, T.

    2010-01-01

    Currently cervical cancer represents approximately 4 % of all cancer diagnoses, being the seventh most common cancer (1, 2). The standard management of patients with early cervical carcinoma is surgical treatment. Chemo radiation therapy is accepted as a standard of care for locally advanced disease (>= II B). Concurrent chemotherapy (usually cisplatin based) produced significantly improved survival and local relapse rates. The future development will be based on the improvement of sexual education, prevention and therapeutical modalities. (author)

  8. Cervical carcinoma vs endometrial carcinoma, involving both corpus and cervix : comparison of growing pattern with MR imaging

    International Nuclear Information System (INIS)

    Kim, Byung Keuk; Lee, Jin Hee; Kim, Hong; Suh, Soo Ji; Kim, Jung Sik

    2001-01-01

    To evaluate the growth pattern depicted by MR imaging and used to differentiate between uterine cervical and endometrial carcinoma where the mass involves both the uterine corpus and cervix. The tumor growth pattern observed on MR images obtained between November 1989 and January in 1999 in 37 of 784 cervical carcinomas and 9 of 47 endometrial carcinomas in which the tumor involved both the uterine corpus and cervix was analysed. The histologic type was squamous (n=29), adenocarcinomatous (n=6) or adenosquamous (n=2) in cervical carcinoma, and carcinomatous (n=8) or adenosquamous (n=1) in endometrial carcinoma. A 1.5-T (Magnetom Vision, Siemens, Germany) and a 2.0-T unit (Spectro-20000, Goldstar, Korea) were used to obtain T1-and T2-weighted axial, T2-weighted sagittal and Gd-enhanced images. Tumor involvement of the uterine cervix was classified as Cp-n, Cp-x, or Cp-b according to involvement of the endocervix, exocervix or both. Tumors of the uterine corpus were classified as involving the mucosa(U-mu), myometrium(U-my) or serosa(U-se). In 37 cases of cervical carcinoma, all three involving the endocervix(Cp-n) invaded the endometrium(U-mu), three involving both the endo- and exocervix(Cp-b) invaded the endometrium(U-mu, 1 case), myometrium(U-my, 1 case), or serosa(U-se, 1 case), and 31 involving the full-thickness of the uterine cervix(Ct) invaded the endometrium (U-mu, 6 cases) or serosa(U-se, 25 cases). In nine cases of endometrial carcinoma, three involving the endometrium(U-mu) and five involving the myometrium(U-my) invaded the endocervix(Cp-n), and one involving the serosa(U-se) invaded the full-thickness of the uterine cervix(Ct). Cervical carcinoma tended to involve the entire cervix and the full thickness of the uterine corpus, but endometrial carcinoma tended to involve the endometrium or myometrium of the uterine corpus and endocervix

  9. Radioimmunoscintigraphy of human pancreatic carcinoma xenografts in nude mice with 131I-labeled monoclonal antibody

    International Nuclear Information System (INIS)

    Tsuda, Takatoshi; Koshiba, H.; Usui, T.; Kubota, M.; Kikuchi, Kokichi; Morita, Kazuo

    1990-01-01

    Encouraged by reports of radioimmunoimaging of colorectal carcinomas and by examining an immunohistochemical report on resected pancreas cancer tissues, we studied the diagnostic potential of radioimmunoimaging with the radioiodinelabeled monoclonal antibody (MoAb; HC-1) to a human pancreas cancer cell line (HGC25) was labeled with radioiodine and injected into athymic nude mice implanted with human pancreas cancer cells. Antibody HC-1 was cleared from the circulation and accumulated significantly in the implanted tumor sites. (author)

  10. Treatment of cervical carcinoma by total hysterectomy and postoperative external irradiation

    International Nuclear Information System (INIS)

    Papavasiliou, C.; Yiogarakis, D.; Pappas, J.; Keramopoulos, A.

    1980-01-01

    The survival rates of 36 patients with early cervical carcinoma who had undergone total hysterectomy and bilateral salpingoophorectomy (THBSO) were compared to the survival rates of 41 patients who were subjected to the radical operation. As an integral part of their therapy both groups postoperatively received adequate doses of external beam supervoltage irradiation. Satisfactory results were obtained in both groups of patients. According to these results THBSO followed by postoperative radiotherapy is adequate treatment for early cervical carcinoma. In comparison to the radical operation or curietherapy alone this type of treatment has the advantage of requiring less surgical or radiotherapeutic expertise; it probably is associated with less morbidity

  11. Radioimmunoimaging of human breast carcinoma xenografts in nude mouse model with 111In-labeled new monoclonal antibody EBA-1 and F(ab')2 fragments

    International Nuclear Information System (INIS)

    Yemul, Shrishailam; Leon, J.A.; Pozniakoff, Ted; Esser, P.D.; Estabrook, Alison; Met-Path Inc., Teterboro, NJ

    1993-01-01

    Radioimmunoimaging characteristics of a new monoclonal antibody EBA-1 and its F(ab') 2 fragments utilizing nu/nu mice bearing human breast carcinoma xenografts are described. 111 In-DPTA conjugates of EBA-1 localized with tumor/blood ratios of 0.99 ± 0.10 (P 2 radioconjugates at 48 h. These results suggest that EBA-1 and its F(ab') 2 might be useful reagents in radioimmunoimaging and radioimmunotherapy. (author)

  12. Time factor and repopulation during fractionated radiotherapy. Comparison between two xenografted human squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hesselmann, S.; Horn, K.; Koenemann, S.; Schuck, A.; Willich, N.; Lindel, K.; Ruebe, C.

    2003-01-01

    Background: A series of experiments were performed to determine the local tumour control of two human squamous cell carcinoma lines in nude mice. An accelerated-fractionated radiation therapy regime is compared to a conventional-fractionated therapy regime. Material and Methods: KB is a well established human nasopharyngeal squamous cell carcinoma line (ATCC CCL 17). In nude mice KB grows as an low differentiated carcinoma. PEC MB is an undifferentiated squamous cell carcinoma of the maxillary sinus, which was successfully established in nude mice by our group 1993. Both tumors were serially passaged in nude mice. Local irradiation was given without anaesthesia under ambient conditions to air breathing animals using 18 MeV electrons of an linear accelerator (Mevatron 77, Siemens, Munich). Each dose level group consists of six to eight animals. The radiation treatments were given in ten equals fractions using graded dose levels of 2, 3, 4.5, 6 and 8 Gy. The interfraction time interval was 6 hours in the accelerated-fractionated group and 24 hours in the conventional-fractionated group. In the conventional-fractionated group a therapy break was given after 5 fractions for 72 h. The endpoint of the experiments was the dose, which was necessary to control 50% of the tumors (TCD 50 ). The TCD 50 values were calculated after 60 days (Tables 1a and 1b). Results: The experiments show, that with increasing overall treatment time of 8 3/4 days using the same number of fractions under ambient conditions the tumor control dose of the tumor KB increases from 36.3 Gy (95% CI 30.9.. 42.7) to 44.3 Gy (38.3.. 51.2). For the tumor PEC MB the tumor control dose increases from 39.5 Gy (33.4.. 46.7) to 45.5 Gy (37.0.. 56.0). Conclusion: This observed increase of the dose necessary to control the squamous cell carcinoma KB and PEC MB can be caused by repopulation of clonogenic tumors cells, however, other mechanism such as an increasing fraction of hypoxic tumor cells can not be ruled

  13. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

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    Edhyana Sahiratmadja

    2014-04-01

    Full Text Available Background Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. Methods During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. Results Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. Conclusion The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  14. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

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    Edhyana Sahiratmadja

    2015-12-01

    Full Text Available BACKGROUND Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. METHODS During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. RESULTS Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. CONCLUSION The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  15. Papillary thyroid carcinoma with tuberculous cervical lymphadenopathy mimicking metastasis

    International Nuclear Information System (INIS)

    Iqbal, M; Subhan, A.; Aslam, A.

    2011-01-01

    To determine the frequency of tuberculous cervical lymphadenopathy mimicking metastasis from papillary thyroid cancer. Study Design: Case series. Place and Duration of Study: Surgical Unit-I, Ward-3 of Jinnah Postgraduate Medical Centre, Karachi, from March 2005 to March 2010. Methodology: All patients above 12 years of age of either gender diagnosed on investigations as papillary thyroid cancer (PTC) were included in the study. Ultrasound and fine needle aspiration cytology (FNAC), neck of solitary thyroid nodules (STN) and cervical lymph nodes were done. Total thyroidectomy and excision biopsy of cervical lymph nodes was performed, histopathological results were recorded and patients were managed accordingly. Results: A total of 55 patients had PTC and 25 had cervical lymphadenopathy. Eighteen patients of PTC with cervical lymphadenopathy were diagnosed after investigations as cases of tuberculous cervical lymphadenopathy (TCL) initially considered as metastasis from PTC; 5 patients had metastasis from PTC. Two patients proved to be of reactive hyperplasia which initially showed tuberculous cervical lymphadenopathy on FNAC. So 80% patients of cervical lymphadenopathy with PTC were due to benign disease and 20% had metastasis in lymph node due to PTC. Conclusion: PTC with cervical lymphadenopathy due to co-existent tuberculosis is common. Metastasis from PTC in lymph nodes were less common than tuberculous lymphodenitis in this study. Tuberculosis should be considered before deciding for neck dissection in cases of PTC. (author)

  16. Alterations in cytokine levels in cervical carcinoma patients through radiation therapy

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    Munagala, Radha; Nagarajan, B.

    2008-01-01

    Carcinoma cervix accounts for 86-90% of all genital cancers in Indian women. This is presented with prolonged infection and impairment of immune response even after completing the radiation therapy protocol. Increase in expression of IL-6 gene in invasive cervical carcinoma was observed against CIN and normal cervix. Evaluation of infiltrating lymphocytes TIL showed considerable CD3 + and CD4 + expression which predicted better prognosis and improved survival that was negated by increased IL-6. (author)

  17. ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

    Science.gov (United States)

    Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

    2014-08-01

    Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

  18. [Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice].

    Science.gov (United States)

    Liu, G Y; Gao, Z H; Li, L; Song, T T; Sheng, X G

    2016-06-25

    To investigate the expression of Jagged1 in human epithelial ovarian carcinoma tissues and the effect of Jagged1 on growth of xenograft in nude mice. (1) Forty-eight cases of ovarian cancer and 30 cases of patients with benign epithelial ovarian tumor in the Henan Province Xinxiang Central Hospital during Feb. 2011 to Mar. 2014 were enrolled in this study. The mRNA expression of Jagged1, Notch1 and the downstream target genes Hes1, Hey1 were analyzed by using realtime PCR method. (2) The ovarian cancer xenograft models in nude mice were constructed by injecting SKOV3 cells in axillary subcutaneouswere. The nude mice were randomly divided into Jagged1 interference group, blank plasmid group and control group. Each group had 10 mice. They were transfected with pcDNA3.1(+)-siRNA-Jagged1, blank plasmid pDC3.1 and phosphate buffer, respectively. The tumor volumes and tumor masses were measured 14 days after transfection and the inhibition rate was calculated. The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues after transfection in each group was detected by using realtime PCR technique and the relative protein expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues was detected by utilizing western blot method. (1) The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in ovarian cancer tissues were higher than benign ovarian tumor tissues, the differences were statistically significant (Ptissues of nude micein Jagged1 interference group were lower than that in the other two groups, the differences were statistically significant (Ptissues of nude mice among the three groups (P>0.05). Jagged1 is highly expressed in epithelial ovarian carcinoma. Jagged1 gene interference in xenograft tumor can inhibit ovarian cancer cell growth and improve tumor suppressor rate, which probably play roles by inhibiting Notch1 signaling pathway.

  19. Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.

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    Clemens C Cyran

    Full Text Available To investigate dynamic contrast-enhanced computed tomography for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation.Colon carcinoma xenografts (HT-29 implanted subcutaneously in female athymic rats (n = 15 were imaged at baseline and after a one-week treatment with regorafenib by dynamic contrast-enhanced computed tomography (128-slice dual-source computed tomography. The therapy group (n = 7 received regorafenib daily (10 mg/kg bodyweight. Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min, endothelial permeability (PS, mL/100 mL/min, and tumor vascularity (plasma volume, % were calculated using a 2-compartment uptake model. Dynamic contrast-enhanced computed tomography parameters were validated with immunohistochemical assessments of tumor microvascular density (CD-31, tumor cell apoptosis (TUNEL, and proliferation (Ki-67.Regorafenib suppressed tumor vascularity (15.7±5.3 to 5.5±3.5%; p<0.05 and tumor perfusion (12.8±2.3 to 8.8±2.9 mL/100 mL/min; p = 0.063. Significantly lower microvascular density was observed in the therapy group (CD-31; 48±10 vs. 113±25, p<0.05. In regorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 11844±2927 vs. 5097±3463, p<0.05 were observed. Dynamic contrast-enhanced computed tomography tumor perfusion and tumor vascularity correlated significantly (p<0.05 with microvascular density (CD-31; r = 0.84 and 0.66 and inversely with apoptosis (TUNEL; r = -0.66 and -0.71.Regorafenib significantly suppressed tumor vascularity (plasma volume quantified by dynamic contrast-enhanced computed tomography in experimental colon carcinomas in rats with good-to-moderate correlations to an immunohistochemical gold standard. Tumor response biomarkers assessed by dynamic contrast-enhanced computed tomography may be a promising future

  20. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    International Nuclear Information System (INIS)

    García-Espinosa, Benjamín; Moro-Rodríguez, Ernesto; Álvarez-Fernández, Emilio

    2012-01-01

    Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited

  1. Cytologic follow-up of patients with invasive cervical carcinoma treated by radiotherapy

    International Nuclear Information System (INIS)

    Muram, D.; Curry, R.H.; Drouin, P.

    1982-01-01

    In an 11-year study done at the Ottawa Civic Hospital, cytologic assessment of 323 patients treated by radiotherapy for invasive cervical carcinoma was reviewed. The value and limitations of gynecologic cytology in the follow-up of these patients are discussed

  2. Cervical Lymph Node Metastasis: Unusual Presentation of Adenoid Cystic Carcinoma - Diagnosed By FNAC

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    Archana Buch

    2015-01-01

    Full Text Available Adenoid cystic carcinoma (ACC is a rare neoplasm that usually arises from minor salivary glands. It is characteristically locally infiltrative, exhibiting perineural invasion, has a tendency for local recurrence and prolonged clinical course. A 60 year old male, chronic smoker presented with swelling of the left cervical lymph node since two months. Examination revealed a solitary firm, non tender, non mobile left cervical swelling measuring 2 x 1 cm. Fine Needle Aspiration Cytology (FNAC was done from the cervical lymph node. The diagnosis of metastatic deposits of ACC was given. Detail examination of the oral cavity revealed a small swelling at the floor of the mouth. Biopsy of the swelling confirmed ACC on histopathological examination. An unusual feature of adenoid cystic carcinoma is the low incidence of metastases to regional lymph nodes. The case is presented to highlight its unusual presentation and utility of FNAC in rapid diagnosis.

  3. The role of hypoxia, p53, and apoptosis in human cervical carcinoma pathogenesis

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell H.; Osmanian, Cynthia; Calkins, Dennise P.; Graeber, Thomas G.; Greenspan, David L.; Kennedy, Andrew S.; Rinker, Lillian H.; Varia, Mahesh A.; DiPaolo, Joseph A.; Peehl, Donna M.; Raleigh, James A.; Giaccia, Amato J.

    1997-01-01

    Objective: Low oxygen tension in the tumor microenvironment may have an important role during tumor growth, and is of particular prognostic significance in human cervical carcinoma. Because some human papillomavirus (HPV) infections are associated with cervical neoplasia, the relationship between hypoxia and apoptosis in primary cervical epithelial cells containing HPV16 E6 and E7, intact HPV 16 genome, and HPV positive cervical carcinoma cell lines, was examined. In addition, the relationship between hypoxia and apoptosis in spontaneous human cervical carcinomas was determined in situ. Materials and Methods: Primary normal human cervical epithelial cells were infected with retroviral vectors containing HPV16 E6 and E7 or transfected with a plasmid containing the whole HPV 16 genome. Clones were selected in neomycin containing medium. Exponentially growing cells were incubated under aerobic conditions (20% O 2 ), anaerobic conditions (0.02% O 2 ), or irradiated with 6 Gy. Analysis of apoptotic cells was performed by staining with Hoechst dye and propidium iodide and viewing with a fluorescent microscope. To determine the level of expression of the apoptotic modulators p53 and Bax, immunoblots were performed on whole cell extracts from treated cells. A clinical tumor hypoxia study was conducted at the University of North Carolina utilizing pimonidazole, a 2-nitroimidazole compound which binds irreversibly to cellular macromolecules under low oxygen conditions. Nine patients were enrolled with biopsy proven squamous cell carcinoma of the cervix and no prior treatment. Biopsies of the gross tumor were obtained after pimonidazole infusion. Contiguous histological sections were analyzed for hypoxia using a immunohistochemical technique and for apoptosis using TUNEL. Results: In vitro, hypoxia uncoupled p53 from E6 mediated degradation, and stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes. In contrast

  4. A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma.

    Science.gov (United States)

    Wijetunga, Neil Ari; Ben-Dayan, Miriam; Tozour, Jessica; Burk, Robert D; Schlecht, Nicolas F; Einstein, Mark H; Greally, John M

    2016-09-20

    Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors.

  5. Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model

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    Zhao NB

    2013-01-01

    Full Text Available Ningbo Zhao,* Hong Tang,* Kai Yang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China*These authors contributed equally to this workBackground: Recent studies show that circadian rhythm changes are closely related to the occurrence and development of various tumors, such as breast, liver, and prostate. However, there are significant differences in circadian rhythm between different tumors. At present, the circadian rhythm characteristics of oral cancer remain unknown. The purpose of this study is to investigate the circadian rhythm characteristics of the in vivo growth of oral squamous cell carcinoma (OSCC.Materials and methods: Thirty-two nude mice were placed under 12-hour light/12-hour dark cycles. The human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice. After 3 weeks, eight mice were sacrificed at four time points, including 4 hours after light onset (HALO, 10 HALO, 16 HALO, and 22 HALO, during a period of 24 hours. The volume of excised tumors was measured and the proliferative index (PI and apoptotic index (AI of tumor cells were determined by flow cytometry. A cosine analysis method was used to determine whether the tumor volume, PI, and AI obeyed a circadian rhythm.Results: There was a significant circadian rhythm in the tumor volume and PI of OSCC cells. For the tumor volume, there were significant differences between the four time points. The peak and trough values of the tumor volume appeared at 3.23 HALO and 15.23 HALO, whereas the peak and trough values of PI appeared at 6.60 HALO and 18.16 HALO, respectively. However, there was no circadian rhythm in the AI of tumor cells, despite significant differences between the four time points.Conclusion: This study demonstrates, for the first time, that the tumor volume and PI of in vivo growing OSCC undergo circadian rhythms. These results support the assertion that time factor should be

  6. Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia.

    Science.gov (United States)

    Schellekens, Maaike C; Dijkman, Anneke; Aziz, Mohammad Farid; Siregar, Budiningsih; Cornain, Santoso; Kolkman-Uljee, Sandra; Peters, Lex A W; Fleuren, Gert Jan

    2004-04-01

    Cervical cancer is the second most frequently occurring type of cancer in women worldwide. A persistent infection with high-risk human papillomavirus (HPV) is a necessary causal factor in cervical carcinogenesis. The distribution of HPV types in populations has been studied worldwide. In Indonesia, however, few data are available describing the prevalence of HPV. Cervical carcinoma is the most common female cancer in Indonesia and causes high morbidity and mortality figures. With HPV vaccination studies in progress, it is important to map the HPV status of a population that would benefit greatly from future prevention programs. We tested 74 cervical cancer specimens from consecutive, newly diagnosed cervical cancer patients in the outpatient clinic of the Dr. Cipto Mangunkusumo Hospital, Jakarta. After additional staining, the formalin-fixed, paraffin-embedded tissue samples were histologically classified. HPV presence and genotype distribution were determined by SPF10 polymerase chain reaction and line probe assay. HPV DNA of 12 different HPV types was detected in 96% of the specimens. The three most common types were 16 (44%), 18 (39%) and 52 (14%). In 14% of the specimens, multiple HPV types were present. The multiple HPV types were significantly more prevalent among adenosquamous carcinomas in comparison with squamous cell carcinoma or adenocarcinoma (P = 0.014). Distribution of HPV types in Indonesia with a more prominent role for HPV 18 is slightly different from that in other parts of the world. The high amount of multiple HPV infections found in adenosquamous carcinomas may prompt further research on the pathogenesis of this type of cervical tumours.

  7. The usefulness of magnetic resonance imaging (MRI) in cervical carcinoma assessment - a preliminary report

    International Nuclear Information System (INIS)

    Tacikowska, M.; Grzesiakowska, U.; Tacikowski, T.; Sobiczewski, P.

    2002-01-01

    The aim of diagnostic imaging is not so much the detection of cervical carcinoma, but the evaluation of its stage. In view of this the aim of this study included: 1) comparison of MR results with the results of histological examinations after operations with reference to the dimensions of cervical carcinoma; 2) assessment of the sensitivity and specificity of MRl in the evaluation of parametrium infiltration; 3) analysis of the sensitivity and specificity of MRI in the evaluation of infiltration of the vagina and uterus; 4) assessment of the usefulness of this method in the detection of metastases to lymph nodes.The material consisted of pelvic MRI, obtained with 2T Elscint unit in 15 patients with cervical carcinoma, aged 37 to 73 years. All patients underwent surgical treatment within 30 days after MR. During the MR examination the following sequences were performed: SE (spin echo) T1 (longitudinal relaxation time) in axial projection before administration of gadolinium (Gd-DTPA); SE T1 in axial, frontal and sagittal projections after contrast injection and FSE (fast spin echo) T2 (transversal relaxation time) in axial, frontal and sagittal projections.1) in the assessment of cervical carcinoma dimensions MRI results are highly concordant with the results of postoperative histological examination (p = 0. 9389); 2) in the assessment of parametrium infiltration sensitivity and specificity of MRI are 75% and 100%, respectively; 3) in the assessment of the infiltration of the vagina and uterine corpus the sensitivity and specificity of MRI imaging were respectively 100% and 85%; 100% and 100%; 4) in the detection of lymph node metastases MRI sensitivity was 67% and its specificity 100%. In patients with cervical carcinoma MRI is a valuable method for the assessment of tumour dimensions, parametrium infiltration, infiltration of the vagina and uterine corpus.(author)

  8. Stating of cervical carcinoma using magnetic resonance imaging; Estadificacion del carcinoma de cervix por resonancia magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Oleaga, L.; Vela, M. C.; Grande, J.; Cura del, J. L.; Grande, D. [Hospital de Basurto. Bilbao (Spain)

    1999-07-01

    The infiltration of the parametrium represents one of the most important factors that determine the prediction and treatment of cervical carcinoma. Our objetive is to evaluate the utility of magnetic resonance imaging (MRI) in the staging of cervical carcinomas, to establish the reliability of this technique and to carry out a comparative study of the sequences used to demonstrate the parametrial invasion. We have carried out a retrospective study on 44 patients diagnosed with cervix neoplasia, using clinical exploration and performing a biopsy. the MRI studies have been carried out using a 1 Tesla magnet and the sequences used have been SE T1, Se proton density (PD) and T2 and dynamic GRE after administering gadolinium intravenously in the axial and sagital projections. The stages determined by MRI have been compared to the anatomopathological stages of the surgical specimens in cases where surgery was carried out and with the clinical stage in cases where no radical surgery was carried out. A diagnosis value of MRI has been determined to demonstrate the parametrial invasion, comparing the SE T2 sequence with the dynamic GE sequence with gadolinium. We calculate the volume of the tumour in the MRI studies to evaluate the difference of the volume between patients with tumoral stages that are clinically surgical and not surgical. MRI determines the invasion of the parametrium with a sensitivity of 88.8%, a specificity of 80% a positive value of 76.1%, a negative predictive value of 90.9% and a reliability of 83.7%. For the SE T2 sequences the sensitivity was 86.6%, the specifity 80%, the posistive predictive value 81.25%, the negative predictive value 85.7% and the reliability 83.3%. For the dynamic GE sequence with intravenous gadolinium the sensitivity was 86.6%, the specifity 86.6%, the posistive predictive value 86.6%, the negative predictive value 86.6% and the reliability 86.6%. The use of the dynamic GE sequence after the intravenous administration of

  9. Dll4 blockade potentiates the anti-tumor effects of VEGF inhibition in renal cell carcinoma patient-derived xenografts.

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    Kiersten Marie Miles

    Full Text Available The Notch ligand Delta-like 4 (Dll4 is highly expressed in vascular endothelium and has been shown to play a pivotal role in regulating tumor angiogenesis. Blockade of the Dll4-Notch pathway in preclinical cancer models has been associated with non-productive angiogenesis and reduced tumor growth. Given the cross-talk between the vascular endothelial growth factor (VEGF and Delta-Notch pathways in tumor angiogenesis, we examined the activity of a function-blocking Dll4 antibody, REGN1035, alone and in combination with anti-VEGF therapy in renal cell carcinoma (RCC.Severe combined immunodeficiency (SCID mice bearing patient-derived clear cell RCC xenografts were treated with REGN1035 and in combination with the multi-targeted tyrosine kinase inhibitor sunitinib or the VEGF blocker ziv-aflibercept. Immunohistochemical and immunofluorescent analyses were carried out, as well as magnetic resonance imaging (MRI examinations pre and 24 hours and 2 weeks post treatment. Single agent treatment with REGN1035 resulted in significant tumor growth inhibition (36-62% that was equivalent to or exceeded the single agent anti-tumor activity of the VEGF pathway inhibitors sunitinib (38-54% and ziv-aflibercept (46%. Importantly, combination treatments with REGN1035 plus VEGF inhibitors resulted in enhanced anti-tumor effects (72-80% growth inhibition, including some tumor regression. Magnetic resonance imaging showed a marked decrease in tumor perfusion in all treatment groups. Interestingly, anti-tumor efficacy of the combination of REGN1035 and ziv-aflibercept was also observed in a sunitinib resistant ccRCC model.Overall, these findings demonstrate the potent anti-tumor activity of Dll4 blockade in RCC patient-derived tumors and a combination benefit for the simultaneous targeting of the Dll4 and VEGF signaling pathways, highlighting the therapeutic potential of this treatment modality in RCC.

  10. Doxorubicin combined with low intensity ultrasound suppresses the growth of oral squamous cell carcinoma in culture and in xenografts

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    Haixia Fan

    2017-11-01

    Full Text Available Abstract Background Oral squamous cell carcinoma (OSCC invades surrounding tissues by upregulating matrix metalloproteinases (MMPs -2 and −9, which causes over-expression of the Hedgehog signaling proteins Shh and Gli-1 and degradation of the extracellular matrix, thereby creating a “highway” for tumor invasion. We explored the potential of low intensity ultrasound (LIUS and doxorubicin (DOX to inhibit the formation of this “highway”. Methods MTT assays were used to examine OSCC cell viability after exposure to LIUS and DOX. The cell morphological changes and ultrastructure were detected by scanning electron microscopy and transmission electron microscopy. Endogenous autophagy-associated proteins were analyzed by immunofluorescent staining and western blotting. Cell migration and invasion abilities were evaluated by Transwell assays. Collagen fiber changes were evaluated by Masson’s trichrome staining. Invasion-associated proteins were analyzed by immunohistochemistry and western blotting. Results LIUS of 1 W/cm2 increased the in vitro DOX uptake into OSCC by nearly 3-fold in three different cell lines and induced transient autophagic vacuoles on the cell surface. The combination of LIUS and 0.2 μg/ml DOX inhibited tumor cell viability and invasion, promoted tumor stromal collagen deposition, and prolonged the survival of mice. This combination also down-regulated MMP-2, MMP-9, Shh and Gli-1 in tumor xenografts. Collagen fiber expression was negatively correlated with the expression of these proteins in human OSCC samples. Conclusions Our findings suggest that effective low dosages of DOX in combination with LIUS can inhibit cell proliferation, migration and invasion, which might be through MMP-2/9 production mediated by the Hedgehog signaling pathway.

  11. Suppressor of fused (Sufu) promotes epithelial-mesenchymal transition (EMT) in cervical squamous cell carcinoma

    Science.gov (United States)

    Zhang, Ziyu; Zou, Yang; Liang, Meirong; Chen, Yuanting; Luo, Yong; Yang, Bicheng; Liu, Faying; Qin, Yunna; He, Deming; Wang, Feng; Huang, Ouping

    2017-01-01

    Suppressor of fused is essential for the maximal activation of Sonic Hedgehog signaling in development and tumorigenesis. However, the role of Sufu in cervical carcinoma remains unknown. Here, we report new findings of Sufu in regulating the epithelial-to-mesenchymal transition through the FoxM1 transcriptional modulation by 14-3-3ζ protein in cervical carcinoma. Sufu is overexpressed in cervical squamous cell carcinoma and its level in clinical tumor tissues is positively correlated with 14-3-3ζ. Functionanlly, siSufu remarkably prevents the cancer cell migration and invasion. We further demonstrate that the transcriptional activity of Sufu is increased by FoxM1, of which stability is promoted by 14-3-3ζ. Knockdown FoxM1 decreases the invasion of SiHa cells and reconstitution of Sufu rescues the invasion of these cells.Finally, overexpression of Sufu is significantly associated with differentiation grade, FIGO stage, Depth of stromal invasion and vascular cancer embolus. Our findings highlight a novel role for Sufu in cervical carcinogenesis. PMID:29371981

  12. The value of lymphoscintigraphy for cervical sentinel lymph node detection in patients with clinically N0 oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Liu Sheng; Jiang Ningyi; Lu Xianping; Liang Jiugen

    2005-01-01

    Objective: To evaluate the value of lymphoscintigraphy for cervical sentinel lymph node (SLN) detection in patients with oral squamous cell carcinoma. Methods: Twenty-one patients with clinically N 0 oral squamous carcinoma underwent preoperative lymphoscintigraphy and intraoperative methylene blue location. The results were compared with pathological findings. Results: 1) The sensitivity of lymphoscintigraphy for detecting SLN was 100%(21/21), and methylene blue was 85% (17/20). 2)Both SLN biopsy and cervical ablative dissection confirmed that 33.3% (7/21) patients were with cervical lymph node metastasis. Fourteen non-metastatic SLNs comfirmed by biopsy were also proved with the findings of neck dissection, and the specificity was 100%. Conclusion: Lymphoscintigraphy can detect the cervical SLN and accurately predict cervical lymph node metastasis in patients with oral squamous cell carcinoma.(authors)

  13. Role of computed tomography (CT scan in staging of cervical carcinoma

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    T V Prasad

    2014-01-01

    Full Text Available Background & objectives: Staging of cervical carcinoma is done clinically using International Federation of Obstetrics and Gynecology (FIGO guidelines. It is based on physical examination findings and also includes results of biopsy, endoscopy and conventional radiological tests like chest radiograph, intravenous urography and barium enema. These conventional radiological investigations have largely been replaced by computed tomography (CT and magnetic resonance imaging (MRI at present. FIGO staging system does not consider CT and MRI mandatory; however, use of these modalities are encouraged. This prospective study was conducted to determine the role of CT in staging work up in women diagnosed with cervical carcinoma. Methods: Fifty three women diagnosed with cervical carcinoma were evaluated with contrast enhanced CT scan of abdomen and pelvis. CT scan images were especially evaluated to determine tumour size, invasion of parmetrium, pelvic walls, rectum, urinary bladder and ureters, pelvic or retroperitoneal lymphadenopathy and distant metastases. CT findings were associated with clinical findings and staging, including findings from cystoscopy and sigmoidoscopy. Results: There was a poor agreement between clinical and CT staging of cervical carcinoma. Primary tumour was demonstrated on CT in 36 (70% of 53 patients. CT underestimated the parametrial, vaginal and pelvic wall invasion when compared with physical examination. CT overestimated the urinary bladder and rectal invasion when compared with cysto-sigmoidoscopy, however, CT had 100 per cent negative predictive value (NPV to exclude bladder and rectal involvement. CT detection of lymph node enlargement and lung metastases influenced the management. Interpretation & conclusions: Our findings show that CT scan does not reliably correlate with clinical FIGO staging of cervical cancer. However, it can detect urinary obstruction as well as nodal or distant metastases and thus improves the

  14. Cervical carcinoma metastasizing to uveal tissue manifesting as pseudohypopyon

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    Vinay Gupta

    2017-01-01

    Full Text Available The metastasis to the eye in a patient of carcinoma of the cervix is rare. A case of carcinoma cervix in a 56-year-old female is described who presented with full chamber pseudohypopyon and deep vascularization in inferior quadrant of the cornea in the left eye. Magnetic resonance imaging revealed features suggestive of ocular metastasis in the anterior part of the uveal tract. Diagnosis was confirmed on cytology which showed features of squamous cell carcinoma. A high level of clinical suspicion in advanced cases of malignancies will help in early detection of ocular metastasis with unusual presentations.

  15. Carcinoma of the cervical stump: comparison of radiation therapy factors, survival and patterns of failure with carcinoma of the intact uterus

    International Nuclear Information System (INIS)

    Igboeli, P.; Kapp, D.S.; Lawrence, R.; Schwartz, P.E.

    1983-01-01

    Eighty-nine patients with previously untreated invasive carcinoma of the cervical stump were seen at Yale-New Haven Hospital from 1953 through 1977. This represented 9.4% of the carcinomas of the cervix seen during this time period. Eighty-five of the 89 patients (95.5%) had ''true'' cancers of the cervical stump diagnosed 2 years or more after subtotal hysterectomy, while 4 of the 89 patients (4.5%) had ''coincident'' cancers diagnosed within 2 years of the subtotal hysterectomy. All cervical cancers were staged by the F.I.G.O. classification. Patient characteristics, methods of management, failure sites and survival of patients with carcinoma of the cervical stump were compared to those patients with carcinoma in the intact uterus. Patients with cervical stump cancers were treated in a similar manner to those with carcinomas of the intact uterus, using a combination of external beam irradiation and intracavitary radium. The stump cancer patients had a similar stage distribution to the patients with cancers of the intact uterus but, on the average, they were older and received less irradiation. The patterns of failure were similar on a stage for stage basis, but the survival and disease-free survival for stump cancer patients were superior to those of the patients with carcinoma of the intact uterus

  16. Ectopic cervical thymoma mimicking as papillary thyroid carcinoma: A diagnostic dilemma

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    Thakur Abhijit

    2010-04-01

    Full Text Available Ectopic cervical thymomas are often confused with thyroid or parathyroid swellings due to their anatomical positioning. Predominant epithelial thymoma can be misdiagnosed as papillary thyroid carcinoma on fine needle aspiration and lymph node metastasis of epithelial tumor on frozen section. Predominantly lymphocytic thymomas have often been misinterpreted as Hashimoto′s thyroiditis or malignant lymphoma, either by fine needle aspiration or on frozen section analysis. If cytology is doubtful and is not correlating with clinical, anatomical and surgical findings; immunohistochemistry is a very important tool in such cases to give final answer. Thyroid cell specific proteins such as thyroglobulin, thyroid transcription factor-1, thyroperoxidase and dipeptidyl aminopeptidase-4, neuroendocrine markers chromogranin, calcitonin and parathyroid hormone could be used to rule out thyroid or parathyroid origin. We present such rare case of ectopic cervical thymoma mimicking as papillary thyroid carcinoma.

  17. Immunological disturbances and their role in treatment for cervical carcinoma

    International Nuclear Information System (INIS)

    Grinevich, Yu.A.; Dzyubko, N.Ya.; Kokhanevich, E.V.

    1983-01-01

    The study is concerned with immunologic status (cell-mediated and humoral immunity) as a factor influencing the choice of scheme of treatment for carcinoma of cervix uteri. The indexes of immunocompetence should be taken into account in planning the differential treatment of precancer and early forms of carcinoma of cervix uteri. Radiation treatment exerts an immunosuppressive effect. However, immunologic indexes are not affected considerably by laser destruction or surgery. Cryodestruction has a beneficial effect on cell-mediated immunity. Considering these effects as well as the long-term results of different orocedures of treatment, laser coagulation, cryogenic destruction or diathermoconization should be recommended for management of carcinoma in situ of cervix uteri, and extensive extirpation of the uterus, unattended by radiation, for Tla

  18. Palliative radiotherapy for cervical carcinoma, a systematic review

    International Nuclear Information System (INIS)

    Lonkhuijzen, Luc van; Thomas, Gillian

    2011-01-01

    Purpose: Worldwide, particularly in developing countries, many women present with advanced stage cervical cancer for which palliative radiotherapy is the treatment of choice or may be the only available treatment. The purpose of this study was to determine from the literature the optimal palliative radiation scheme for the treatment of advanced cervical cancer. Design: A systematic literature review up to January 2010 was performed in Medline, Embase, the Cochrane database, CinHL and Google Scholar using a combination of synonyms for: cervical cancer, palliative treatment and radiation therapy. No limitations were applied for language or study types. For included papers data were extracted and described. Results: Only eight papers were identified and none compared the results of different fractionation schemes. Most used observational retrospective study design with considerable sources of bias. No studies used validated endpoints for symptom relief nor did they include measures of the quality of life. Several papers described the experience with single or multiple monthly 10 Gy doses or with a higher total dose delivered in 2-4 fractions within 48 h to 1 week. Studies report varying amounts of relief from bleeding. The effect on other symptoms such as pain and discharge is not evaluable. Acute and late toxicity is poorly documented. Conclusion: There is a dearth of information in the current literature to guide selection of an optimal palliative radiation schedule for treatment of patients with advanced cervical cancer. Based on this review and information from other solid tumors, there is no evidence to support the common belief that better and longer palliation is achieved with a high dose delivered in multiple smaller fractions. There is a clear need for comparative studies of different radiation fractionation schedules in order to identify an optimal palliative radiation scheme. These studies require the use of validated endpoints to measure specific symptom

  19. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  20. Clinical significations of G2-M stage partial synchronization on radiation therapies of uterine cervical carcinomas

    International Nuclear Information System (INIS)

    Sasaki, Hiroshi

    1981-01-01

    The present study revealed that irradiation-induced changes of repopulation and redistribution played an important role in radiosensitivity and cure process of human uterine cervical carcinoma. DNA measurements by a microspectrophotometer were made on Feulgen stained biopsy specimens obtained from 20 patients. On the other hand, flow-microfluorometric measurements with Fried's computed cell cycle analysis were made on transplanted human cervical carcinomas. The mean nuclear DNA amount of human cervical carcinoma cells increased according as the irradiation doses increase until 2,000 rad. Moreover, as regards with the mean nuclear diameter of cancer cells the same phenomenon was recognized, and there was an interrelation between the increase of mean nuclear DNA amount and that of mean nuclear diameter. This phenomenon was proved in nuclear DNA analysis by flow-microfluorometric measurements on transplanted human cervical carcinoma in nude mice. Computed cell cycle analysis of F.M.F. data demonstrated that this phenomenon was due to irradiation-induced changes of repopulation and redistribution. That is to say, irradiation induces the increase of cycling cells and then partial synchronization to G2-M stage. Examination of the interrelation between this phenomenon at 500 rad and 5 years survival rate demonstrated that there was more increase of nuclear DNA amount in the good prognosis group than in the poor prognosis group. Estimation of residual cells near the G1 stage at 2,000 rad demonstrated that there were more residual cells near the G1 stage in the poor prognosis group than in the good prognosis group. (author)

  1. Down-regulation of the expression of CCAAT/enhancer binding protein α gene in cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Pan, Zemin; Shao, Renfu; Zheng, Weinan; Zhang, Jinli; Gao, Rui; Li, Dongmei; Guo, Xiaoqing; Han, Hu; Li, Feng; Qu, Shen

    2014-01-01

    Cervical carcinoma is the second most common cancer and is an important cause of death in women worldwide. CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that regulate cellular differentiation and proliferation in a variety of tissues. However, the role of C/EBPα gene in cervical cancer is still not clear. We investigated the expression of C/EBPα gene in cervical squamous cell carcinoma. C/EBPα mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. C/EBPα protein level was measured by immunohistochemistry. Methylation in the promoter of C/EBPα gene was detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBPα expression vector. C/EBPα expression in HeLa cells was examined and HeLa cell proliferation was measured by MTT assay and HeLa cells migration was analyzed by matrigel-coated transwell migration assays. There were significant difference in C/EBPα protein expression between chronic cervicitis and cervical carcinoma (P < 0.001). CEBPα mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues (P < 0.01). Methylation of the promoter of CEBPα gene in CpG 5, CpG-14.15, CpG-19.20 were significantly higher in cervical cancer than in normal cervical tissues (P < 0.05, P < 0.01, P < 0.05, respectively). CEBPα pcDNA3.1 construct transfected into HeLa cells inhibited cell proliferation and decreased cell migration. Our results indicate that reduced C/EBPα gene expression may play a role in the development of cervical squamous cell carcinoma

  2. Papillomavirus genomes in human cervical carcinoma: Analysis of their integration and transcriptional activity

    International Nuclear Information System (INIS)

    Matulic, M.; Soric, J.

    1994-01-01

    Eighty-four biopsies derived from cervical tissues were analyzed for the presence of human papillomavirus (HPV) DNA types 6, 16 and 18 using Southern blot hybridization. HPV 6 was found in none of the cervical biopsies, and HPV types 16 and 18 were found in 44% of them. The rate of HPV 16/18 positive samples increased proportionally to the severity of the lesion. In normal tissue there were no positive samples, in mild and moderate dysplasia HPV 16/18 was present in 20% and in severe dysplasia and invasive carcinomas in 37 and 50%, respectively. In biopsies from 13 cases with squamous cell carcinoma of the uterine cervix and CIN III lesions HPV 16 was integrated within the host genome. It was concluded that the virus could be integrated at variable, presumably randomly selected chromosomal loci and with different number of copies. Transcription of HPV 16 and 18 was detected in one cervical cancer in HeLa cells, respectively. These results imply that HPV types 16 and 18 play an etiological role in the carcinogenesis of human cervical epithelial cells. (author)

  3. Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: a single institution experience from Thailand

    International Nuclear Information System (INIS)

    Tharavichitkul, Ekkasit; Lorvidhaya, Vicharn; Kamnerdsupaphon, Pimkhuan; Sukthomya, Vimol; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Supawongwattana, Bongkoch; Pukanhaphan, Nantaka; Galalae, Razvan; Chitapanarux, Imjai

    2016-01-01

    To report the results of combined chemoradiation (CCRT) with cisplatin versus carboplatin in locally advanced cervical carcinoma. From 2009 to 2013, 255 patients with stage IIB-IVA cervical carcinoma, according to FIGO staging were prospectively assigned to be treated with pelvic radiotherapy followed by brachytherapy given concurrently with cisplatin or carboplatin in the treatment of locally advanced cervical cancer. Treatment outcomes and toxicitiy were evaluated. Two-hundred and thirteen patients could be evaluated. At a median follow-up time of 43 months (6–69 months), the 3-year local control, disease-free survival, metastasis-free survival and overall survival rates were 93, 80.8, 85.0 and 87.3 %, respectively. No statistical difference in terms of local control, disease-free survival, metastasis-free survival and overall survival rates between cisplatin and carboplatin treatments was observed in this study. Eighty-six percents of the patients in the carboplatin group could receive more than 4 cycles, while there were only 72 % in the cisplatin group who completed more than 4 cycles (p = 0. 02). In terms of acute toxicity, cisplatin caused significantly more anemia (p = 0.026), neutropenia (p = 0. 044) and nephrotoxicity (p = 0. 031) than carboplatin. No difference in late toxicity was observed in this study. Carboplatin yielded comparable results to cisplatin in concurrent chemo-radiation for locally advanced cervical cancer. In addition, carboplatin was associated with a better compliance rate and was associated with less of anemia, neutropenia and nephrotoxicity

  4. A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma

    Science.gov (United States)

    Wijetunga, Neil Ari; Ben-Dayan, Miriam; Tozour, Jessica; Burk, Robert D.; Schlecht, Nicolas F.; Einstein, Mark H.; Greally, John M.

    2016-01-01

    Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors. PMID:27557505

  5. Complications after radiotherapy and radical hysterectomy in early-stage cervical carcinoma

    International Nuclear Information System (INIS)

    Gerdin, E.; Cnattingius, S.; Johnson, P.

    1995-01-01

    Objective: To evaluate the overall complications, major as well as minor, in patients treated for early-stage cervical carcinoma as related to treatment parameters. Methods: In this retrospective study, 167 consecutive patients with early-stage cervical carcinoma treated with preoperative radiotherapy and radical hysterectomy were investigated. Clinical data were collected from the medical files. Results: Transient or permanent complications appeared in up to half of all patients. Seven percent exhibited intraoperative complications and 35% suffered from early postoperative urinary tract problems; most frequently urinary tract infection. After one year, the urinary tract complications dominated; voidance difficulties and incontinence being most common. Gastrointestinal complications occurred in 15% of patients. Lymphedema appeared during the first year in 21% of the patients but several of the mild or moderate cases improved after the first year. The relative risk of lymphedema was increased with shorter duration of surgery, extensive preoperative irradiation to the bladder and after external postoperative irradiation. Some form of late sequelae remained in every fifth patient, and every fourth patient, aged 23-44 years, periodically suffered from vasomotor symptoms despite estrogen replacement therapy. Conclusion: The complications after radiotherapy and radical hysterectomy in early stage cervical carcinoma suggest that attempts should be made to evaluate effective treatments designed to minimize risk to the patients. (au) 29 refs

  6. Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hanhui [Shanghai Medical College of Fudan University, Shanghai 200032 (China); Zhao, Wenrong [Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011 (China); Yang, Dan, E-mail: yangdandr@gmail.com [Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai 200040 (China)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Upregulation of Skp2 by IL-6 or Stat3 activation. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through bound to its promoter region. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through recruitment of P300. Black-Right-Pointing-Pointer Stat3 activation decreases the P27 stability. -- Abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.

  7. Transcriptional Inhibition of the Human Papilloma Virus Reactivates Tumor Suppressor p53 in Cervical Carcinoma Cells

    Science.gov (United States)

    Kochetkov, D. V.; Ilyinskaya, G. V.; Komarov, P. G.; Strom, E.; Agapova, L. S.; Ivanov, A. V.; Budanov, A. V.; Frolova, E. I.; Chumakov, P. M.

    2009-01-01

    Inactivation of tumor suppressor p53 accompanies the majority of human malignancies. Restoration of p53 function causes death of tumor cells and is potentially suitable for gene therapy of cancer. In cervical carcinoma, human papilloma virus (HPV) E6 facilitates proteasomal degradation of p53. Hence, a possible approach to p53 reactivation is the use of small molecules suppressing the function of viral proteins. HeLa cervical carcinoma cells (HPV-18) with a reporter construct containing the b-galactosidase gene under the control of a p53-responsive promoter were used as a test system to screen a library of small molecules for restoration of the transcriptional activity of p53. The effect of the two most active compounds was studied with cell lines differing in the state of p53-dependent signaling pathways. The compounds each specifically activated p53 in cells expressing HPV-18 and, to a lesser extent, HPV-16 and exerted no effect on control p53-negative cells or cells with the intact p53-dependent pathways. Activation of p53 in cervical carcinoma cells was accompanied by induction of p53-dependent CDKN1 (p21), inhibition of cell proliferation, and induction of apoptosis. In addition, the two compounds dramatically decreased transcription of the HPV genome, which was assumed to cause p53 reactivation. The compounds were low-toxic for normal cells and can be considered as prototypes of new anticancer drugs. PMID:17685229

  8. Complications after radiotherapy and radical hysterectomy in early-stage cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gerdin, E. [Univ. Hospital, Dept. of Obstetrics and Gynecology, and Gynecologic Oncology, Uppsala (Sweden); Cnattingius, S. [Univ. Hospital, Dept. of Social Medicine, Uppsala (Sweden); Johnson, P. [Univ. Hospital, Dept. of Obstetrics and Gynecology, Uppsala (Sweden)

    1995-08-01

    Objective: To evaluate the overall complications, major as well as minor, in patients treated for early-stage cervical carcinoma as related to treatment parameters. Methods: In this retrospective study, 167 consecutive patients with early-stage cervical carcinoma treated with preoperative radiotherapy and radical hysterectomy were investigated. Clinical data were collected from the medical files. Results: Transient or permanent complications appeared in up to half of all patients. Seven percent exhibited intraoperative complications and 35% suffered from early postoperative urinary tract problems; most frequently urinary tract infection. After one year, the urinary tract complications dominated; voidance difficulties and incontinence being most common. Gastrointestinal complications occurred in 15% of patients. Lymphedema appeared during the first year in 21% of the patients but several of the mild or moderate cases improved after the first year. The relative risk of lymphedema was increased with shorter duration of surgery, extensive preoperative irradiation to the bladder and after external postoperative irradiation. Some form of late sequelae remained in every fifth patient, and every fourth patient, aged 23-44 years, periodically suffered from vasomotor symptoms despite estrogen replacement therapy. Conclusion: The complications after radiotherapy and radical hysterectomy in early stage cervical carcinoma suggest that attempts should be made to evaluate effective treatments designed to minimize risk to the patients. (au) 29 refs.

  9. Treatment of nasopharyngeal carcinoma cells with the histone-deacetylase inhibitor abexinostat: cooperative effects with cis-platin and radiotherapy on patient-derived xenografts.

    Directory of Open Access Journals (Sweden)

    Mélanie Gressette

    Full Text Available EBV-related nasopharyngeal carcinomas (NPCs still raise serious therapeutic problems. The therapeutic potential of the histone-deacetylase (HDAC inhibitor Abexinostat was investigated using 5 preclinical NPC models including 2 patient-derived xenografts (C15 and C17. The cytotoxicity of Abexinostat used either alone or in combination with cis-platin or irradiation was assessed in vitro by MTT and clonogenic assays using 2 EBV-negative (CNE1 and HONE1 and 3 EBV-positive NPC models (C15, C17 and C666-1. Subsequently, the 3 EBV-positive models were used under the form of xenografts to assess the impact of systemic treatments by Abexinostat or combinations of Abexinostat with cis-platin or irradiation. Several cell proteins known to be affected by HDAC inhibitors and the small viral non-coding RNA EBER1 were investigated in the treated tumors. Synergistic cytotoxic effects of Abexinostat combined with cis-platin or irradiation were demonstrated in vitro for each NPC model. When using xenografts, Abexinostat by itself (12.5 mg/kg, BID, 4 days a week for 3 weeks had significant anti-tumor effects against C17. Cooperative effects with cis-platin (2 mg/kg, IP, at days 3, 10 and 17 and irradiation (1 Gy were observed for the C15 and C17 xenografts. Simultaneously two types of biological alterations were induced in the tumor tissue, especially in the C17 model: a depletion of the DNA-repair protein RAD51 and a stronger in situ detection of the small viral RNA EBER1. Overall, these results support implementation of phase I/II clinical trials of Abexinostat for the treatment of NPC. A depletion of RAD51 is likely to contribute to the cooperation of Abexinostat with DNA damaging agents. Reduction of RAD51 combined to enhanced detection of EBER 1 might be helpful for early assessment of tumor response.

  10. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model.

    Science.gov (United States)

    Kurundkar, Deepali; Srivastava, Ritesh K; Chaudhary, Sandeep C; Ballestas, Mary E; Kopelovich, Levy; Elmets, Craig A; Athar, Mohammad

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    Energy Technology Data Exchange (ETDEWEB)

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  12. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    International Nuclear Information System (INIS)

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.; Ballestas, Mary E.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  13. Prognostic implication of simultaneous anemia and lymphopenia during concurrent chemoradiotherapy in cervical squamous cell carcinoma.

    Science.gov (United States)

    Cho, Oyeon; Chun, Mison; Oh, Young-Taek; Noh, O Kyu; Chang, Suk-Joon; Ryu, Hee-Sug; Lee, Eun Ju

    2017-10-01

    Radioresistance often leads to poor survival in concurrent chemoradiotherapy-treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy-treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy-treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan-Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0

  14. Value of Lymphography before and after Radical Hysterectomy in Carcinoma of the Uterine Cervic

    International Nuclear Information System (INIS)

    Kim, Choon Yul; Oh, Yung Ho; Yang, Woo Jin; Bahk, Yong Whee

    1983-01-01

    Radiological demonstration of lymph vessels and lymph nodes may be achieved only by direct lymphography, which is performed by injecting contrast material directly into the lymph vessels, lymph nodes, or occasionally into lymph cysts. Clinical lymphography is performed essentially according to the direct technique of Kinmonth (1952 and 1954). Lymphography has become a routine procedure in patients with carcinoma of the uterine cervix. Thorough assessment of the extent of carcinoma of the uterine cervix is necessary to the intelligent management of any patient with uterine carcinoma. This presentation is to outline the technique of lymphangio-adenography (lymphography), lymphographic finding and diagnostic criteria of the cervical carcinoma, and evaluation of the accuracy of lymphographic diagnosis in cervical carcinoma. A retrospective review of the lymphograms of 145 patients with carcinoma of the uterine cervix was undertaken. All lymphograms were performed at Kang Nam St. Mary's and St. Mary's Hospitals, Catholic Medical College from 1975 to 1982. Of these patients 87 were got radical hysterectomy and lymphographic diagnosis was compared with tissue pathology of the lymph nodes removed, and determined the diagnostic accuracy of lymphography. Lymphography can make a significant contribution in the pretreatment assessment of patients with carcinoma of the uterine cervix. Strick adherence to rigid criteria will yield excellent pathologic correlation in the event of a positive radiographic diagnosis of metastatic carcinoma. Once a positive diagnosis is made, it should influence the management of the cancer patients. The results were as follow: 1. The accuracy of lymphography in diagnosing lymph node matastasis of carcinoma of the uterine cervix was 85.1%, 82.4% in sensitivity and 86.8% in specificity. 2. Metastic lymph nodes were moderately to markedly enlarged and irregular in shape and shown motheaten marginal filling defects in 92.7%. These were ranged from 3mm

  15. Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Li, Xiucan; Wang, Yiguo; Zhao, Yongfei; Liu, Jianheng; Xiao, Songhua; Mao, Keya

    2017-11-15

    MINI: A 3D printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma. The personalized porous implant printed in Ti6AL4V provided excellent physicochemical properties and biological performance, including biocompatibility, osteogenic activity, and bone ingrowth effect. A unique case report. A three-dimensional (3D) printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma in a middle-age female patient. Papillary thyroid carcinoma is a malignant neoplasm with a relatively favorable prognosis. A metastatic lesion in multilevel cervical spine (C2-C4) destroys neurological functions and causes local instability. Radical excision of the metastasis and reconstruction of the cervical vertebrae sequence conforms with therapeutic principles, whereas the special-shaped multilevel upper-cervical spine requires personalized implants. 3D printing is an additive manufacturing technology that produces personalized products by accurately layering material under digital model control via a computer. Reporting of this recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in the literature. Anterior-posterior surgery was performed in one stage. Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with insertion of a personalized implant manufactured by 3D printing technology, were performed to rebuild the cervical spine sequences. The porous implant was printed in Ti6AL4V with perfect physicochemical properties and biological performance, such as biocompatibility and osteogenic activity. Finally, lateral mass screw fixation was performed via a posterior approach. Patient neurological function gradually improved after the surgery. The patient received 11/17 on the Japanese Orthopedic Association scale and ambulated with a personalized skull-neck-thorax orthosis on

  16. Oxygenation status of cervical carcinomas before and during spinal anesthesia for application of brachytherapy

    International Nuclear Information System (INIS)

    Weitmann, H.D.; Knocke, T.H.; Poetter, R.; Gustorff, B.; Vaupel, P.

    2003-01-01

    Background and Purpose: To date, no information is available concerning the impact of spinal anesthesia on the oxygenation status of carcinomas of the uterine cervix. The aim of this study was therefore to determine the influence of spinal anesthesia on the oxygenation status of cervical carcinomas. Patients and Methods: In ten patients with cervical carcinoma who received spinal anesthesia for a first application of brachytherapy, intratumoral pO 2 measurements (pO 2 histography system, Eppendorf-Netheler-Hinz, Hamburg, Germany) were performed. Systemic parameters were documented prior to and during spinal anesthesia. Patients breathed room air spontaneously. For further evaluation, all intratumoral pO 2 values were pooled, and overall median pO 2 values and fractions of hypoxic pO 2 values ≤ 5 mm Hg were calculated. Overall median pO 2 values in the subcutis were also calculated. Results: There were no significant changes of systemic parameters, median subcutaneous pO 2 values, median intratumoral pO 2 values, and the fractions of hypoxic pO 2 values ≤ 5 mm Hg in the tumor upon administration of spinal anesthesia. The variability of measured pO 2 values increased during spinal anesthesia, although substantial changes in the oxygenation status were only seen in individual cases (n = 2). Conclusion: This study shows for the first time that the oxygenation status of cervical carcinomas, in general, is not influenced by spinal anesthesia prior to application of brachytherapy. To conclude, the data presented suggest that reliable pO 2 measurements can be performed under spinal anesthesia. At the same time, since no substantial changes in tumor oxygenation were observed, spinal anesthesia should not affect the O 2 -related efficacy of high-dose-rate brachytherapy. (orig.)

  17. Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Cui Y

    2016-11-01

    Full Text Available Yanfen Cui,1,* Caiyuan Zhang,1,* Ran Luo,1 Huanhuan Liu,1 Zhongyang Zhang,1 Tianyong Xu,2 Yong Zhang,2 Dengbin Wang11Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 2MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: Arginine-glycine-aspartic acid (RGD-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA-coated ultrasmall superparamagnetic iron oxide (USPIO (referred to as RGD-PAA-USPIO in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC xenograft model by magnetic resonance imaging (MRI.Materials and methods: The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group.Results: The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05.Conclusion: This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in

  18. MicroRNA-30e Functions as a Tumor Suppressor in Cervical Carcinoma Cells through Targeting GALNT7

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    Huijuan Wu

    2017-12-01

    Full Text Available Cervical cancer is the third most common cancer in women worldwide. However, the underlying mechanism of occurrence and development of cervical cancer is obscure. In this study, we observed that miR-30e was downregulated in clinical cervical cancer tissues and cervical cancer cells. Next, overexpression of miR-30e reduced the cervical cancer cell growth through MTT, colony formation, EdU, and Transwell assay in SiHa and Caski cells. Subsequently, UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7 was identified as a potential miR-30e target by bioinformatics analysis. Moreover, we showed that miR-30e was able to bind to the 3′UTR of GALNT7 by luciferase reporter assay. In addition, the mRNA and protein levels of GALNT7 in cervical cancer cells were downregulated by miR-30e. And we validated that downregulation of GALNT7 repressed the proliferation of SiHa and Caski cells by MTT, colony formation, and Transwell assay. We identified that the restoration of GALNT7 expression was able to counteract the effect of miR-30e on cell proliferation of cervical cancer cells. Furthermore, we found that the expression levels of GALNT7 were frequently upregulated and negatively correlative to those of miR-30e in cervical cancer tissues. In addition, we validated that restoration of GALNT7 rescued the miR-30e–suppressed growth of cervical cancer xenografts in vivo. In conclusion, the current results suggest that miR-30e may function as tumor suppressors in cervical cancer through downregulation of GALNT7. Both miR-30e and its novel target, GALNT7, may play an important role in the process of cervical cancer.

  19. Which Patients With Cervical Squamous Cell Carcinoma Might Benefit From Neoadjuvant Chemotherapy?

    Science.gov (United States)

    Mahmoud, Omar; Einstein, Mark H

    2018-06-01

    The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 55-year-old postmenopausal woman, gravida 5 para 5, with past medical history significant for hypertension, presented to the emergency department with profuse vaginal bleeding and a hemoglobin level of 9 g/dL. The biopsy from an irregular 6-cm cervical mass was consistent with moderately differentiated cervical squamous cell carcinoma. The physical examination did not reveal vaginal or parametrial extension of the tumor. Pelvic magnetic resonance imaging disclosed the known carcinoma, as well as a 9.2 × 7.7 × 6.7 cm anterior uterine fibroid (Fig 1). A staging positron emission tomography scan was negative for metastatic disease. After blood transfusion and vaginal packing, the patient was referred to discuss the immediate management of her newly diagnosed bleeding bulky cervical cancer. In the absence of parametrial or vaginal extension and in the absence of lymph node metastasis (both on clinical examination and imaging), she was classified as having International Federation of Gynecology and Obstetrics stage IB2 disease.

  20. Preliminary comparative proteomics study of cervical carcinoma tissues with different sensitivity to concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    Zhu Hong; Liao Yuping; Zeng Liang; Xiao Zhiqiang

    2008-01-01

    Objective: To investigate the proteomics differences between the high-sensitivity(HS) and the low-sensitivity(LS) groups of cervical carcinoma treated by concurrent chemoradiotherapy, and to confirm the sensitivity associated proteins in intermediate stage and advanced cervical carcinoma. Methods: Fresh carcinoma tissues were collected from 10 untreated cervical carcinoma patients. According to the response to concurrent chemoradiotherapy, the tissues were classified into HS group and LS group. In the first part of our experiment, protein separation was performed using two-dimensional gel electrophoresis (2-DE) with Amersham 18 cm linear pH 3-10 immobilized pH gradient(IPG) strips. The images of the gels were analyzed by PD-quest 7.0 software to find the differentially expressed protein-spots in each group. Then the differentially expressed protein-spots were incised from the gels and digested by trypsin. The peptide mass fingerprintings (PMF) was acquired by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The proteins were identified by data searched in the Mascot-database. Two differentially expressed proteins were assayed by western blot and immunohistochemical methods. Results: Most of the gels were clear and successfully analyzed by PD-quest 7.0 software. Most of the protein-spots concentrated on the area of 20-100 KDa(Mw) and pH4-8. The average number of the protein-spots was 781 ± 74 in HS group and 766 ± 52 in LS group. The match rate was 87.6% between the two groups. Eight proteins highly in HS group but lowly expressed in LS group included hemoglobin subunit beta, caspase-14 precursor, calmodulindike, S100-A9 protein(MRP-14), galectin-7, HSKERC4, keratin 19 and actin. Ten proteins highly in LS group but lowly expression in HS group included anti HBs antibody light-chain Fab, lamin-B1, WARS protein, flavin reductase, glutamate dehydrogenase 1, nuclear matrix protein 238, retinal dehydrogenase 1, AF165172

  1. Radiation induced cell death in cervical squamous cell carcinoma. An immunohistochemical and ultrastructural study

    International Nuclear Information System (INIS)

    Atari, Eio; Toda, Takayoshi; Sadi, A.M.; Egawa, Haruhiko; Moromizato, Hidehiko; Mamadi, T.; Kiyuna, Masaya

    1998-01-01

    To study the process of cell death in cervical squamous cell carcinoma (SCC) after radiation, an ultrastructural and immunohistochemical study was performed. Paraffin-embedded tissue blocks of biopsy samples pre- and post-radiation stage III SCC (n=15) were collected. Irradiation caused varying ultrastructural changes including nuclear and cytoplasmic disorganization suggesting cell necrosis. Immunohistochemically, the pre-radiation specimens showed no positive reaction for tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-receptor (TNF-γ) or Fas. C-fos, p53 and bcl-2 showed positive reactions in only a few non-irradiated specimens. All of the irradiated specimens showed a positive reaction for TNF-α, and variable positive reactions were observed for TNF-γ, Fas, p53, c-fos and bcl-2. These results suggest that TNF-α, TNF-γ, and c-fos are responsible for radiation induced cell death in cervical SCC. (author)

  2. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

    Science.gov (United States)

    Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

    2016-06-01

    Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

  3. Dosimetric analysis at ICRU reference points in HDR-brachytherapy of cervical carcinoma.

    Science.gov (United States)

    Eich, H T; Haverkamp, U; Micke, O; Prott, F J; Müller, R P

    2000-01-01

    In vivo dosimetry in bladder and rectum as well as determining doses on suggested reference points following the ICRU report 38 contribute to quality assurance in HDR-brachytherapy of cervical carcinoma, especially to minimize side effects. In order to gain information regarding the radiation exposure at ICRU reference points in rectum, bladder, ureter and regional lymph nodes those were calculated (digitalisation) by means of orthogonal radiographs of 11 applications in patients with cervical carcinoma, who received primary radiotherapy. In addition, the doses at the ICRU rectum reference point was compared to the results of in vivo measurements in the rectum. The in vivo measurements were by factor 1.5 below the doses determined for the ICRU rectum reference point (4.05 +/- 0.68 Gy versus 6.11 +/- 1.63 Gy). Reasons for this were: calibration errors, non-orthogonal radiographs, movement of applicator and probe in the time span between X-ray and application, missing connection of probe and anterior rectal wall. The standard deviation of calculations at ICRU reference points was on average +/- 30%. Possible reasons for the relatively large standard deviation were difficulties in defining the points, identifying them on radiographs and the different locations of the applicators. Although 3 D CT, US or MR based treatment planning using dose volume histogram analysis is more and more established, this simple procedure of marking and digitising the ICRU reference points lengthened treatment planning only by 5 to 10 minutes. The advantages of in vivo dosimetry are easy practicability and the possibility to determine rectum doses during radiation. The advantages of computer-aided planning at ICRU reference points are that calculations are available before radiation and that they can still be taken into account for treatment planning. Both methods should be applied in HDR-brachytherapy of cervical carcinoma.

  4. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Science.gov (United States)

    Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

    2010-01-01

    OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

  5. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Directory of Open Access Journals (Sweden)

    Filomena M Carvalho

    2010-01-01

    Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

  6. The Prevalence and pattern of HPV-16 immunostaining in uterine cervical carcinomas in Ethiopian women: a pilot study

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    Mona M Rashed

    2011-03-01

    Full Text Available INTRODUCTION: Cancer of the cervix uteri is the second most common cancer among women worldwide. The association of human papillomavirus (HPV infection with cervical carcinogenesis is well documented. This is a pilot study aiming to studying the prevalence and the pattern of Human Papilloma Virus Type 16 (HPV16 by immunostaining in the tissues of cervical carcinomas of Ethiopian women. METHODS: 20 specimens of uterine cervical carcinomas were studied histopathologically and immunohistochemically for HPV16. RESULTS: Histologically the specimens were classified as: Ten cases were Non Keratinized Squamous cell carcinoma (NKSCC, six cases were Keratinized Squamous Cell Carcinoma (KSCC and four cases were Adenocarcinoma (ADC. Immunohistochemistry study showed positivity in eleven cases (55%; seven cases (35% were non-keratinized squamous cell carcinoma; three cases (15% were keratinized squamous cell carcinoma and one case (5% belonged to the adenocarcinomas. CONCLUSION: This study reveals a significant detection of HPV in Ethiopian women by the use of advanced techniques such as Immunohistochemistry (IHC. The data of this study suggested that the marked expression of the HPV 16 was in the less differentiated uterine cervix carcinomas

  7. Antitumour and antiangiogenic activities of [Pt(O,O'-acac)(γ-acac)(DMS)] in a xenograft model of human renal cell carcinoma.

    Science.gov (United States)

    Muscella, A; Vetrugno, C; Biagioni, F; Calabriso, N; Calierno, M T; Fornai, F; De Pascali, S A; Marsigliante, S; Fanizzi, F P

    2016-09-01

    It is thought that the mechanism of action of anticancer chemotherapeutic agents is mainly due to a direct inhibition of tumour cell proliferation. In tumour specimens, the endothelial cell proliferation rate increases, suggesting that the therapeutic effects of anticancer agents could also be attributed to inhibition of tumour angiogenesis. Hence, we investigated the potential effects of [Pt(O,O'-acac)(γ-acac)(DMS)] ([Pt(DMS)]), a new platinum drug for non-genomic targets, on human renal carcinoma and compared them with those of the well-established anticancer drug, cisplatin. Tumour growth, tumour cell proliferation and microvessel density were investigated in a xenograft model of renal cell carcinoma, developed by injecting Caki-1 cells into BALB/c nude mice. The antiangiogenic potential of compounds was also investigated using HUVECs. Treatment of the Caki-1 cells with cisplatin or [Pt(DMS)] resulted in a dose-dependent inhibition of cell survival, but the cytotoxicity of [Pt(DMS)] was approximately fivefold greater than that of cisplatin. [Pt(DMS)] was much more effective than cisplatin at inhibiting tumour growth, proliferation and angiogenesis in vivo, as well as migration, tube formation and MMP1, MMP2 and MMP9 secretion of endothelial cells in vitro. Whereas, cisplatin exerted a greater cytotoxic effect on HUVECs, but did not affect tube formation or the migration of endothelial cells. In addition, treatment of the xenograft mice with [Pt(DMS)] decreased VEGF, MMP1 and MMP2 expressions in tumours. The antiangiogenic and antitumour activities of [Pt(DMS)] provide a solid starting point for its validation as a suitable candidate for further pharmacological testing. © 2016 The British Pharmacological Society.

  8. Antitumour and antiangiogenic activities of [Pt(O,O′‐acac)(γ‐acac)(DMS)] in a xenograft model of human renal cell carcinoma

    Science.gov (United States)

    Vetrugno, C; Biagioni, F; Calabriso, N; Calierno, M T; Fornai, F; De Pascali, S A; Marsigliante, S; Fanizzi, F P

    2016-01-01

    Background and Purpose It is thought that the mechanism of action of anticancer chemotherapeutic agents is mainly due to a direct inhibition of tumour cell proliferation. In tumour specimens, the endothelial cell proliferation rate increases, suggesting that the therapeutic effects of anticancer agents could also be attributed to inhibition of tumour angiogenesis. Hence, we investigated the potential effects of [Pt(O,O′‐acac)(γ‐acac)(DMS)] ([Pt(DMS)]), a new platinum drug for non‐genomic targets, on human renal carcinoma and compared them with those of the well‐established anticancer drug, cisplatin. Experimental Approach Tumour growth, tumour cell proliferation and microvessel density were investigated in a xenograft model of renal cell carcinoma, developed by injecting Caki‐1 cells into BALB/c nude mice. The antiangiogenic potential of compounds was also investigated using HUVECs. Key Results Treatment of the Caki‐1 cells with cisplatin or [Pt(DMS)] resulted in a dose‐dependent inhibition of cell survival, but the cytotoxicity of [Pt(DMS)] was approximately fivefold greater than that of cisplatin. [Pt(DMS)] was much more effective than cisplatin at inhibiting tumour growth, proliferation and angiogenesis in vivo, as well as migration, tube formation and MMP1, MMP2 and MMP9 secretion of endothelial cells in vitro. Whereas, cisplatin exerted a greater cytotoxic effect on HUVECs, but did not affect tube formation or the migration of endothelial cells. In addition, treatment of the xenograft mice with [Pt(DMS)] decreased VEGF, MMP1 and MMP2 expressions in tumours. Conclusions and Implications The antiangiogenic and antitumour activities of [Pt(DMS)] provide a solid starting point for its validation as a suitable candidate for further pharmacological testing. PMID:27351124

  9. Integration of functional and morphological MR data for preoperative 3D visualisation of tumours. Cervical carcinoma

    International Nuclear Information System (INIS)

    Evers, H.; Meinzer, H.P.; Hawighorst, H.; Kaick, G. van; Knapstein, P.G.

    1998-01-01

    Purpose: The goal of this exemplary study was to integrate morphological and functional MRI to establish computer-based, preoperative therapy planning for tumors, instancing cervical carcinoma. Results: Segmentation of organs and vessels as well as tissue differentiation yielded a morphological visualisation of anatomical structures that were overlaid with pharmacokinetic parameters derived from dynamic MRI, subsequently. Thereby, three-dimensional, arbitrary views on the functional data were displayed. Conclusions: Image analysis and visualisation of the acquired MR data establishes both a morphologic and functional evaluation of suspect lesions and adjacent organs. By integrating morphologic and functional MRI additional information can be gathered that possibly impinge on preoperative planning. (orig./AJ) [de

  10. Sexual function after surgical and radiation therapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Seibel, M.; Freeman, M.G.; Graves, W.L.

    1982-01-01

    One hundred women treated for carcinoma of the cervix were interviewed more than one year later to establish the effects of radiation or surgical therapy on sexual function. Forty-three had received irradiation, 44 nonradical surgery, six combined surgery and irradiation, and seven radical surgery. The irradiation and nonradical surgery groups were each further subdivided into subgroups of patients aged 30 to 49 for age-controlled comparison. Patients in the irradiation group had statistically significant decreases in sexual enjoyment, ability to attain orgasm, coital opportunity, frequency of intercourse, and coital desire. The group who had nonradical surgical procedures had no significant change in sexual function after treatment. Similar results were found in both age-controlled subgroups, eliminating age as a major etiologic factor. Marked vaginal alterations were recorded in the majority of irradiated patients, but were not present among the groups treated with nonradical surgery. The vaginal changes alone could not be held accountable for the significant decrease in sexual function among women who received pelvic irradiation. The origin of decreased sexual desire after radiation therapy is complex, and not yet completely understood. We propose therapeutic programs to help women deal with the emotional and physical consequences of pelvic irradiation

  11. Sexual function after surgical and radiation therapy for cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Seibel, M. (Beth Israel Hospital, Boston, MA); Freeman, M.G.; Graves, W.L.

    1982-10-01

    One hundred women treated for carcinoma of the cervix were interviewed more than one year later to establish the effects of radiation or surgical therapy on sexual function. Forty-three had received irradiation, 44 nonradical surgery, six combined surgery and irradiation, and seven radical surgery. The irradiation and nonradical surgery groups were each further subdivided into subgroups of patients aged 30 to 49 for age-controlled comparison. Patients in the irradiation group had statistically significant decreases in sexual enjoyment, ability to attain orgasm, coital opportunity, frequency of intercourse, and coital desire. The group who had nonradical surgical procedures had no significant change in sexual function after treatment. Similar results were found in both age-controlled subgroups, eliminating age as a major etiologic factor. Marked vaginal alterations were recorded in the majority of irradiated patients, but were not present among the groups treated with nonradical surgery. The vaginal changes alone could not be held accountable for the significant decrease in sexual function among women who received pelvic irradiation. The origin of decreased sexual desire after radiation therapy is complex, and not yet completely understood. We propose therapeutic programs to help women deal with the emotional and physical consequences of pelvic irradiation.

  12. Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

    Science.gov (United States)

    Annunziata, Clorinda; Pezzuto, Francesca; Greggi, Stefano; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2018-03-31

    Two recurrent mutations (-124 G > A and -146 G > A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position -124 or -146. TERT promoter was mutated at nucleotide -146 (G > A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (-124G > A or -146G > A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression. © 2018 UICC.

  13. Radium needles implant in the treatment of extensive vaginal involvement from cervical carcinoma

    International Nuclear Information System (INIS)

    Sewchand, W.; Prempree, T.; Patanaphan, V.; Carbone, D.; Salazar, O.M.

    1984-01-01

    An appraisal of the dosimetry of a modified brachytherapy approach is presented for improving the local control of extensive vaginal involvement from carcinoma of the cervix. This approach incorporates radium needles implant to the vaginal disease in conjunction with the usual routine intracavitary radium application. The aim of the interstitial implant is specifically to supplement the dose to the vaginal disease from the intracavitary application. Our procedure for accomplishing this boost in the dose to the vagina depends on the location, extent and thickness of the vaginal lesion following external beam irradiation of the whole pelvis. An increase of greater than 50% in the dose to the vaginal disease is gained by this combination intracavitary/implant approach which has been used in a variety of cases covering virtually all pertinent stages of cervical carcinoma. Discussion of the dosimetry of example cases is presented to demonstrate the value of combining interstitial and intracavitary therapy for this specific clinical application. (orig.)

  14. Cervicitis

    Science.gov (United States)

    ... that does not go away: discharge may be gray, white or yellow in color Painful sexual intercourse ... Names Cervical inflammation; Inflammation - cervix Images Female reproductive anatomy Cervicitis Uterus References Eckert LO, Lentz GM. Infections ...

  15. Clinical and survival impact of FDG PET in patients with suspicion of recurrent cervical carcinoma

    International Nuclear Information System (INIS)

    Pallardy, Amandine; Testard, Aude; Resche, Isabelle; Bridji, Boumediene; Bodet-Milin, Caroline; Oudoux, Aurore; Ansquer, Catherine; Campion, Loic; Bourbouloux, Emmanuelle; Sagan, Christine; Kraeber-Bodere, Francoise; Rousseau, Caroline

    2010-01-01

    The aim of this retrospective study was to evaluate the contribution of 18 F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival. A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard. The final diagnosis was established pathologically (n=25) or by median clinical follow-up for 48 months after the PET (n=15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (>3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings with ≤1 focus for which the median survival was not attained (p=0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (>3 foci) was the most significant factor (p<0.03) for death from cervical cancer. FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome. (orig.)

  16. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    International Nuclear Information System (INIS)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O.; Knebel Doeberitz, M. von

    1998-01-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [de

  17. Late urologic morbidity in 177 consecutive patients after radiotherapy for cervical carcinoma: a longitudinal study

    International Nuclear Information System (INIS)

    Lajer, Henrik; Thranov, Ingrid R.; Skovgaard, Lene T.; Engelholm, Svend Aa

    2002-01-01

    Purpose: To provide longitudinal data on urologic morbidity after radiotherapy and brachytherapy for cervical carcinoma. Methods and Materials: Five-year longitudinal urologic morbidity data were recorded from 177 consecutive patients of median age 59 years (range: 22-86 years) with cervical carcinoma receiving radiotherapy with curative intent at the Copenhagen University Hospital, Denmark. FIGO stages (%) were as follows: Stage I (15), Stage II (30), Stage III (54), and Stage IV (1). Late morbidity was calculated as cumulative incidence based on actuarial estimates. Results: The 5-year cumulative incidence based on actuarial estimates of urologic morbidity Grades 1 + 2 + 3, Grades 2 + 3, and Grade 3 were 62%, 32%, and 5%, respectively. Frequencies of urologic morbidity in the 54 recurrence-free survivors at the end of follow-up indicated some reversibility in the case of Grades 1 and 2 morbidity. Conclusion: With the longitudinal design used in the present study, a rate of mild and moderate morbidity higher than that found in most of the previously reported literature was observed, giving cause for concern and underlining the importance of further longitudinal studies on this subject, specifically studies that relate to the background urologic morbidity in the female population, as well as to the fact that urologic morbidity might regress

  18. Radical surgery compared with intracavitary cesium followed by radical surgery in cervical carcinoma stage IB

    Energy Technology Data Exchange (ETDEWEB)

    Tinga, D.J.; Bouma, J.; Aalders, J.G. (Dept. of Obstetrics and Gynaecology, State Univ. Hospital, Groningen (Netherlands)); Hollema, H. (Dept. of Pathology, State Univ. Hospital, Groningen (Netherlands))

    1990-01-01

    Forty-nine patients aged {le} 45 years, with cervical carcinoma stage IB ({le} 3 cm) were treated with either primary radical surgery (n = 26), or intracavitary irradiation followed by radical surgery (n = 23). With primary surgery, ovarian function had been preserved in 15 of the 25 patients, who were alive and well. Seven of the primary surgery patients were irradiated postoperatively and 2 others with a central recurrence were cured by irradiation. One other patient, who was not irradiated postoperatively, had an intestinal metastasis and died of the disease. If any of the adverse prognostic factors (as reported in the literature) had been considered as an indication for postoperative irradiation, 17 patients instead of 7 would have been irradiated after primary radical surgery. In the comparable group of 23 patients treated by intracavitary irradiation and radical surgery (and in 4 cases postoperative irradiation as well) there was no recurrence. There was no significant statistical difference between the treatment results in the cesium + surgery group and those who underwent primary radical surgery. Young patients with early cervical carcinoma without prognostic indicators for postoperative irradiation can benefit from primary radical surgery, because their ovarian function can be preserved. (authors).

  19. Cytotoxic effect and radiation enhancement of artemisinin in uterine cervical carcinoma cell line HeLa

    International Nuclear Information System (INIS)

    Gong Xiaomei; Zhou Daoan; Cao Jianping; Fan Saijun; Zhu Wei

    2010-01-01

    Objective: To investigate cytotoxic and radiosensitizing effect of Artemisinin on cervical carcinoma cell line HeLa. Methods: In order to measure the optimized effective time, cytotoxic effect of Artemisinin on HeLa cell line was investigated with MTT assay. The radiosensitization effect of different doses and different treatment duration of Artemisinin on HeLa cell line were evaluated by MTT test, the SER is 1.17 and radiosensitizing effect was measured with multi-target single hit model through SER of HeLa cell. Cell cycles in different groups were calculated by flow cytometry. Results: The 50% inhibition concentration of Artemisinin interacted with HeLa cells for 24 h is 600.19 nmol/ml, and for 48 h is 160.71 nmol/ml. The HeLa cells'surival ratio is 93.51%, 91.87%, and 87.28% after adding Atemisinin of 110.69 nmol/ml and 1 Gy radiation exposure. There are three groups: the chemotherapy only group, the radiotherapy only group and the combination group. The result of the cell cycles showed that cells in G 2 /M period decreased in the combination group. Conclusion: Artemisinin has radiosensitization effect on cervical carcinoma HeLa cells, whichshows dose and time dependent. Artemisinin can inhibit the G 2 /M block by ionizing radiation. (authors)

  20. Radical surgery compared with intracavitary cesium followed by radical surgery in cervical carcinoma stage IB

    International Nuclear Information System (INIS)

    Tinga, D.J.; Bouma, J.; Aalders, J.G.; Hollema, H.

    1990-01-01

    Forty-nine patients aged ≤ 45 years, with cervical carcinoma stage IB (≤ 3 cm) were treated with either primary radical surgery (n = 26), or intracavitary irradiation followed by radical surgery (n = 23). With primary surgery, ovarian function had been preserved in 15 of the 25 patients, who were alive and well. Seven of the primary surgery patients were irradiated postoperatively and 2 others with a central recurrence were cured by irradiation. One other patient, who was not irradiated postoperatively, had an intestinal metastasis and died of the disease. If any of the adverse prognostic factors (as reported in the literature) had been considered as an indication for postoperative irradiation, 17 patients instead of 7 would have been irradiated after primary radical surgery. In the comparable group of 23 patients treated by intracavitary irradiation and radical surgery (and in 4 cases postoperative irradiation as well) there was no recurrence. There was no significant statistical difference between the treatment results in the cesium + surgery group and those who underwent primary radical surgery. Young patients with early cervical carcinoma without prognostic indicators for postoperative irradiation can benefit from primary radical surgery, because their ovarian function can be preserved. (authors)

  1. Clinical Significance of Plasma CEA Levels in the Patients with Cervical Carcinoma during Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Sung Beom; Kim, Joo Young; Choi, Myung Sun; Rha, Joong Yeol; Lee, Min Jae [Korea University College of Medicine, Seoul (Korea, Republic of)

    1991-12-15

    Carcinoembryonic antigen (CEA) has been studied in the field of gynecologic malignancy to determine whether it can be used as a tumor marker for early detection of recurrence or evaluation of therapeutic results. From January 1985 through December 1989, a total of 239 cervical cancer patients were entered for an analysis of plasma CEA level in the group with cervical cancer compared to the control group consisting of 65 normal healthy women and 18 women with benign gynecologic disease. Plasma CEA levels appear to be directly related with the tumor extension and as stages advance, the incidence of patients with abnormal plasma CEA levels is increased. Also, there seems to be a little higher incidence of abnormal CEA levels in patients with adenocarcinomas or adenosquamous carcinoma but not statistically significant because of small number of patients. When the patients developed recurrence, plasma CEA levels are markedly elevated in the majority, particularly in patients with hepatic metastases. In conclusion, serial plasma CEA checks could be used to detect recurrence during follow-up after treatment of cervical cancer.

  2. Pharmacological manipulation of radiation induced apoptosis in a cervical carcinoma cell line

    International Nuclear Information System (INIS)

    Kamradt, M.; Mohideen, N.; Krueger, E.; Sokolova, I.A.; Khodarev, N.N; Vaughan, A.T.M.

    1997-01-01

    Purpose: Radiotherapy is a curative option in the treatment of early stage cervical carcinoma and radioresistant tumors limit local control and survival. Therefore, it is important to understand mechanisms by which cells evade death after irradiation. Of these, the process of apoptosis offers a useful model system to study. Tumors of the cervix offer a unique opportunity in that most contain an HPV genome expressing the E6 and E7 gene products under the control of a glucocorticoid responsive promoter. The HPV E6 and E7 proteins target p53 and/or Rb, both of which are involved in cell cycle control and in the apoptotic process. It was previously determined that treatment with the corticosteroid dexamethasone increased transcription of E6 and E7 and decreased p53 protein levels which corresponded with increased radioresistance and decreased apoptosis in C4-1 cervical carcinoma cells. The goal of this study is to demonstrate pharmacological manipulation of apoptosis within an HPV +ve cervical cell line. Methods: The HPV 18 +ve and p53 wildtype human cervical cell line C4-1 was used in this study. Apoptosis was induced by exposure to 6 Gy of gamma radiation and the ability of cells to undergo apoptosis was determined by morphology and the ability to form internucleosomal fragments using a DNA laddering technique. Cells were exposed to 0.01 to 1 μM dexamethasone in the presence or absence of 1 μM Mifepristone (RU486), a steroid antagonist and analyzed using the DNA laddering assay. In addition, cells that were irradiated in the presence of dexamethasone and/or Mifepristone were collected and p53 protein levels determined by FACS analysis. Results: Apoptosis was observed at a low level in control cells and was increased by irradiation with 6 Gy as determined by DNA laddering and morphology. The presence of 0.01 to 1 μM dexamethasone reduced both the radiation induced DNA laddering and also that seen in control cells. Addition of 1 μM Mifepristone to dexamethasone

  3. ANTIBODIES TO HUMAN PAPILLOMAVIRUS TYPE-16 E7 RELATED TO CLINICOPATHOLOGICAL DATA IN PATIENTS WITH CERVICAL-CARCINOMA

    NARCIS (Netherlands)

    BAAY, MFD; DUK, JM; BURGER, MPM; WALBOOMERS, J; TERSCHEGGET, J; GROENIER, KH; DEBRUIJN, HWA; STOLZ, E; HERBRINK, P

    Aims-To investigate the correlation between antibodies to the transforming protein E7 of human papillomavirus (HPV) type 16 and clinicopathological indices in women with cervical squamous carcinoma. Methods-A synthetic peptide of the HPV type 16 E7 protein (amino acids 6 to 35) was used to screen

  4. When is bacterial vaginosis not bacterial vaginosis?--a case of cervical carcinoma presenting as recurrent vaginal anaerobic infection.

    OpenAIRE

    Hudson, M M; Tidy, J A; McCulloch, T A; Rogstad, K E

    1997-01-01

    Vaginal anaerobic infection is the most common cause of vaginal discharge in women. We present a case of recurrent vaginal anaerobic infection and cervical carcinoma and discuss the association of the two conditions. More frequent cytology/colposcopy may be indicated in women who give a history of recurrent or persistent vaginal anaerobic infection.

  5. Two cases of fatal necrosis of the lesser pelvis in patients treated with combined radiotherapy and hyperthermia for cervical carcinoma

    NARCIS (Netherlands)

    Wiggenraad, R.; Koning, C.; Westermann, C.; Jansen, C.; van der Zee, J.

    2005-01-01

    This study reports two cases of fatal necrosis of the lesser pelvis in patients with advanced cervical carcinoma, who had received combined radiotherapy and hyperthermia. The necrosis reached far from the high dose area, in one of the cases even outside the radiation portals. Both patients initially

  6. Human Papillomavirus Cervical Infection and Associated Risk Factors in a Region of Argentina With a High Incidence of Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    S. A. Tonon

    1999-01-01

    Full Text Available Objective: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer.

  7. Role of percutaneous nephrostomy in advanced cervical carcinoma with obstructive uropathy: A case series

    Directory of Open Access Journals (Sweden)

    Kamlesh Mishra

    2009-01-01

    Full Text Available Aims and Objective: Over 70% of the cases present in advanced stages of the disease and are associated with poor prognosis and high mortality rates. In many of them, it is difficult to offer definitive treatment as they present in uremia due to associated obstructive uropathy. There are no clear-cut guidelines for performing percutaneous nephrostomy (PCN in patients of advanced cervical cancer. The results are unpredictable in terms of benefits achieved in these cases. Thus, we evaluated our experiences with PCN in the management of cervical cancer patients presenting with obstructive uropathy. Material and Methods: 15 patients of cervical cancer with obstructive uropathy and deranged renal functions were retrospectively evaluated for the role of PCN in their management Results: PCN was done in 15 patients of advanced cervical cancer. The mean age of patients was 44.5 years. Twelve (80% patients presented primarily with advanced cervical carcinoma and obstructive uropathy. Three (20% were already treated. Symptomatic improvement and significant fall of mean serum creatinine value from 7.5 mg% to 0.9 mg% over a period of 1-3 weeks was noted post PCN. Out of 12 patient with primary untreated advanced disease, curative treatment was possible in 3, palliative radiotherapy/chemo-therapy in 7 and only symptomatic treatment in 2 cases, after obstructive uropathy was managed with PCN insertion. Out of 3 already treated patients, 2 were disease free after curative radiotherapy/surgery. PCN was done to prevent permanent kidney damage in them. One patient was defaulter of curative radiotherapy. She had progressive residual disease. Complications like hemorrhage (20%, infection (26%, reinsertion for dislodgment/misplacement (53%, percutaneous leak or perinephric leak (20%, blockage of PCN (33% were noticed. Conclusion: In spite of inherent, albeit manageable complications, PCN is a simple and safe technique. One of the major benefits observed was

  8. A study of bone metastasis of cervical carcinoma by bone scintigraphy

    International Nuclear Information System (INIS)

    Okamura, Shinsuke; Okamoto, Yoshiaki; Maeda, Takayoshi; Sano, Takashi; Ueki, Minoru; Sugimoto, Osamu; Sakata, Tsunehiko; Yamasaki, Kouichi; Akagi, Hiroaki

    1985-01-01

    In carrying out bone scintigraphy in 224 cases over the 5 years from June, 1978 to May, 1983 as a part of the post-treatment management of cervical carcinoma. Bone metastases were seen in 12.5% (28 cases) of the subjects, about 6% of the total post-treatment cases of cervical carcinoma in the corresponding period (466 cases). Bone metastases were seen in 9.3% (16/172) of post-operative cases, compared with 23.1% (12/52) of non-operative cases. Bone metastases were not seen in clinical stages Ia through IIa (49 cases) but were seen in IIb or higher stages. Bone metastasis rates by histological type, according to WHO classification, were 12.8% (26/203) in squamous cell carcinoma, 5.9% (1/17) in adenocarcinoma, and 25% (1/4) in adenosquamous carcinoma. Among the squamous cell carcinoma cases, small cell non-keratinizing type had the highest bone metastasis rate (p<0.05). Of 172 post-operative cases, 20.8% (11/53) of those with lymphnode metastasis exhibited bone metastasis, higher than the 4.2% (5/119) in cases without lymphnode metastasis. As to CPL classification, bone metastasis was seen more often in L type (18.8%) than C(0.0%) or P types (6.6%). Our risk classification of 168 cases demonstrated that bone metastasis was not seen in risk I group (74 cases), but was seen in 6.7% (1/17) of risk II group and in 19.0% (15/79) of risk III group. Twenty-eight cases with bone metastasis included 11 cases with local recurrence, 8 with pulmonary metastases, 4 with hepatic metastases and 4 with Virchow's lymphnode metastases. The 28 bone metastasis cases included 10 cases with multiple bone metastases and 5 with only a single bone metastasis. Most bone metastases were seen in the lumbar vertebrae and the pelvic bone. Post-operative cases had more distant metastases than non-operative cases. On diagnosis of bone metastases and 17 of the 28 patients had pain, 6 of the remaining 11 patients developing pain thereafter. (J.P.N.)

  9. Programmed cell death as a prognostic indicator for radiation therapy in cervical carcinoma patients: A pilot study

    Directory of Open Access Journals (Sweden)

    Bhosle S

    2005-01-01

    Full Text Available Purpose: In clinical practice, radiation therapy often fails in cervical carcinoma stage IIIB and there is a need to develop a predictive assay for prognosis of radiation treatment outcome in cancer patient. We have attempted to evaluate the relevance of changes in Membrane Fluidity (MF and associated apoptotic cell death in cervical cancer cells after first fractionated dose of radiation therapy to treatment outcome of stage IIIB cervical carcinoma patients. Materials and Methods: Biopsies of 15 patients with histologically proven cervix cancer were collected from the patients before and 24 h after first fractionated radiation dose of 2 grays (Gy. Cell suspension made in Dulbecco′s Modified Eagle′s Medium (DMEM were used for further investigations and cell suspension of cervix cancer patient were used to measure MF by fluorescence polarization method and apoptotic index (AI was determined by Tdt dUTP Nucleotide End Labeling (TUNEL assay. Results: A substantial increase in MF and AI was observed in cervical cancer cells irradiated ex vivo . A significant correlation ( P < 0.001 was found between the changes in AI after first fractionated dose of radiotherapy and treatment outcome of patients. No significant correlation ( P > 0.1 was detected between changes in MF and treatment outcome of patients. Conclusion: Preliminary results showed significant change in MF and a marked increase in percentage apoptosis of cervix cancer cells irradiated ex vivo . The changes in AI after first fractionated dose of radiotherapy in cervical carcinoma patients may provide a predictor of prognosis for radiotherapy in uterine cervical carcinoma patients.

  10. Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma.

    Science.gov (United States)

    Itai, Shunsuke; Ohishi, Tomokazu; Kaneko, Mika K; Yamada, Shinji; Abe, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Ohba, Shun-Ichi; Nishioka, Yasuhiko; Kawada, Manabu; Harada, Hiroyuki; Kato, Yukinari

    2018-04-27

    Podocalyxin (PODXL) overexpression is associated with progression, metastasis, and poor outcomes in cancers. We recently produced the novel anti-PODXL monoclonal antibody (mAb) PcMab-47 (IgG 1 , kappa). Herein, we engineered PcMab-47 into 47-mG 2a , a mouse IgG 2a -type mAb, to add antibody-dependent cellular cytotoxicity (ADCC). We further developed 47-mG 2a -f, a core fucose-deficient type of 47-mG 2a to augment its ADCC. Immunohistochemical analysis of oral cancer tissues using PcMab-47 and 47-mG 2a revealed that the latter stained oral squamous cell carcinoma (OSCC) cells in a cytoplasmic pattern at a much lower concentration. PcMab-47 and 47-mG 2a detected PODXL in 163/201 (81.1%) and in 197/201 (98.0%) OSCC samples, respectively. 47-mG 2a -f also detected PODXL in OSCCs at a similar frequency as 47-mG 2a . In vitro analysis revealed that both 47-mG 2a and 47-mG 2a -f exhibited strong complement-dependent cytotoxicity (CDC) against CHO/hPODXL cells. In contrast, 47-mG 2a -f exhibited much stronger ADCC than 47-mG 2a against OSCC cells, indicating that ADCC and CDC of those anti-PODXL mAbs depend on target cells. In vivo analysis revealed that both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in CHO/hPODXL xenograft models at a dose of 100 μg or 500 μg/mouse/week administered twice. 47-mG 2a -f, but not 47-mG 2a , exerted antitumor activity in SAS and HSC-2 xenograft models at a dose of 100 μg/mouse/week administered three times. Although both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in HSC-2 xenograft models at a dose of 500 μg/mouse/week administered twice, 47-mG 2a -f also showed higher antitumor activity than 47-mG 2a . These results suggested that a core fucose-deficient anti-PODXL mAb could be useful for antibody-based therapy against PODXL-expressing OSCCs.

  11. HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case-control study

    Directory of Open Access Journals (Sweden)

    Kleter Bernhard

    2011-06-01

    Full Text Available Abstract Background While the association of human papillomavirus (HPV with cervical cancer is well established, the influence of HIV on the risk of this disease in sub-Saharan Africa remains unclear. To assess the risk of invasive cervical carcinoma (ICC associated with HIV and HPV types, a hospital-based case-control study was performed between September 2004 and December 2006 in Kampala, Uganda. Incident cases of histologically-confirmed ICC (N=316 and control women (N=314, who were visitors or care-takers of ICC cases in the hospital, were recruited. Blood samples were obtained for HIV serology and CD4 count, as well as cervical samples for HPV testing. HPV DNA detection and genotyping was performed using the SPF10/DEIA/LiPA25 technique which detects all mucosal HPV types by DEIA and identifies 25 HPV genotypes by LiPA version 1. Samples that tested positive but could not be genotyped were designated HPVX. Odds ratios (OR and 95% confidence intervals (CI were calculated by logistic regression, adjusting for possible confounding factors. Results For both squamous cell carcinoma (SCC and adenocarcinoma of the cervix, statistically significantly increased ORs were found among women infected with HPV, in particular single HPV infections, infections with HPV16-related types and high-risk HPV types, in particular HPV16, 18 and 45. For other HPV types the ORs for both SCC and adenocarcinoma were not statistically significantly elevated. HIV infection and CD4 count were not associated with SCC or adenocarcinoma risk in our study population. Among women infected with high-risk HPV types, no association between HIV and SCC emerged. However, an inverse association with adenocarcinoma was observed, while decrease in CD4 count was not associated with ICC risk. Conclusions The ORs for SCC and adenocarcinoma were increased in women infected with HPV, in particular single HPV infections, infections with HPV16- and 18-related types, and high-risk HPV types

  12. Squamous cell carcinoma of the rectum 21 years after radiotherapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Leung, Kevin K; Madan, Anand; Heitzman, Joseph

    2009-01-01

    Squamous cell carcinoma (SCC) of the rectum is an extremely rare malignancy, accounting for 0.1-0.2% of rectal malignancies. It is associated with ulcerative colitis, prior radiation, schistosomiasis, ovarian cancer, endometrial cancer, human papilloma virus, colocutaneous fistulas and colonic duplication. Prior reported cases of SCC of the rectum have involved treatment with brachytherapy and external beam radiation. This case is particularly interesting because of the remote exposure of radiation (21 years previously) and the subsequent development of SCC of the rectum. Although extremely rare, SCC of the rectum can occur decades after radiation exposure. (author)

  13. Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A longitudinal study

    DEFF Research Database (Denmark)

    Jensen, Pernille T; Groenvold, Mogens; Klee, Marianne C

    2004-01-01

    with an age-matched control group from the general population. RESULTS: Compared with control women, patients experienced severe orgasmic problems and uncomfortable sexual intercourse due to a reduced vaginal size during the first 6 months after RH, severe dyspareunia during the first 3 months, and sexual......BACKGROUND: Limited knowledge exists concerning the impact of radical hysterectomy (RH) alone on the sexual function of patients with early-stage cervical carcinoma. The authors investigated the longitudinal course of self-reported sexual function after RH. METHODS: The current study was comprised...... dissatisfaction during the 5 weeks after RH. A persistent lack of sexual interest and lubrication were reported throughout the first 2 years after RH. Long-term lack of sexual interest and insufficient vaginal lubrication were confirmed by the patient's self-reported changes 12 months after RH compared...

  14. Feasibility study of an alternating schedule of radiotherapy and chemotherapy in advanced uterine cervical carcinoma

    International Nuclear Information System (INIS)

    Haie, C.; Chassagne, D.; Gerbaulet, A.; George, M.; Pejovic, M.H.; Horiot, J.C.; Fenton, J.; Le Floch, O.; Heron, J.F.

    1988-01-01

    36 patients with advanced cervical carcinoma stage III (24 patients) and stage IV (12 patients) entered a feasibility study of a radiotherapy and chemotherapy combination. The first three chemotherapy courses consisted of cis-platinum alone and were interdigitated with radiotherapy. Six more courses composed of an association of cis-platinum and cyclophosphamide were given after the completion of radiotherapy. Radiotherapy was delivered in two courses of 25 Gy separated by a gap of 2 weeks. The overall 4-year survival rate, cumulative loco-regional failure rate, and cumulative meatstasis rate were respectively 44%, 56% and 30% in stage III and 28%, 83% and 74% in stage IV. The incidence of immediate and late complications was low: no patient had her radiotherapy stopped because of an intolerance and two patients had their chemotherapy stopped because of an haematological intolerance. Only one patient presented a severe late clinical complication (small bowel injury). 29 refs.; 2 figs.; 4 tabs

  15. Radiation-induced femoral neck fracture in patients cured of cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lukowska, K; Zomer-Drozda, J; Kielbinska, S [Instytut Onkologii, Warsaw (Poland)

    1976-01-01

    In the years 1948-1967 8275 patients with cervical carcinoma in various grades of progression were treated at the Institute of Oncology in Warsaw by radiotherapy from external fields. Five-year survival without signs of recurrence was obtained in 4204 cases, 3863 of them were irradiated from external fields with X-rays under conventional conditions, while 341 received Co/sup 60/ radiotherapy. In 43 patients treated with X-rays and radium and regarded as cured radiological evidence of femoral neck fracture was obtained. These patients account for 1.1% of all cured patients. In the group treated with Co/sup 60/ radiation in only 1 case femoral neck fracture was observed (0.3%). In the group of cured patients with femoral neck fracture the method of irradiation from external fields, the age, clinical course, radiological appearance of radiation-induced changes and the method of fracture management were analysed.

  16. Determination of the anatomic borders of the irradiation area for cervical and corporal carcinomas

    International Nuclear Information System (INIS)

    Moeller-Kuhlmann, G.

    1980-01-01

    Intention of the present study was to refer the silhouettes of the irradiation field to anatomically definite osseous structures. For this examination the caudal, cranial and the lateral borders were marked by different methods and their position with respect to the corresponding osseous structures was detected. For documenting the soft-tissue structures the following techniques could be applied: lymphography, hysterosalpingography, vaginal contrasting and computerized tomography. The evaluation of the obtained results showed that the dorsal silhouette ranges between the 4th and 5th lumbar vertebrae, that the lateral silhouette reaches the middle of the head of the femur and that the caudal one includes the obturator. The detection and definition of the target area for curative radiotherapy of corporal and cervical carcinomas can therefore renounce on the contrast representation of soft-tissue organs. On the contrary it is even possible to adjust the irradiation field with the therapy simulator under consideration of anatomically fixed osseous structures. (orig./MG) [de

  17. Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology.

    Science.gov (United States)

    Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang

    2016-02-02

    Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

  18. Nasopharyngeal Carcinoma with Cystic Cervical Metastasis Masquerading as Branchial Cleft Cyst: A Potential Pitfall in Diagnosis and Management.

    Science.gov (United States)

    Sai-Guan, Lum; Min-Han, Kong; Kah-Wai, Ngan; Mohamad-Yunus, Mohd-Razif

    2017-03-01

    Most metastatic lymph nodes from head and neck malignancy are solid. Cystic nodes are found in 33% - 61% of carcinomas arise from Waldeyer's ring, of which only 1.8% - 8% originate are from the nasopharynx. Some cystic cervical metastases were initially presumed to be branchial cleft cyst. This case report aims to highlight the unusual presentation of cystic cervical metastasis secondary to nasopharyngeal carcinoma in a young adult. The histopathology, radiological features and management strategy were discussed. A 36-year-old man presented with a solitary cystic cervical swelling, initially diagnosed as branchial cleft cyst. Fine needle aspiration yielded 18 ml of straw-coloured fluid. During cytological examination no atypical cells were observed. Computed tomography of the neck showed a heterogeneous mass with multiseptation medial to the sternocleidomastoid muscle. Histopathological examination of the mass, post excision, revealed a metastatic lymph node. A suspicious mucosal lesion at the nasopharynx was detected after repeated thorough head and neck examinations and the biopsy result confirmed undifferentiated nasopharyngeal carcinoma. Cystic cervical metastasis may occur in young patients under 40 years. The primary tumour may not be obvious during initial presentation because it mimicks benign branchial cleft cyst clinically. Retrospective review of the computed tomography images revealed features that were not characteristic of simple branchial cleft cyst. The inadequacy of assessment and interpretation had lead to the error in diagnosis and subsequent management. Metastatic head and neck lesion must be considered in a young adult with a cystic neck mass.

  19. Results of salvage radiotherapy after inadequate surgery in invasive cervical carcinoma patients: A retrospective analysis

    International Nuclear Information System (INIS)

    Saibishkumar, Elantholi P.; Patel, Firuza D.; Ghoshal, Sushmita; Kumar, Vinay; Karunanidhi, Gunaseelan; Sharma, Suresh C.

    2005-01-01

    Purpose: To evaluate the results of salvage radiotherapy (RT) after inadequate surgery in patients with invasive carcinoma of the cervix. Methods and Materials: Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at our center with external beam RT with or without intracavitary RT after having undergone total/subtotal hysterectomy at outside institutions. Results: The median follow-up was 34 months. The gap between surgery and RT was 23-198 days (median, 80). Clinically visible residual disease was present in 81 patients (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal hysterectomy in 23 patients (22%). The 5-year overall survival, disease-free survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%, respectively. On univariate analysis, older age, total hysterectomy, hemoglobin level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a shorter gap between surgery and RT, and the absence of, or a small volume of, residual disease favorably affected the outcome. The 5-year actuarial rate of late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum, 4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine. Conclusions: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. Factors such as the use of intracavitary RT, the correction of anemia, and a shorter gap between surgery and RT will enable postoperative RT to achieve acceptable results with minimal morbidity

  20. Medium dose rate brachytherapy for patients with cervical carcinoma; early result of a prospective study

    Directory of Open Access Journals (Sweden)

    Amouzegar Hashemi F

    2009-03-01

    Full Text Available "nBackground: Treatment of cervical carcinoma is routinely performed with Low Dose Rate (LDR brachytherapy, but Brachytherapy in our department is done with Medium Dose Rate (MDR due to the technical characteristics of the machine available here. Thus we decided to evaluate the results of this treatment in our department in a prospective study. "nMethods: Between March 2006 and July 2008, 140 patients with histologic diagnosis of cervical carcinoma referred to Tehran Cancer Institute; were treated with external beam radiotherapy (44-64 Gy to whole pelvis and MDR brachytherapy (8-30 Gy to Point A with a dose rate of 2.2±0.3 Gy/h. "nResults: 121 patients were followed up for a median time of 18 months (range: 9-39 m. There were 11%(6/54 local recurrence for surgery and adjuvant radiotherapy group; 25%(16/65 for radical radiotherapy group, and 19%(23/121 for all patients. Rectal and bladder complications incidence for all patients were 10%(12/121 and 13%(16/121 respectively. High grade complication was shown only in one patient in radical radiotherapy group. In this study 3-years disease free survival and overall survival were 73% and 92% respectively, and disease stage (p=0.007 and overall treatment time (p=0.05 were the significant factors affecting disease free survival. "nConclusions: Results of this series suggest that the use of external beam radiotherapy and MDR brachytherapy with about 20% dose reduction in comparison with LDR can be an acceptable technique with regard to local control and complications.

  1. Hyperthermia and PARP1-inhibition for sensitization of radiation and cisplatin treatment of cervical carcinoma cells

    International Nuclear Information System (INIS)

    Franken, Nicolaas; Oei, Arlene; Leeuwen, Caspar van; Stalpers, Lukas; Rodermond, Hans; Bel, Arjan; Kok, Petra; Crezee, Hans

    2014-01-01

    Ionizing radiation causes single and double strand breaks (SSBs and DSBs). DSBs are among the most critical DNA lesions and can be repaired via either non-homologous end joining (NHEJ) in which PARP1, Ku70 and DNA-PKcs are important, or homologous recombination (HR), where BRCA2 and Rad51 are essential. Hyperthermia disturbs HR by temporary inactivation of BRCA2. Cisplatin disrupts NHEJ and PARP1-inhibitor blocks Poly-(ADP-ribose)polymerase- 1, which is important in SSB repair, NHEJ and backup-NHEJ. Our goal was to investigate the additional effectiveness of hyperthermia and PARP1-inhibition on radiation and/or cisplatin treatment. Cervical carcinoma cells (SiHa) were treated at different temperature levels levels (41.0-43.0℃, PARP1-inhibitor (100 μM; NU1025), gamma-irradiation doses (0-8 Gy) or cisplatin (1'R for 1 h). Clonogenic assays were carried out to measure survival and γH2AX staining was used to visualize DSBs. To elucidate mechanisms of action expression levels of DNA repair proteins BRCA2 and DNA-PKcs were investigated after 42.0℃ (1 h) using western blot. Combined hyperthermia and radiation resulted in an increased number of γH2AX foci as compared to radiation alone. Hyperthermia treatment in combination with cisplatin and PARP1 inhibitor and with radiation and PARP1 inhibitor significantly decreased cell survival. Western blot demonstrated a decreased expression of BRCA2 protein at 30 min after hyperthermia treatment. Adding PARP1-inhibitor significantly improves the effectiveness of combined hyperthermia radiotherapy and combined hyperthermia-cisplatin treatment on cervical carcinoma cells. Hyperthermia affects DNA-DSB repair as is indicated by increased γH2AX foci numbers and decreased BRCA2 expression. (author)

  2. The presence of advanced lesions and associating risk factors for advanced cervical carcinoma in patients with atypical sguamous cells of undetermined significance.

    Science.gov (United States)

    Sun, L L; Chen, W; Fan, Y Y; Wang, M L; Wang, L N

    2015-01-01

    To characterize histopathological status, high-risk human papillomavirus (hr-HPV) infection status, and associated risk factors in patients with atypical squamous cells of undetermined significance (ASCUS). Cervical biopsies obtained from 130 ASCUS patients were subjected to histopathological examination and hr-HPV testing. Associations between advanced lesions and hr-HPV load or age were analyzed, and the confounding factors for high-grade cervical lesions were identified. Cervical biopsies from ASCUS patients had a wide range of pathological states, ranging from normal to invasive cervical carcinoma. High-risk HPV infection was significantly associated with advanced cervical lesions in ASCUS patients; hr-HPV infection and the number of gestations were risk factors for developing advanced cervical disease. A significant portion of ASCUS patients harbor advanced cervical lesions. The number of gestations and hr-HPV infection can increase the risk of developing advanced cervical lesions in ASCUS patients.

  3. Monocarboxylate Transporters 1 and 4 Are Associated with CD147 in Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    Céline Pinheiro

    2009-01-01

    Full Text Available Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.

  4. Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

    International Nuclear Information System (INIS)

    Ohara, Kiyoshi; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

    2006-01-01

    Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day -1 ) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day -1 (median, 0.021 day -1 ) and late-assessed radioresponse from 0.009 to 0.091 day -1 (median, 0.021 day -1 ), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R 2 = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness

  5. [Carcinoma of the uterine cervical canal. Staging and biometric assessment with magnetic resonance].

    Science.gov (United States)

    Fischetti, S G; Politi, G; Lomeo, E; Garozzo, G; Di Leo, S; Nuciforo, G

    1994-10-01

    In uterine cervical canal carcinoma, the current clinical FIGO criteria often fail not only to differentiate stage IA2 from stage IB but also to demonstrate possible parametrial involvement. Moreover, the analysis of tumor volume and of the depth of neoplastic stromal invasion is not very reliable. The authors investigated MR accuracy in the definition of such variables: to this purpose, 24 patients with histologically confirmed endocervical adenocarcinoma were submitted to MRI, which was performed with an 0.5-T superconductive magnet. Sagittal and oblique transverse or sometimes coronal SE images, oriented so as to be perpendicular to longitudinal cervical major axis were obtained with T2 weighting (TR 1800 ms, TE 25-90 ms). MR data were correlated with pathologic findings. MR accuracy in demonstrating parametrial involvement was 92%, its sensitivity was 86% and specificity 97%. Volumetric MR data showed a high correlation (r = 0.970) with those derived from pathologic findings. In 92% of cases stromal invasion exceeded 5 mm. MRI, thanks to its high accuracy, should be included in diagnostic pretreatment protocols, even though FIGO criteria do not require it yet, especially in the presence of an endocervical adenocarcinoma. Moreover, the accurate definition of tumor volume can allow less extensive surgery with the same survival rates and fewer complications, which are frequently observed after radical hysterectomy.

  6. Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1981-08-01

    Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2.

  7. Effects of HIF-1 and HIF2 on Growth and Metabolism of Clear-Cell Renal Cell Carcinoma 786-0 Xenografts

    Directory of Open Access Journals (Sweden)

    Swethajit Biswas

    2010-01-01

    Full Text Available In cultured clear-cell renal carcinoma (CCRCC 786-0 cells transfected with HIF1 (HIF-1+, HIF-2 (HIF-2+, or empty vector (EV, no significant differences were observed in the growth rates in vitro, but when grown in vivo as xenografts HIF-2 significantly increased, and HIF-1 significantly decreased growth rates, compared to EV tumors. Factors associated with proliferation were increased and factors associated with cell death were decreased in HIF-2+ tumors. Metabolite profiles showed higher glucose and lower lactate and alanine levels in the HIF-2+ tumors whilst immunostaining demonstrated higher pyruvate dehydrogenase and lower pyruvate dehydrogenase kinase 1, compared to control tumors. Taken together, these results suggest that overexpression of HIF-2 in CCRCC 786-0 tumors regulated growth both by maintaining a low level of glycolysis and by allowing more mitochondrial metabolism and tolerance to ROS induced DNA damage. The growth profiles observed may be mediated by adaptive changes to a more oxidative phenotype.

  8. Assessment of occult cervical lymph node metastasis in primary squamous cell carcinoma of the head and neck by computed tomography

    International Nuclear Information System (INIS)

    Shakil, U.

    2015-01-01

    To determine the frequency of occult (node negative) cervical lymph node metastasis in primary head and neck squamous cell carcinoma, using contrast enhanced computed tomography (CT). Study Design: Cross sectional descriptive study. Place and Duration of Study: Study was conducted in Department of Radiology, Combined Military Hospital Rawalpindi. Duration of the study was 06 months i.e. from 19th February 2011 to 19th August 2011. Patients and Methods: A total of 141 cases, fulfilling the inclusion criteria, reporting to the radiology department, were included in the study after seeking written informed consent. All patients underwent contrast enhanced CT scan of the neck from base of skull to root of neck using Asteion Whole Body X-ray CT Scanner (Model TSX-021A). Images were evaluated for the presence or absence of cervical lymph node metastasis according to the cervical lymph node metastatic criteria at each level of the neck. Results: Of the 141 patients with clinically no head and neck squamous cell carcinoma, 45.4% were found to have lymph node metastases. Frequency of occult metastases in squamous cell carcinoma of oral cavity was 47.6%, oropharynx 23.5%, larynx 33.3% and hypopharynx 78.6%. Conclusion: In clinically node negative neck, the risk of lymph node metastases is significantly high in patients of head and neck squamous cell carcinoma in our population. All patients presenting with node negative neck should undergo CT scans for early detection of occult metastasis. (author)

  9. Efficacy of transvaginal contrast-enhanced MRI in the early staging of cervical carcinoma

    International Nuclear Information System (INIS)

    Akata, Deniz; Kerimoglu, Ulku; Hazirolan, Tuncay; Karcaaltincaba, Musturay; Oezmen, Mustafa N.; Akhan, Okan; Koese, Faruk

    2005-01-01

    The objective of this study was to evaluate the efficacy of transvaginal contrast for local staging of cervical carcinoma. Fifty patients diagnosed with cervical carcinoma prospectively underwent magnetic resonance (MR) imaging before and after vaginal opacification (VO) with a mixture of 25 ml saline and 25 ml barium. T2-weighted (T2W) TSE images in axial and sagittal planes were compared before and after vaginal opacification. Dynamic T1W images in sagittal and fat-suppressed T1W images in transverse planes were also evaluated after intravenous contrast administration. Involvement of vaginal wall, lumen, and fornices; parametrium; rectum; and bladder were noted. Changes in local tumor staging and in treatment planning were also assessed after vaginal opacification. MR results were later compared with surgical pathological findings. Twenty-eight patients who went through surgical staging were included in the study. VO did not change any of the MR interpretations in 14 patients (50%). Correct staging was achieved with T2W TSE images with and without VO (in sagittal and transverse planes) in 78.5% and 50% of the patients, respectively. VO correctly lowered staging in seven and increased it in three patients compared with sagittal standard T2W images. Treatment planning was also changed in four (14%) of these patients. When overall accuracy of MR staging to indicate the appropriate treatment was evaluated, patients would have received the proper treatment in 90% and 79% of the cases when only T2W sagittal images with and without VO were evaluated, respectively. Dynamic gradient-echo images in sagittal planes and postcontrast T1W images in transverse planes evaluated with T2W series after VO, accomplished correct staging in 23 (82%) of the patients. MRI staging in early cervical cancer may be difficult and overestimated, especially if the tumor is slightly extended into the proximal vagina. Use of vaginal contrast medium is an easy, well-tolerated, and effective

  10. Type III radical hysterectomy after induction chemotherapy for patients with locally advanced cervical carcinoma.

    Science.gov (United States)

    Lopez-Graniel, C; Reyes, M; Chanona, G; Gonzalez, A; Robles, E; Mohar, A; Lopez-Basave, H; De La Garza, J G; Dueñas-Gonzalez, A

    2001-01-01

    Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical carcinoma. The aim of this study was to evaluate the feasibility, technical aspects, and clinical results of surgery after induction chemotherapy in this patient population. Forty-one untreated cervical carcinoma patients staged as IB2 to IIIB received three 21-day courses of cisplatin 100mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 followed by surgery or concomitant chemoradiation. The response to chemotherapy, operability, surgical/pathological findings, disease-free period, and survival of the surgically treated patients were evaluated. All 41 patients were evaluated for toxicity and 40 were evaluated for response. The overall objective response rate was 95% (95% confidence interval 88%-100%), and was complete in three patients (7.5%) and partial in 35 (87.5%). Granulocytopenia grades 3/4 occurred in 13.8% and 3.4% of the courses, respectively, whereas nonhematological toxicity was mild. Twenty-three patients underwent type III radical hysterectomy. Mean duration of surgery was 3.8 h (range 2:30-5:20), median estimated blood loss was 670 ml and median hospital stay was 5.2 days. Intraoperative complications occurred in one case (venous injury). In all but one case the resection margins were negative. Four patients (17%) had positive nodes (one node each); six (26%) had complete pathologic response, three (13%) had microscopic; and 14 (60%) macroscopic residual disease. At 24 months of maximum follow-up (median 20), the disease-free and overall survival rates were 59% and 91%, respectively. Induction chemotherapy with cisplatin/gemcitabine produced a high response rate and did not increase the difficulty of surgery. Operating time, blood loss, intraoperative complications, and hospital stay were all within the range observed for type III hysterectomy in early stage patients. We therefore conclude that type III radical hysterectomy is feasible in locally

  11. Cervicitis

    Science.gov (United States)

    ... of a woman getting HIV from an infected sexual partner. Prevention To reduce your risk of cervicitis from sexually transmitted infections, use condoms consistently and correctly each time you have sex. ...

  12. The late occurrence of urinary tract damage in patients successfully treated by radiotherapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Zoubek, J.; McGuire, E.J.; Noll, F.; DeLancey, J.O.

    1989-01-01

    Urinary tract complications apparently resulting from radiation therapy for carcinoma of the cervix can occur as long as 30 years after cessation of such treatment. Patients generally present with urinary incontinence and often are treated by standard operative methods that usually are unsuccessful. Incontinence is related to bladder fibrosis, urethral nonfunction and vesicovaginal fistuLa formation, and may be accompanied by bilateral ureteral obstruction. Of 11 patients with late complications of radiotherapy 4 had upper tract deterioration, 4 had vesicovaginal fistulas, 5 had an incompetent urethra aNd 9 had a fibrotic, noncompliant areflexive bladder. Treatment was aimed at providing adequate low pressure storage capacity and consisted of augmentation cystoplasty in 5 patients, repair of the fistula in 4 and correction of urethral dysfunction in 5. Women who complain of incontinence and/or irritable bladder symptoms with a history of radiotherapy for cervical carcinoma should be evaluated for fistuLa formation, urethral incompetence, and detrusor areflexia and fibrosis before treatment is done

  13. Radiotherapy for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site

    International Nuclear Information System (INIS)

    Colletier, Philip J.; Garden, Adam S.; Morrison, William H.; Geara, Fady B.; Kian Ang, K.

    1996-01-01

    PURPOSE/OBJECTIVE: To evaluate the outcome of patients treated with radiotherapy for carcinoma metastatic to cervical lymph nodes from an unknown primary site. This large retrospective series updates the results of our treatment policy in which patients receive radiation both to the involved neck(s) at risk as well as putative mucosal primary sites along the pharyngeal axis. MATERIALS/METHODS: Between July 1968 and December 1992, 196 patients with carcinoma metastatic to cervical lymph nodes from an unknown primary site were treated with curative intent using megavoltage external beam radiotherapy. One hundred thirty-nine patients received adjuvant radiation following either an excisional biopsy or neck dissection (S+XRT), and 57 received radiation to gross disease following either a diagnostic biopsy or incomplete resection (XRT). A neck dissection was performed following radiation in patients in the XRT group who were medically and technically operable if there were residual masses following radiation. Nodal stage distribution was as follows: N1 - 32 patients, N2a - 65, N2b - 35, N2c - 15, N3 - 36, and NX - 13. Thirty percent of patients in the XRT group had N3 disease vs. 14% in the S+XRT group (p = .008). Similarly, 33% of patients in the XRT group presented with low jugular or supraclavicular adenopathy compared with 16% in the S+XRT group (p = .006). Radiation was delivered to putative mucosal sites in 173 patients. Of these, 172 were treated to the oropharynx, 167 to the nasopharynx, 124 to the larynx and hypopharynx, and 5 to the oral cavity. All but one patient received bilateral treatment when covering putative mucosal primary sites. Treatment was limited to the ipsilateral neck only in 23 patients. Doses ranged from 24 to 90 Gy. The median doses to the sites of nodal involvement were 63 Gy and 68.1 Gy for the S+XRT and XRT groups, respectively. RESULTS: The range of follow-up was 1-267 months with a median follow-up in surviving patients of 87 months

  14. Clinical-pathologic correlation in early cervical carcinoma: CT-MR imaging comparison for effect on staging and treatment choices

    International Nuclear Information System (INIS)

    Rubens, D.; Thornbury, J.R.; Weiss, S.L.; Lerner, R.M.; Angel, C.; Beecham, J.; Stoler, M.H.

    1986-01-01

    A group of patients with clinical stage I or II squamous cell cervical carcinoma have been examined using a 1.5-T magnet. Of these, six have had radical hysterectomy (by April 1986), providing specimens for pathologic correlation. In this preliminary group of patients, MR imaging gave a more accurate assessment of primary tumor extent than did clinical staging. In three of six patients, the disease was underestimated clinically at examination under anesthesia. These patients would have been managed with preoperative radiation rather than surgery alone if the investigative MR imaging information had been used in treatment planning. CT examinations of these patients did not contribute useful information for patient management. Preoperative MR imaging has the potential to alter patient treatment in early cervical carcinoma

  15. Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

    Science.gov (United States)

    Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

    2014-02-01

    Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

  16. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  17. Laparoscopic sentinel lymph node procedure using a combination of patent blue and radioisotope in women with cervical carcinoma.

    Science.gov (United States)

    Barranger, Emmanuel; Grahek, Dany; Cortez, Annie; Talbot, Jean Noel; Uzan, Serge; Darai, Emile

    2003-06-15

    The authors evaluated the feasibility of a laparoscopic sentinel lymph node (SN) procedure with combined radioisotopic and patent blue labeling in patients with cervical carcinoma. Thirteen women (median age, 52.5 years) with cervical carcinoma (Stage Ia2 in 1 patient, Stage Ib1 in 10 patients, Stage Ib2 in 1 patient, and Stage IIa in 1 patient) underwent a laparoscopic SN procedure using an endoscopic gamma probe after both radioactive isotope and patent blue injections. After the procedure, all patients underwent complete laparoscopic pelvic lymphadenectomy and either laparoscopic radical hysterectomy (eight patients) or the Schauta-Amreich operation (five patients). SNs (mean, 1.7 SNs per patient; range, 1-3 SNs per patient) were identified in 12 of 13 patients. A median of 10.5 pelvic lymph nodes per patient (range, 4-17 pelvic lymph nodes per patient) were removed. No lymph node involvement was detected in SNs with hematoxylin and eosin staining. Immunohistochemical studies identified four metastatic SNs in two patients, with micrometastases in two SNs from the first patient and isolated tumor cells in two SNs from the second patient. No false-negative SN results were obtained. The results of this study suggest that SN detection with a combination of radiocolloid and patent blue is feasible in patients with cervical carcinoma. The combination of laparoscopy and the SN procedure permitted minimally invasive management of early-stage disease. Copyright 2003 American Cancer Society.

  18. Efficacy and prognostic analysis of chemoradiotherapy in patients with thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis alone

    International Nuclear Information System (INIS)

    Zhang, Peng; Xi, Mian; Zhao, Lei; Li, Qiao-Qiao; He, Li-Ru; Liu, Shi-Liang; Shen, Jing-Xian; Liu, Meng-Zhong

    2014-01-01

    The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50–68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival

  19. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Calmon, Marilia Freitas [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil); Sichero, Laura [Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo (Brazil); Boccardo, Enrique [Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo (Brazil); Villa, Luisa Lina [Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo (Brazil); Rahal, Paula, E-mail: rahalp@yahoo.com.br [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil)

    2016-09-15

    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

  20. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique; Villa, Luisa Lina; Rahal, Paula

    2016-01-01

    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

  1. Possible association between stem-like hallmark and radioresistance in human cervical carcinoma cells.

    Science.gov (United States)

    Kumazawa, Shoko; Kajiyama, Hiroaki; Umezu, Tomokazu; Mizuno, Mika; Suzuki, Shiro; Yamamoto, Eiko; Mitsui, Hiroko; Sekiya, Ryuichiro; Shibata, Kiyosumi; Kikkawa, Fumitaka

    2014-05-01

    We aimed to investigate the possibility of an association between a stem-like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells. Side-population (SP) cells and non-SP (NSP) cells in HeLa cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed Western blot analysis to evaluate the expression of stem cell markers (CXCR4, Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP and NSP cells were injected into nude mice and we assessed subcutaneous tumor formation. To examine tolerance of irradiation, colony formation and apoptosis change were confirmed in the SP and NSP cells. SP cells showed a higher expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP cells were easily induced to undergo apoptosis. SP cells tended to form spheroids and showed a higher level of tumorigenicity compared with NSP cells. In addition, nude mice inoculated with SP cells showed greater tumor growth compared with NSP cells. SP cells showed a higher tumorigenicity and lower apoptotic potential, leading to enhanced radiotolerance. Tumor SP cells showed higher-level stem-cell-like characters and radioresistance than NSP cells. SP cells may be useful for new therapeutic approaches for radiation-resistant cervical cancer. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  2. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy.

    Science.gov (United States)

    Seki, Masafumi; Iwakawa, Jun; Cheng, Helen; Cheng, Pi-Wan

    2002-04-10

    We previously reported that supplementation of a cationic liposome with transferrin (Tf) greatly enhanced lipofection efficiency (P.-W. Cheng, Hum. Gene Ther. 1996;7:275-282). In this study, we examined the efficacy of p53 and PTEN tumor suppressor gene therapy in a mouse xenograft model of human prostate PC-3 carcinoma cells, using a vector consisting of dimyristoyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE)-cholesterol (DC) and Tf. When the volume of the tumors grown subcutaneously in athymic nude mice reached 50-60 mm(3), three intratumoral injections of the following four formulations were performed during week 1 and then during week 3: (1) saline, (2) DC + Tf + pCMVlacZ, (3) DC + Tf + pCMVPTEN, and (4) DC + Tf + pCMVp53 (standard formulation). There was no significant difference in tumor volume and survival between group 1 and group 2 animals. As compared with group 1 controls, group 3 animals had slower tumor growth during the first 3 weeks but thereafter their tumor growth rate was similar to that of the controls. By day 2 posttreatment, group 4 animals had significantly lower tumor volume relative to initial tumor volume as well as controls at the comparable time point. Also, animals treated with p53 survived longer. Treatment with DC, Tf, pCMVp53, DC + pCMVp53, or Tf + pCMVp53 had no effect on tumor volume or survival. Expression of p53 protein and apoptosis were detected in tumors treated with the standard formulation, thus associating p53 protein expression and apoptosis with efficacy. However, p53 protein was expressed in only a fraction of the tumor cells, suggesting a role for bystander effects in the efficacy of p53 gene therapy. We conclude that intratumoral gene delivery by a nonviral vector consisting of a cationic liposome and Tf can achieve efficacious p53 gene therapy of prostate cancer.

  3. Magnetic Resonance Tracking of Endothelial Progenitor Cells Labeled with Alkyl-Polyethylenimine 2 kDa/Superparamagnetic Iron Oxide in a Mouse Lung Carcinoma Xenograft Model

    Directory of Open Access Journals (Sweden)

    Cong Chen

    2014-11-01

    Full Text Available The potential of using endothelial progenitor cells (EPCs in novel anticancer therapy and the repair of vascular injury has been increasingly recognized. In the present study, EPCs were labeled with N-alkyl-polyethylenimine 2 kDa (PEI2k-stabilized superparamagnetic iron oxide (SPIO to facilitate magnetic resonance imaging (MRI of EPCs in a mouse lung carcinoma xenograft model. EPCs derived from human peripheral blood were labeled with alkyl-PEI2k/SPIO. The viability and activity of labeled cells were evaluated using proliferation, migration, and tubulogenesis assays. Alkyl-PEI2k/SPIO-labeled EPCs were injected intravenously (group 1 or mixed and injected together with A549 cells subcutaneously (group 2 into groups of six mice with severe combined immunodeficiency. The labeling efficiency with alkyl-PEI2k/SPIO at 7 mg Fe/mL concentration was approximately 100%. Quantitative analysis of cellular iron was 6.062 ± 0.050 pg/cell. No significant effects on EPC proliferation, migration, or tubulogenesis were seen after labeling. Seventesla micro-MRI showed the presence of schistic or linear hypointense regions at the tumor margins starting from days 7 to 8 after EPC administration. This gradually extended into the inner tumor layers in group 1. In group 2, tumor growth was accompanied by dispersion of low-signal intensity regions inside the tumor. Iron-positive cells identified by Prussian blue dye were seen at the sites identified using MRI. Human CD31-positive cells and mouse CD31-positive cells were present in both groups. Labeling EPCs with alkyl-PEI2k/SPIO allows noninvasive magnetic resonance investigation of EPC involvement in tumor neovasculature and is associated with excellent biocompatibility and MRI sensitivity.

  4. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

    1998-02-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

  5. Cytotoxic effects of alkaloids on cervical carcinoma cell lines: a review

    Directory of Open Access Journals (Sweden)

    Priscilla Alencar Fernandes

    2016-07-01

    Full Text Available Cervical cancer is the fourth type of women neoplasia, with thousands of new cases annually. It is closely related to human papillomavirus (HPV infection, which has more than 13 oncogenic types, among them HPV 16 and 18 are implicated in 70% of cervical carcinoma cases. Alkaloids are nitrogenated and naturally occurring compounds, showing several uses in medical treatment, including cytotoxic and antineoplastic activities. In this work we aim to evaluate the cytotoxic and chemotherapeutic potential of alkaloids against cervical cancer. In order to accomplish this purpose, we have made a survey of potentially effective alkaloids with cytotoxic activities over HPV-16+ and HPV-18 + cells (HeLa cells. Through a literature review between the years of 1980 and 2015, we described the major alkaloid sources, distribution in nature and also discussed the mechanisms of action for their cytotoxicity. We found that alkaloids showed efficacy as cytotoxic agents, inhibiting cell growth of the HPV-transformed cells in vitro and in vivo by means of activation of intrinsic and extrinsic pathways of apoptosis, which included the clivage of caspases and PARP-1 (Poli-Adenosyl- Ribose Protease 1, increase in p53 expression, release of cytochrome C and increase of cell death receptors expression like Fas, mainly observed in HeLa (HPV- 18 + cell lines. Moreover, these secondary metabolites helped in modulating the MDR (Multi-Drug Resistance against the cell lines studied, which lead us to suggest their possible use as chemotherapeutic agents on the lesions caused by these virusesKeywords: Cervical cancer. Alkaloids. HPV. Chemotherapy. RESUMOEfeitos citotóxicos de alcaloides sobre linhagens de células do câncer cervical: uma revisãoO câncer cervical é a quarta neoplasia incidente em mulheres, com o surgimento de milhares de novos casos anualmente. Está altamente relacionado à infecção pelo papilomavírus humano (HPV, que apresenta mais de 13 tipos oncog

  6. Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.

    Science.gov (United States)

    Holdenrieder, Stefan; Molina, Rafael; Qiu, Ling; Zhi, Xiuyi; Rutz, Sandra; Engel, Christine; Kasper-Sauer, Pia; Dayyani, Farshid; Korse, Catharina M

    2018-04-01

    In squamous cell carcinoma, squamous cell carcinoma antigen levels are often elevated. This multi-center study evaluated the technical performance of a new Elecsys ® squamous cell carcinoma assay, which measures serum squamous cell carcinoma antigen 1 and 2 levels in an equimolar manner, and investigated the potential of squamous cell carcinoma antigen for differential diagnosis of cervical, lung, and head and neck squamous cell carcinoma.Assay precision and method comparison experiments were performed across three European sites. Reference ranges for reportedly healthy individuals were determined using samples from banked European and Chinese populations. Differential diagnosis experiments determined whether cervical, lung, or head and neck cancer could be differentiated from apparently healthy, benign, or other malignant cohorts using squamous cell carcinoma antigen levels alone. Squamous cell carcinoma antigen cut-off levels were calculated based on squamous cell carcinoma antigen levels at 95% specificity. Repeatability coefficients of variation across nine analyte concentrations were ≤5.3%, and intermediate precision coefficients of variation were ≤10.3%. Method comparisons showed good correlations with Architect and Kryptor systems (slopes of 1.1 and 1.5, respectively). Reference ranges for 95th percentiles for apparently healthy individuals were 2.3 ng/mL (95% confidence interval: 1.9-3.8; European cohort, n = 153) and 2.7 ng/mL (95% confidence interval: 2.2-3.3; Chinese cohort, n = 146). Strongest differential diagnosis results were observed for cervical squamous cell carcinoma: receiver operating characteristic analysis showed that squamous cell carcinoma antigen levels (2.9 ng/mL cut-off) differentiate cervical squamous cell carcinoma (n = 127) from apparently healthy females (n = 286; area under the curve: 86.2%; 95% confidence interval: 81.8-90.6; sensitivity: 61.4%; specificity: 95.6%), benign diseases (n = 187; area

  7. Blocking Modification of Eukaryotic Initiation 5A2 Antagonizes Cervical Carcinoma via Inhibition of RhoA/ROCK Signal Transduction Pathway.

    Science.gov (United States)

    Liu, Xiaojun; Chen, Dong; Liu, Jiamei; Chu, Zhangtao; Liu, Dongli

    2017-10-01

    Cervical carcinoma is one of the leading causes of cancer-related death for female worldwide. Eukaryotic initiation factor 5A2 belongs to the eukaryotic initiation factor 5A family and is proposed to be a key factor involved in the development of diverse cancers. In the current study, a series of in vivo and in vitro investigations were performed to characterize the role of eukaryotic initiation factor 5A2 in oncogenesis and metastasis of cervical carcinoma. The expression status of eukaryotic initiation factor 5A2 in 15 cervical carcinoma patients was quantified. Then, the effect of eukaryotic initiation factor 5A2 knockdown on in vivo tumorigenicity ability, cell proliferation, cell cycle distribution, and cell mobility of HeLa cells was measured. To uncover the mechanism driving the function of eukaryotic initiation factor 5A2 in cervical carcinoma, expression of members within RhoA/ROCK pathway was detected, and the results were further verified with an RhoA overexpression modification. The level of eukaryotic initiation factor 5A2 in cervical carcinoma samples was significantly higher than that in paired paratumor tissues ( P cycle arrest ( P ROCK I, and ROCK II were downregulated. The above-mentioned changes in eukaryotic initiation factor 5A2 knockdown cells were alleviated by the overexpression of RhoA. The major findings outlined in the current study confirmed the potential of eukaryotic initiation factor 5A2 as a promising prognosis predictor and therapeutic target for cervical carcinoma treatment. Also, our data inferred that eukaryotic initiation factor 5A2 might function in carcinogenesis of cervical carcinoma through an RhoA/ROCK-dependent manner.

  8. MVP expression is related to IGF1-R in cervical carcinoma patients treated by radiochemotherapy.

    Science.gov (United States)

    Lloret, Marta; Lara, Pedro Carlos; Bordón, Elisa; Rey, Agustin; Falcón, Orlando; Apolinario, Rosa Maria; Clavo, Bernardino; Ruiz, Ana

    2008-09-01

    To assess the expression of MVP in cervix carcinoma patients treated by radiochemotherapy, its relation to clinical and pathologic prognostic factors and its role in predicting clinical outcome. In addition the relation to IGF-1R expression in this cohort of patients will be explored. Sixty consecutive patients suffering from localized cervix carcinoma were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in November 2007. Patients were staged following the TNM classification. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) followed brachytherapy and concomitant cisplatin at 40 mg/m(2)/week doses. MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. MVP was expressed in 58 patients (96.7%) and no relation was found with clinicopathological variables. High MVP expression was related to high IGF1-R expression (p=0.023). Complete response after treatment was observed in 50 patients (83.3%). Clinical stage of the disease and clinical response to radiochemotherapy were the most important prognostic factors related to survival. High MVP and IGF-1R tumour expression was strongly related to poor local and regional disease-free survival (p=0.006), distant disease-free survival (p=0.050), disease-free survival (p=0.006), and cause-specific survival (p=0.007) in patients achieving a complete response. MVP and IGF-1R expression were related in clinical cervical tumours and confer reduced long-term local control in patients who achieved clinical complete response to radiochemotherapy.

  9. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-07-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

  10. Outcome of treatment of upper third vaginal recurrences of cervical and endometrial carcinomas with interstitial brachytherapy

    International Nuclear Information System (INIS)

    Charra, C.; Roy, P.; Coquard, R.; Romestaing, P.; Ardiet, J.M.; Gerard, J.P.

    1998-01-01

    Purpose: To describe an original brachytherapy technique using a dedicated intravaginal template for the treatment of vaginal vault recurrences and to evaluate the results of such a treatment. Methods and Materials: Between 1978 and 1993, 78 patients with isolated recurrence of cervical or endometrial carcinoma located in the vaginal vault have been treated in Lyon. Initial treatment was surgery alone in 49 cases and irradiation with surgery in 37 cases. Treatment of the vaginal recurrence was performed with interstitial Iridium 192 brachytherapy combined with pelvic external beam radiation therapy in 34 patients. The tumor was implanted with a dedicated intravaginal plastic template. Six parallel metallic needles were implanted in the vaginal vault and afterloaded with Iridium 192 wires of 4 to 6 cm long. The mucosa of the upper half of the vagina received the same dose as the one encompassing the tumor on the 85% isodose of the Paris system. Results: At 5 years the local control rate was 70% and the overall survival rate 56%. Grade 3 complications occurred in 10% of the cases and only in patients who had received irradiation during the initial treatment of the primary tumor. Conclusions: This brachytherapy technique makes it possible to perform Iridium 192 implants in a difficult situation with a favorable long-term control rate and an acceptable rate of complications

  11. Carcinoma of the cervical esophagus treated with radiation therapy using a four-field box technique

    International Nuclear Information System (INIS)

    Mendenhall, W.M.; Million, R.R.; Bova, F.J.

    1982-01-01

    This is a retrospective analysis of 16 patients with carcinoma of the cervical esophagus treated with radiation therapy at the University of Florida between September 1966 and March 1979. There is a minimum 2-year followup. Analysis of local control revealed 1/1 T1, 0/3 T2, 2/8 T3, and 1/2 TX lesions that were controlled by radiation therapy for 33, 47, 55, and 80 months. Two patients died less than 2 years after treatment without evidence of cancer. Excluding the sole T1 lesion, there were no local controls below 6700 rad; 3 of 5 lesions were controlled at doses in excess of 6700 rad. Late complications were stenosis (2 patients) and Lhermitte's syndrome (1 patient). An external beam technique consisting of an isocentric four-field box with a beeswax compensator has been devised in an effort to solve the technical problems in delivering high-dose radiation to the primary and regional nodes without producing myelitis

  12. Two cases of pyogenic osteomyelitis of pubic bone after irradiation for cervical carcinoma of the uterine

    International Nuclear Information System (INIS)

    Moriyama, Ichiro; Matsumoto, Morio; Yamauchi, Kenji; Horiuchi, Kiwamu; Morisue, Hikaru; Yamagishi, Masaaki; Tanaka, Mamoru

    1999-01-01

    Two cases of pyogenic osteomyelitis of pubic bone occurred after irradiation of cervical carcinoma were reported. Case 1: A 69-year-old female received external irradiation of 50 Gy from November 1993 to April 1994 after supravaginal uterine amputation. The left melosalgia and pain at left pubic region appeared from July 1994. On the MRI, bone marrow of the left pubic region showed low brightness by T1 weighted image and equal brightness by T2 weighted image, and the image was enhanced by gadolinium. An abscess in external obturator muscle was suspected. High accumulation was recognized by bone scintigram at the left pubic region. No bacterial infection was recognized. Focus was removed in May 1995. Case 2: A 80-year-old female received external irradiation of 50 Gy and intracavitary irradiation of 30 Gy in May 1992. Pain at left pubic region appeared from June 1993. Dilation of pubic symphysis and osteoclasia of the left pubic bone were detected on the plain radiograph in March 1995. On the MRI, the left pubic bone marrow showed low brightness by T1 weighted image and equal brightness by T2 weighted image, and image was enhanced by gadolinium. An abscess in small pelvic cavity was suspected. Streptococcus agalactae was detected in abscess, and PIPC was administered by drip infusion for five weeks. They are currently alive and doing well about three years later. (K.H.)

  13. The Role of Cyclins and Cyclins Inhibitors in the Multistep Process of HPV-Associated Cervical Carcinoma

    International Nuclear Information System (INIS)

    Bahnassy, A.A.; Mokhtar, N.M.; Zekri, A.; Alam El-Din, H.M.; Aboubaker, A.A.; Kamel, K.; El-Sabah, M.T.

    2006-01-01

    Background: Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. Methods: We investigated 110 subjects (43 invasive squamous cell carcinoma [ISCC], 38 CIN Ill, II CIN II, 18 CIN I) confirmed to be positive for HPV 16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin DJ, cyclin E, CDK4, cyclin inhibitors (p2Jwa/; p27, pI6/NK4A) and Ki-67 using immunohistochemistry and differential PCR techniques. Results: There was a significant increase in the expression of Ki-67, cyclin E, CDK4, pJ6/NK4A (p=0003, 0.001,0.001) and a significant decrease in p27K1P/ from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27K1P I and p 161NK4A (p KIpl (ρ=0.011) in all studied groups In ISCC, there was significant relationship between standard clinico-pathological prognostic factors and high Ki-67 index, increased cyclin D J and cyclin E, reduced p2 7Kip / and p21 waf Conclusion: I) Aberrations involving p27K/P 1, cyclin E, CDK4 and pJ6/NK4A are considered early events in HPV 16 and IS-associated cervical carcinogenesis (CINI and lI), whereas cyclin DI aberrations are late events (CINIII and ISCC). 2) immunohistochemical tests for pJ61NK4A and cyclin E could help in early diagnosis of cervical carcinoma. 3) Only FIGO stage, cyclin DI, p27K1P1 and Ki-67 are independent prognostic factors that might help in predicting outcome of cervical cancer palients

  14. Oral Rigosertib for Squamous Cell Carcinoma

    Science.gov (United States)

    2017-06-22

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  15. Human papillomavirus genotypes in invasive cervical squamous cell carcinoma in Trinidad Genotipos de virus de los papilomas humanos en carcinoma cervicouterino escamocelular invasor en Trinidad

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    Felicia Hosein

    2013-04-01

    Full Text Available OBJECTIVE: To determine the relative contribution of known high-risk human papillomavirus (HPV genotypes to the occurrence of cervical cancers in Trinidad. METHODS: The distribution of HPV genotypes in cases of invasive cervical squamous cell carcinoma in Trinidad was investigated. This study was a follow-up to an investigation of HPV genotypes in 310 nonsymptomatic women in Trinidad. The latter study showed that cervical HPV prevalence and heterogeneity of genotypes were high in the study population; notably, the genotypes targeted by the available HPV prophylactic vaccines were not the most common types. RESULTS: The current study of 85 cases of invasive cervical squamous cell carcinomas demonstrated that the previously observed heterogeneity in HPV genotype distribution is lost in cases of invasive cervical cancer, with the vaccine-targeted HPV types HPV 16 and HPV 18 becoming the most prevalent. CONCLUSIONS: HPV 16 and HPV 18 were the primary HPV genotypes associated with cases of invasive squamous cell carcinoma in the current Trinidad study. This strong association leads us to conclude that the HPV vaccines targeting HPV 16 and HPV 18 may contribute to reducing the cervical cancer burden in Trinidad.OBJETIVO: Determinar la contribución relativa de los diferentes genotipos de virus de los papilomas humanos (VPH conocidos como de alto riesgo para la aparición de cáncer cervicouterino en Trinidad. MÉTODOS: Se investigó la distribución de los genotipos de VPH en casos de carcinoma cervicouterino escamocelular invasor en Trinidad. Este estudio fue la continuación de una investigación de los genotipos de VPH presentes en 310 mujeres asintomáticas en Trinidad. Este último estudio reveló altas prevalencia de VPH en el cuello uterino y heterogeneidad de los genotipos en la población del estudio; cabe destacar que los genotipos a los que se dirigen las vacunas preventivas de la infección por VPH disponibles no fueron los tipos m

  16. Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

    Science.gov (United States)

    2018-05-23

    Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

  17. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3beta is implicated in the treatment of cervical carcinoma.

    Science.gov (United States)

    Zhang, Yuan; Shu, Yi Min; Wang, Shu Fang; Da, Bang Hong; Wang, Ze Hua; Li, Hua Bin

    2010-02-23

    PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3beta (GSK-3beta) in chemosensitivity. We examined PMS2 and phosphorylated GSK-3beta(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3beta after transfection with GSK-3beta by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3beta (s9). Furthermore, we demonstrated GSK-3beta transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Our results provide the evidence that stabilization of PMS2 production by GSK-3beta was important to improve chemosensitization, indicating the significance of GSK-3beta-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.

  18. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma

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    Wang Ze

    2010-02-01

    Full Text Available Abstract Background PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3β (GSK-3β in chemosensitivity. Methods We examined PMS2 and phosphorylated GSK-3β(s9 expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3β after transfection with GSK-3β by small interference RNA (siRNA, co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. Results We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3β (s9. Furthermore, we demonstrated GSK-3β transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Conclusions Our results provide the evidence that stabilization of PMS2 production by GSK-3β was important to improve chemosensitization, indicating the significance of GSK-3β-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.

  19. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuan [Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Shu, Yi Min [Allergy and Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China); Wang, Shu Fang [Department of Pathology, Baylor College of Medicine, Houston, TX 77030 (United States); Da, Bang Hong; Wang, Ze Hua [Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Li, Hua Bin [Allergy and Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China); Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611 (United States)

    2010-02-23

    PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3β (GSK-3β) in chemosensitivity. We examined PMS2 and phosphorylated GSK-3β(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3β after transfection with GSK-3β by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3β (s9). Furthermore, we demonstrated GSK-3β transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Our results provide the evidence that stabilization of PMS2 production by GSK-3β was important to improve chemosensitization, indicating the significance of GSK-3β-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.

  20. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma

    Science.gov (United States)

    2010-01-01

    Background PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3β (GSK-3β) in chemosensitivity. Methods We examined PMS2 and phosphorylated GSK-3β(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3β after transfection with GSK-3β by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. Results We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3β (s9). Furthermore, we demonstrated GSK-3β transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Conclusions Our results provide the evidence that stabilization of PMS2 production by GSK-3β was important to improve chemosensitization, indicating the significance of GSK-3β-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy. PMID:20178594

  1. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma

    International Nuclear Information System (INIS)

    Zhang, Yuan; Shu, Yi Min; Wang, Shu Fang; Da, Bang Hong; Wang, Ze Hua; Li, Hua Bin

    2010-01-01

    PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3β (GSK-3β) in chemosensitivity. We examined PMS2 and phosphorylated GSK-3β(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3β after transfection with GSK-3β by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3β (s9). Furthermore, we demonstrated GSK-3β transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Our results provide the evidence that stabilization of PMS2 production by GSK-3β was important to improve chemosensitization, indicating the significance of GSK-3β-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy

  2. Contribution of mono-exponential, bi-exponential and stretched exponential model-based diffusion-weighted MR imaging in the diagnosis and differentiation of uterine cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Meng; Yu, Xiaoduo; Chen, Yan; Ouyang, Han; Zhou, Chunwu [Chinese Academy of Medical Sciences, Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Beijing (China); Wu, Bing; Zheng, Dandan [GE MR Research China, Beijing (China)

    2017-06-15

    To investigate the potential of various metrics derived from mono-exponential model (MEM), bi-exponential model (BEM) and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in diagnosing and differentiating the pathological subtypes and grades of uterine cervical carcinoma. 71 newly diagnosed patients with cervical carcinoma (50 cases of squamous cell carcinoma [SCC] and 21 cases of adenocarcinoma [AC]) and 32 healthy volunteers received DWI with multiple b values. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (alpha), and distributed diffusion coefficient (DDC) were calculated and compared between tumour and normal cervix, among different pathological subtypes and grades. All of the parameters were significantly lower in cervical carcinoma than normal cervical stroma except alpha. SCC showed lower ADC, D, f and DDC values and higher D* value than AC; D and DDC values of SCC and ADC and D values of AC were lower in the poorly differentiated group than those in the well-moderately differentiated group. Compared with MEM, diffusion parameters from BEM and SEM may offer additional information in cervical carcinoma diagnosis, predicting pathological tumour subtypes and grades, while f and D showed promising significance. (orig.)

  3. Expression of Bmi-1, P16, and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance

    International Nuclear Information System (INIS)

    Weng, Mei-ying; Li, Lin; Feng, Shu-ying; Hong, Shun-jia

    2012-01-01

    Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. The present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma (UCC). A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used in the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed. The expression of Bmi-1, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa (P<0.05). The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis (P<0.01) and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization (P<0.05). Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features (P>0.05). The Kaplan–Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients (P<0.05). A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC (r=0.419, P=0.001). The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the

  4. Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Her-2 Protein in the Genesis of Cervical Carcinoma.

    Science.gov (United States)

    Rahmani, Arshad H; Babiker, Ali Yousif; Alsahli, Mohammed A; Almatroodi, Saleh A; Husain, Nazik Elmalaika O S

    2018-02-15

    Angiogenesis plays a pivotal role in the progression of tumours through the formation of new blood vessels. Vascular endothelial growth factor (VEGF) is a chief factor responsible for inducing and regulating angiogenesis. Additionally, the human epidermal growth factor receptor family of receptors also plays an important role in the pathogenesis of tumours. This study aimed to examine the association between VEGF and Her-2 protein expression and its correlation with clinic-pathological characteristics; in particular, prognosis. A total of 65 cases of cervical carcinoma and 10 samples of inflammatory lesions were evaluated for VEGF and Her-2 protein expression. Expression of VEGF and Her-2 was detected in 63.07% and 43.07% in cervical carcinoma cases respectively whereas control cases did not show any expression. The difference in the expression pattern of both markers comparing cancer and control cases was statistically significant (p 0.05). Comparing different grades of a tumour, expression of Her-2 was detected in 31.8% of well-differentiated tumours, 36.0 % in moderately differentiated tumours and 66.66 % in poorly differentiated cancers. The expression of Her-2 was increased in high-grade tumours, and the difference of expression level between tumour grades was statistically significant (p 0.05). The present study supports earlier findings that over-expression / up-regulation of VEGF and Her - 2 is linked with poor prognosis and may play a vital role in the development and progression of cervical cancer.

  5. Cervical lymph node metastases in salivary gland adenoid cystic carcinoma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ning C

    2018-06-01

    Full Text Available Chunliu Ning,1 Tengfei Zhao,1 Zechen Wang,1 Delong Li,1 Yurong Kou,2 Shaohui Huang1 1Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Oral Biology, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China Background: The purpose of this research was to determine whether neck dissection is necessary for the adenoid cystic carcinoma (ACC of head and neck. Materials and methods: This article screened the abstract and full-text papers that investigated salivary gland primary ACC of head and neck. Two independent reviewers searched for articles published before October 2017 in three databases (Web of Science, PubMed, and Ovid, having no limits in date and language. Statistical data were analyzed statistically by Review Manager 5.3. Results: In total, 18 studies involving 2993 patients were included in the analysis. Of the 2993 patients, 473 patients had cervical lymph node metastasis, with a merge frequency of 16% (95% CI: 13–19. Among included articles, only 4 involved cervical lymph node occult metastases, with a merge frequency of 14% (95% CI: 9–20. There were 5 articles containing minor salivary glands (MiSGs involving 370 patients of which 92 patients had cervical lymph node metastases and the merge frequency was 25% (95% CI: 11–38. Moreover, there were 4 studies on major salivary glands involving 904 patients of which 158 patients had cervical lymph node metastases and the merge frequency was 17% (95% CI: 15–20. Conclusion: Elective neck dissection is unnecessary for all patients with salivary gland ACC of head and neck. Moreover, compared with major salivary glands, MiSGs have a higher cervical lymph node metastases rate in ACC. The overall cervical lymph node metastases rate of MiSGs is 25%, which is enough to attract our attention. Therefore, we suggest that neck dissection might be

  6. Applicability of preoperative nuclear morphometry to evaluating risk for cervical lymph node metastasis in oral squamous cell carcinoma.

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    Masaaki Karino

    Full Text Available BACKGROUND: We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma. METHODS: A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio, and nuclear area coefficient of variation (NACV. Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis. RESULTS: Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in node-negative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site. CONCLUSION: Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma.

  7. A comparison of concurrent chemoradiotherapy and radiotherapy in Chinese patients with locally advanced cervical carcinoma: a multi-center study

    International Nuclear Information System (INIS)

    Li, Zhijie; Yang, Shuyan; Liu, Lei; Han, Shiyu

    2014-01-01

    We investigated the efficacy of concurrent chemoradiotherapy (CCRT) over radiotherapy (RT) in Chinese patients with locally advanced cervical carcinoma. Between January 2005 and January 2008, 192 patients with squamous cell carcinoma of the cervix were included in the study: 96 in arm A (CCRT with 20 mg/m 2 cisplatin for 5 days) and 96 in arm B (RT). The overall response rate was the primary endpoint. The secondary endpoints included overall survival, progression-free survival, and toxicity. The 5-year overall response rate was 67% and 53% for the CCRT and RT arms, respectively, and the difference was statistically significant, while the median overall survival was 68 months (range 3-85 months) and 61 months (range 4-83 months), respectively (P = 0.009). In addition, the median progression-free survival for CCRT was 62 months (range 3-83 months), whereas it was 51 months (range 4-81 months) for the RT arm (P = 0.025). The toxicity profile, both acute and late, was comparable in both arms. In summary, we demonstrate that CCRT was effective and better tolerated than RT alone in Chinese patients with locally advanced cervical carcinoma.

  8. Putative stem cell markers in cervical squamous cell carcinoma are correlated with poor clinical outcome

    International Nuclear Information System (INIS)

    Hou, Teng; Zhang, Weijing; Tong, Chongjie; Kazobinka, Gallina; Huang, Xin; Huang, Yongwen; Zhang, Yanna

    2015-01-01

    The aim of this study was to elucidate the value of putative cancer stem cell markers Musashi-1, ALDH1, Sox2, and CD49f in predicting the prognosis in cervical squamous cell carcinoma (CSCC). Real-time PCR and immunohistochemistry staining was performed to examine Musashi-1, ALDH1, Sox2, and CD49f expression in archived specimens of CSCC patients with postoperative chemotherapy. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of CSC markers for overall survival (OS) and recurrent-free survival (RFS). The Real-time PCR data showed that the expression of all markers were increased in CSCC tissues compared with in paired normal cervical tissues (P < 0.05). The IHC result showed that high expression of Msi1, ALDH1, Sox2, and CD49f was found in 25.7 %, 43.0 %, 62.0 % and 29.0 % CSCC samples, respectively. Moreover, high expression of Msi1 (P = 0.033 and P = 0.003, respectively), ALDH1 (P = 0.015 and P = 0.002, respectively), and Sox2 (P = 0.005 and P = 0.003, respectively), and low expression of CD49f (P = 0.027 and P = 0.025, respectively) were correlated with poor OS and PFS in CSCC patients. Interestingly, tumors with Msi1 high /CD49f low expression had the poorest prognosis according to Msi1/CD49f stratification. In multivariate Cox regression analysis, Sox2 expression (P = 0.047 and P = 0.018, respectively), ALDH1 expression (P = 0.013 and P = 0.003, respectively), and CD49f expression (P = 0.008 and P = 0.003, respectively) were independent prognostic markers for both OS and RFS. Our results suggest that cancer stem cell markers are linked with poor prognosis of CSCC patients. The online version of this article (doi:10.1186/s12885-015-1826-4) contains supplementary material, which is available to authorized users

  9. Preliminary study of molecular imaging of human hepatocellular carcinoma xenograft with Gd-based MR probe containing arginine-glycine-aspartic acid chelate

    International Nuclear Information System (INIS)

    Huo Tianlong; Du Xiangke; Zhang Sen; Li Xubin; Liu Xia

    2008-01-01

    Objective: To develop a Gd-based MR probe containing arginine-glycine-aspartic acid (RGD) motif to reveal integrin αvβ3 receptor-expressed tumor. Methods: Commercially available HYNIC- RGD conjugate with co-ligand EDDA was labeled with GdCl 3 , and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA-HYNIC-RGD. Human HCC cell line BEL-7402 was cultured and the cells harvested and suspended then subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin αcβ3 receptor and cell viability experiments were conducted. Then in vivo, imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at baseline and time points of 0, 30, 60, 90 minutes and 24 hour post-intravenous injection (p. i.) via the tail vein. Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA-HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The T 1 relaxation rate of the probe is 3.31 mmol/s; It is well tolerated to living cells when the concentration of the probe is below 0.1 μmol/ml; both BEL-7402 Human Hepatocellular Carcinoma cell line and the tumor expressed αvβ3 receptor; The RGD-ligand was observed specifically binding with αvβ3 receptor in vitro; The nude mice model bearing HHCC was well established. The signal intensity (SI) at the tumor site were 2247.6±39.0 at baseline and 2820.9±35.2 at 90 min p.i. respectively, the SI at 90 min increased less than 25% of baseline, which is statistically different (t=-38.031, P 0.05); The signal to time curve for probe-administrated group is straightforward over time in the span of 0 to 90 minute p.i. while the control arms do not show such tendency. Conclusion: Gd-EDDA-HYNIC-RGD has the potential to used as an MR probe detecting integrin αvβ3 receptor-expressed tumor

  10. Unilateral cervical nodal metastasis is an independent prognostic factor for esophageal squamous cell carcinoma patients undergoing chemoradiotherapy: a retrospective study.

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    Full Text Available To determine the prognostic significance of unilateral cervical lymph nodal metastasis (CLNM in patients with inoperable thoracic esophageal squamous cell carcinoma (SCC and to identify significant prognostic factors in these patients.This retrospective study involved 395 patients with inoperable esophageal SCC treated with concurrent chemoradiotherapy. The patients were classified into three groups according to their cervical lymph node status: group A, no evidence of CLNM; group B, unilateral CLNM; group C, other distant metastases. Overall survival (OS and progression-free survival (PFS were calculated. Significant prognostic factors were identified using univariate and multivariate analyses.The 3-year OS rates in groups A, B and C were 46.7%, 33.5% and 8.3%, respectively (p<0.001, log-rank test. The corresponding PFS rates were 40.7%, 26.4% and 4.7% (p<0.001, log-rank test. Group B had a similar prognosis to that of group A and better 3-year OS (p = 0.009 and PFS (p = 0.006 rates than those of group C. Multivariate analysis demonstrated that T stage, chemotherapy regimen and cervical lymph node involvement were independent prognostic factors affecting OS and PFS.Compared to other distant metastases, unilateral CLNM is associated with longer OS in esophageal SCC and should be regarded as a regional disease. Sex, T stage, concurrent chemotherapy modality and cervical lymph node involvement are independent predictors of survival in esophageal SCC.

  11. Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix

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    Gupta Ruchi

    2010-01-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC which has not been reported in the Indian population previously. Materials and Methods: Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12. Statistical Analysis: For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe. Results: p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20. There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20% showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001. Conclusions: p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.

  12. Kidney-Sparing Methods for Extended-Field Intensity-Modulated Radiotherapy (EF-IMRT) in Cervical Carcinoma Treatment.

    Science.gov (United States)

    Kunogi, Hiroaki; Yamaguchi, Nanae; Terao, Yasuhisa; Sasai, Keisuke

    2016-01-01

    Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction.

  13. Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells.

    Science.gov (United States)

    Batman, Gavin; Oliver, Anthony W; Zehbe, Ingeborg; Richard, Christina; Hampson, Lynne; Hampson, Ian N

    2011-01-01

    We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism. SiHa cervical carcinoma cells were stably transfected with the proteasome sensor vector pZsProSensor-1 to confirm lopinavir inhibits the proteasome in these cells. The Panorama Xpress profiler 725 antibody array was then used to analyse specific changes in protein expression in lopinavir-treated versus control untreated SiHa cells followed by PCR and western blotting. Colorimetric growth assays of lopinavir-treated E6/E7 immortalised versus control human keratinocytes were performed. Targeted small interfering RNA gene silencing followed by growth assay comparison of lopinavir-treated/untreated SiHa cells was also used. Lopinavir induced an increase in the fluorescence of pZsProSensor-1 transfected SiHa cells, indicative of proteasomal inhibition. Ribonuclease L (RNASEL) protein was shown to be up-regulated in lopinavir-treated SiHa cells, which was confirmed by PCR and western blot. Targeted silencing of RNASEL reduced the sensitivity of SiHa cells to lopinavir. Selective toxicity against E6/E7 immortalised keratinocytes versus control cells was also seen with lopinavir and was associated with up-regulated RNASEL expression. These data are consistent with the toxicity of lopinavir against HPV-positive cervical carcinoma cells being related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein RNASEL. This is supported by the drug's selective toxicity and up-regulation of RNASEL in E6/E7 immortalised keratinocytes combined with the increased resistance to lopinavir observed in SiHa cells following silencing of RNASEL gene expression.

  14. Clinical impact of FDG PET-CT on the management of patients with locally advanced cervical carcinoma

    International Nuclear Information System (INIS)

    Fleming, S.; Cooper, R.A.; Swift, S.E.; Thygesen, H.H.; Chowdhury, F.U.; Scarsbrook, A.F.; Patel, C.N.

    2014-01-01

    Aim: To evaluate the impact of staging FDG PET-CT on the initial management of patients with locally advanced cervical carcinoma (LACC) and any prognostic variables predicting survival. Materials and methods: Retrospective analysis of consecutive patients undergoing FDG PET-CT for staging of LACC in a single tertiary referral centre, between April 2008 and August 2011. Comparison was made between MRI and PET-CT findings and any subsequent impact on treatment intent or radiotherapy planning was evaluated. Results: Sixty-three patients underwent FDG PET-CT for initial staging of LACC. Major impact on management was found in 20 patients (32%), a minor impact in five (8%), and no impact in 38 (60%). In those patients where PET-CT had a major impact, 12 had more extensive local nodal involvement, five had occult metastatic disease, two had synchronous tumours, and one patient had equivocal lymph nodes on MRI characterized as negative. PET-positive nodal status at diagnosis was found to be a statistically significant predictor of relapse-free survival (p < 0.05). Conclusion: Staging FDG PET-CT has a major impact on the initial management of approximately one-third of patients with LACC by altering treatment intent and/or radiotherapy planning. PET-defined nodal status is a poor prognostic indicator. - Highlights: • Cervical carcinoma is one of the commonest cancers in women worldwide. • Locally advanced cervical carcinoma is usually treated with chemo-radiotherapy. • FDG PET-CT can have a major impact on management in up to one-third of patients. • It may alter treatment intent or radiotherapy-planning by detecting occult disease. • PET nodal status at diagnosis is an important predictor of relapse-free survival

  15. Undetected human papillomavirus DNA and uterine cervical carcinoma. Association with cancer recurrence

    International Nuclear Information System (INIS)

    Okuma, Kae; Yamashita, Hideomi; Nakagawa, Keiichi; Yokoyama, Terufumi; Kawana, Kei

    2016-01-01

    The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness. A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival. HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ± 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009). In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment. (orig.) [de

  16. Je-Chun-Jun induced apoptosis of human cervical carcinoma HeLa cells

    Institute of Scientific and Technical Information of China (English)

    Han-jung CHAE; Kyung-mi PARK; Geun-youn LEE; Gi-seup JEONG; Hyung-rae PARK; Hyung-min KIM; Soo-wan CHAE; Shim-keun YOO; Hyung-ryong KIM

    2004-01-01

    AIM: To study the mechanism of Je-Chun-Jun (JCJ)-inducing the apoptosis of the human cervical carcinoma,HeLa cells. METHODS: The cell viability was assessed using MTT assay. The optical density was measured at 570 nm. The caspase activity was measured using 50 mmol/L of fluorogenic substrate, AC-DEVD-AMC (caspase3), AC-VEID-AMC (caspase-8) or AC-LEHD-AFC (caspase-9). To confirm the expression of proteins, Western blotting was performed. To detect the characteristic of apoptosis chromatin condensation, HeLa cells were stained with Hoechst 33258 in the presence of JCJ. For the cell cycle analysis, HeLa cells were incubated with Propidium iodide (PI) solution. Fluorescence intensity of cell cycle was measured using flow cytometry system. RESULTS:The loss of viability occurred following the exposure of 10 g/L JCJ. Cells treated with 10 g/L JCJ for 3 d exhibited the apoptotic morphology (brightly blue-fluorescent condensed nuclei by Hoechst 33258-staining) and the reduction of cell volume. Cells incubated with JCJ for 48 h were arrested at the G1 phase of cell cycle and their G1 checkpoint related gene products such as cyclin D1 were transiently decreased. We showed that JCJ induced the p38 MAPK activation in HeLa cells. The p38 MAPK inhibitor, SB203580 protected Hela cells from the JCJ-induced death as well as intervened the JCJ-induced accumulation of cells at the G1 phase. In contrast, MEK1 (-ERK upstream) inhibitor, PD98059 had no effect on HeLa cells. CONCLUSION: JCJ induced cell cycle arrest and apoptosis of HeLa cells through p38 MAPK pathway.

  17. Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure

    OpenAIRE

    Hompland Tord; Ellingsen Christine; Rofstad Einar K

    2012-01-01

    Abstract Background High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as c...

  18. A novel functional site of extracellular matrix metalloproteinase inducer (EMMPRIN) that limits the migration of human uterine cervical carcinoma cells.

    Science.gov (United States)

    Sato, Takashi; Watanabe, Mami; Hashimoto, Kei; Ota, Tomoko; Akimoto, Noriko; Imada, Keisuke; Nomizu, Motoyoshi; Ito, Akira

    2012-01-01

    EMMPRIN (extracellular matrix metalloproteinase inducer)/CD147, a membrane-bound glycoprotein with two extracellular loop domains (termed loops I and II), progresses tumor invasion and metastasis by increasing the production of matrix metalloproteinase (MMP) in peritumoral stoma cells. EMMPRIN has also been associated with the control of migration activity in some tumor cells, but little is known about how EMMPRIN regulates tumor cell migration. In the present study, EMMPRIN siRNA suppressed the gene expression and production of EMMPRIN in human uterine cervical carcinoma SKG-II cells. An in vitro scratch wound assay showed enhancement of migration of EMMPRIN-knockdown SKG-II cells. In addition, the SKG-II cell migration was augmented by adding an E. coli-expressed human EMMPRIN mutant with two extracellular loop domains (eEMP-I/II), which bound to the cell surface of SKG-II cells. However, eEMP-I/II suppressed the native EMMPRIN-mediated augmentation of proMMP-1/procollagenase-1 production in a co-culture of the SKG-II cells and human uterine cervical fibroblasts, indicating that the augmentation of SKG-II cell migration resulted from the interference of native EMMPRIN functions by eEMP-I/II on the cell surface. Furthermore, a systematic peptide screening method using nine synthetic EMMPRIN peptides coding the loop I and II domains (termed EM1-9) revealed that EM9 (170HIENLNMEADPGQYR184) facilitated SKG-II cell migration. Moreover, SKG-II cell migration was enhanced by administration of an antibody against EM9, but not EM1 which is a crucial site for the MMP inducible activity of EMMPRIN. Therefore, these results provide novel evidence that EMMPRIN on the cell surface limits the cell migration of human uterine cervical carcinoma cells through 170HIENLNMEADPGQYR184 in the loop II domain. Finally, these results should provide an increased understanding of the functions of EMMPRIN in malignant cervical carcinoma cells, and could contribute to the development of

  19. [Surrogate mothers and ovarian transposition: two attitudes to be considered in young women with cervical carcinoma. A case report].

    Science.gov (United States)

    Giacalone, P L; Sobierajksi, J; Benos, P; Giovannini, N; Laffargue, F; Hédon, B

    2003-02-01

    In cases of cervical cancer, there are 2 major advantages to preserving the ovaries, with or without transposition: hormone function is maintained during subsequent cancer treatment and patient quality of life is improved. We report the first case of pregnancy in a surrogate mother following stimulation of a transposed ovary before irradiation and chemotherapy for a squamous cell carcinoma of the uterine cervix. Because of the wide dissemination of information on the technical progress in this area, patients are now in a position to make therapeutic choices that are no longer guided by strictly medical considerations.

  20. Retrospective case-control study of surgical treatment of stage IB-IIA cervical carcinomas after neoadjuvant radiotherapy

    International Nuclear Information System (INIS)

    Cigriejiene, V. M.; Kajenas, S.; Balnys, M.; Mikuckaite, L.

    2004-01-01

    To evaluate if preoperative radiotherapy influences course of operation (radical hysterectomy and lymphadenectomy) and postoperative period in series of stage IB-IIA cervical carcinomas. Retrospective comparative study was performed. During the study we analyzed 101 case histories of patients who underwent radical type II hysterectomy with lymphadenectomy in Kaunas University of Medicine Hospital and Kaunas Hospital of Oncology between 1995 and 2002. Mean operation time was shorter, hemoglobin and hematocrit values after operation were better, stay in hospital was longer, demand for narcotic analgetics was bigger, function of ovaries was maintained more rarely (p 0.05). In our study, preoperative radiotherapy did not seem to complicate course of radical hysterectomy. (author)

  1. Correlation between expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and cervical lymph node metastasis of nasopharyngeal carcinoma.

    Science.gov (United States)

    Huang, Tian; Chen, Mao-Huai; Wu, Ming-Yao; Wu, Xian-Ying

    2013-03-01

    We evaluated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-2 (MMP-2) in nasopharyngeal carcinoma (NPC) and studied their relationship with cervical lymph node metastasis. Immunohistochemical staining was used to detect the expression of EMMPRIN and MMP-2 in specimens from patients with chronic nasopharyngitis (CN), nonmetastastic NPC (NM-NPC), and lymph node-metastatic NPC (LNM-NPC). The rates of positive EMMPRIN expression in CN, NM-NPC, and LNM-NPC were 13.3%, 30.0%, and 66.7%, respectively. Significant differences were found between the rates in CN and LNM-NPC (p correlated (rs = 0.466; p <0.01). Nasopharyngeal carcinoma cells may attain enhanced metastastic capability through the expression of MMP-2 induced by EMMPRIN.

  2. Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

    International Nuclear Information System (INIS)

    Ivanova, Tatiana A; Golovina, Daria A; Zavalishina, Larisa E; Volgareva, Galina M; Katargin, Alexey N; Andreeva, Yulia Y; Frank, Georgy A; Kisseljov, Fjodor L; Kisseljova, Natalia P

    2007-01-01

    High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16 ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16 ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16 ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16 ink4a was analyzed by RT-PCR and by immunohistochemical technique. The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16 ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective

  3. The surgical treatment of failure in cervical lymph nodes after radiotherapy for nasopharyngeal carcinoma: an analysis of 83 patients

    International Nuclear Information System (INIS)

    Gu Wendong; Ji Qinghai; Lu Xueguan; Feng Yan

    2003-01-01

    Objective: To analyze the results of neck dissection in patients who failed in cervical lymph nodes after radiotherapy for nasopharyngeal carcinoma. Methods: Eighty-three patients who received neck dissection due to lymph node persistence or recurrence after definitive radiotherapy were analyzed retrospectively according to the following relevant factors: age, sex, the interval between completion of radiotherapy and surgery, rN stage, postoperative radiotherapy given or not, the adjacent tissues involved or not and the number of positive nodes. Kaplan-Meier method, Log-rank method and Cox method were used in the statistical analysis. Results: The 1-, 3- and 5-year overall survival rates were 80.7%, 47.1% and 34.9%. The interval between completion of radiotherapy and surgery, postoperative radiotherapy given or not, the adjacent tissues involved or not were significantly prognostic factors in statistic analysis. Conclusions: Neck dissection can be applied in the management of cervical lymph node failure in nasopharyngeal carcinoma after radiotherapy. Postoperative radiotherapy should be considered in patients with capsular invasion and/or adjacent tissue involvement

  4. Ultrasound-guided interstitial brachytherapy in the treatment of advanced vaginal recurrences from cervical and endometrial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Weitmann, H.D.; Knocke, T.H.; Waldhaeusl, C.; Poetter, R. [Dept. of Radiotherapy and Radiobiology, Medical Univ. of Vienna (Austria)

    2006-02-01

    Background: in advanced vaginal recurrences of cervical and endometrial carcinomas therapeutic options are rare because of preceding therapy. Patients and methods: 23 patients developing advanced vaginal recurrences of cervical and endometrial carcinomas were included. 15 patients started with external-beam therapy to the pelvis and eight patients after preceding radiotherapy underwent brachytherapy alone. All patients had ultrasound-guided implantation of transvaginal or transperineal interstitial needles for brachytherapy. Median prescribed total dose was 64 Gy. Results: 18 patients (78%) achieved complete remission. Six patients are alive without tumor and one with tumor after a median follow-up of 64 months. 14 patients died of tumor and two of intercurrent disease. 5-year disease-specific survival and local control rate were 43% and 47%, respectively, in patients with complete remission. Univariate analysis found time to relapse > 2 years, initial diameter {<=} 4 cm, initial volume < 15 cm{sup 3}, no extension to the pelvic side wall, volume before brachytherapy < 7.5 cm{sup 3}, brachytherapy coverage index > 0.8, and prescribed total dose > 64 Gy being positive predictors for local control and survival. Conclusion: the use of ultrasound guidance for placement of interstitial needles in template-based brachytherapy of advanced recurrent gynecologic malignancies is a feasible, safe, and cheap method with encouraging results. Today, ultrasound imaging can be also used to some extent for treatment planning which requires further development. Patient- and treatment-related prognostic factors can be defined. (orig.)

  5. Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery

    International Nuclear Information System (INIS)

    Haasbeek, Cornelis J.A.; Uitterhoeve, Apollonia L.J.; Velden, Jacobus van der; Gonzalez, Dionisio Gonzalez; Stalpers, Lukas J.A.

    2008-01-01

    Abstarct: Background and purpose: Tumor recurrence after surgery for cervical carcinoma is associated with high fatality and morbidity, forming a major therapeutic challenge. This paper presents our experience with treatment of this patient group by salvage radiotherapy with curative intent. Materials and methods: Thirty-five patients with a pelvic recurrence after hysterectomy received high-dose radiotherapy. A retrospective analysis of long-term outcome and prognostic factors was performed. Results: After a median follow-up period of 12.1 years, actuarial 2-,5- and 10-year overall survival rates were 66%, 43% and 33%; disease-free survival rates were 62%, 45% and 41%, respectively. Pelvic control rates at 2-,5- and 10-years were 77%, 69% and 62%. Unfavorable prognostic factors on univariate analysis for survival were: recurrence extending to the pelvic wall versus central recurrence, early recurrence after surgery, external boost versus brachytherapy boost, low total dose and high age. Only a brachytherapy boost and a long interval between surgery and recurrence were significant on multivariate analysis. Severe complications (≥grade 3) were seen in 6 patients (17%; actuarial after 5 years, 21%). Conclusions: Salvage radiotherapy for recurrent cervical carcinoma following surgery may result in 40-50% long-term disease-free survival and an acceptable risk of severe treatment complications, even in patient with recurrences extending to the pelvic wall

  6. A Lentinus edodes polysaccharide induces mitochondrial-mediated apoptosis in human cervical carcinoma HeLa cells.

    Science.gov (United States)

    Ya, Guowei

    2017-10-01

    In this study, a homogeneous polysaccharide (LEP1) with an average molecular weight of 53kDa was successfully purified from the fruiting bodies of Lentinus edodes and its anticancer efficacy on human cervical carcinoma HeLa cells in vitro and associated possible molecular mechanism were also evaluated. MTT assay showed that LEP1 exhibited a dose-dependent inhibitory effect on the proliferation of HeLa cells and caused apoptotic death. Our present findings provided the first evidence that LEP1 induced the apoptosis of HeLa cells via a mitochondria dependent pathway, as indicated by an increase in Bax/Bcl-2 ratio, a loss of mitochondrial membrane potential (Δym), the release of cytochrome c from the mitochondria to the cytosol, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP) in HeLa cells. These combined results unequivocally indicated that the involvement of mitochondria-mediated signaling pathway in LEP1-induced apoptosis and strongly provided experimental evidence for the use of LEP1 as a potential therapeutic agent in the prevention and treatment of human cervical carcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Low Doses of Gamma Rays Reduce the Sensitivity of Cervical Carcinoma Cells to Subsequent Treatment with Cisplatin

    International Nuclear Information System (INIS)

    Osmak, M.; Brozovic, A.

    2003-01-01

    One of the major challenges of modern genetics is to apply recent advances in mutation research to improve the accuracy of the estimates of the genetic risk for humans. Because of the important implications for radiation protection, biological effects of low-dose radiation have been a focus of research in recent years. Previously we have found that human cervical carcinoma HeLa cells irradiated repeatedly with low doses of gamma rays (HeLa1500 cells) became resistant to cisplatin. In this study we examine whether this effect was caused by inhibition of apoptosis. In HeLa and HeLa1500 cells we determined the induction of apoptosis following the treatment with cisplatin (i) by counting apoptotic cells with characteristic morphological changes, (ii) by analysing the expression of apoptotic genes involved in cytochrome c/Apaf-1/caspase-9 and in Fas/FasL pathways by Western blot method, and (iii) by estimating the activities of caspases by commercial caspase detection kits. Our results show that low doses of gamma rays induced alterations in human cervical carcinoma cells that were reflected in inhibition of p53-independent cisplatin-induced apoptosis due to reduced activity of caspase 3. (author)

  8. Monitoring early response to anti-angiogenic therapy: diffusion-weighted magnetic resonance imaging and volume measurements in colon carcinoma xenografts.

    Directory of Open Access Journals (Sweden)

    Moritz Jörg Schneider

    Full Text Available OBJECTIVES: To evaluate the use of diffusion-weighted MRI (DW-MRI and volume measurements for early monitoring of antiangiogenic therapy in an experimental tumor model. MATERIALS AND METHODS: 23 athymic nude rats, bearing human colon carcinoma xenografts (HT-29 were examined before and after 6 days of treatment with regorafenib (n = 12 or placebo (n = 11 in a clinical 3-Tesla MRI. For DW-MRI, a single-shot EPI sequence with 9 b-values (10-800 s/mm2 was used. The apparent diffusion coefficient (ADC was calculated voxelwise and its median value over a region of interest, covering the entire tumor, was defined as the tumor ADC. Tumor volume was determined using T2-weighted images. ADC and volume changes between first and second measurement were evaluated as classifiers by a receiver-operator-characteristic (ROC analysis individually and combined using Fisher's linear discriminant analysis (FLDA. RESULTS: All ADCs and volumes are stated as median±standard deviation. Tumor ADC increased significantly in the therapy group (0.76±0.09×10(-3 mm2/s to 0.90±0.12×10(-3 mm2/s; p<0.001, with significantly higher changes of tumor ADC than in the control group (0.10±0.11×10(-3 mm2/s vs. 0.03±0.09×10(-3 mm2/s; p = 0.027. Tumor volume increased significantly in both groups (therapy: 347.8±449.1 to 405.3±823.6 mm3; p = 0.034; control: 219.7±79.5 to 443.7±141.5 mm3; p<0.001, however, the therapy group showed significantly reduced tumor growth (33.30±47.30% vs. 96.43±31.66%; p<0.001. Area under the curve and accuracy of the ADC-based ROC analysis were 0.773 and 78.3%; and for the volume change 0.886 and 82.6%. The FLDA approach yielded an AUC of 0.985 and an accuracy of 95.7%. CONCLUSIONS: Regorafenib therapy significantly increased tumor ADC after 6 days of treatment and also significantly reduced tumor growth. However, ROC analyses using each parameter individually revealed a lack of accuracy in discriminating between therapy and

  9. Combination of neck dissection for cervical metastasis and irradiation of primary tumors for carcinomas of the mesopharynx, hypopharynx, and larynx

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Takahashi, Sugata; Watanabe, Jun; Tomita, Masahiko

    2006-01-01

    Carcinomas of the mesopharynx, hypopharynx, and larynx with early-stage primary tumor and with cervical lymph node metastasis, were treated by neck dissection for cervical metastasis and definitive irradiation of the primary tumor. In this study, the primary sites of the 16 cases were the mesopharynx (10), the hypopharynx (3), and the larynx (3). Twelve cases of early T stages (T1 or T2) and 15 cases of advanced N stages (N2 or N3) were chosen for this treatment concept. Neck lesions were controlled in all cases and all the primary tumors showed complete response at the end of the initial treatment. One case of mesopharyngeal cancer died due to recurrence of the primary tumor and one case of hypopharyngeal cancer died due to complicated lung cancer. The treatment modality for cases of early primary cancer and advanced cervical lymph node metastasis requires well-balanced strategies for both lesions. In these cases, optimal prognosis was obtained because of careful patient selection. The treatment strategy described in this paper should be considered for cases of early T tumors and advanced N tumors. (author)

  10. Efficacy of {sup 18}F-FDG PET/CT in the evaluation of patients with recurrent cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Mittra, Erik; Rodriguez, Cesar A.; Quon, Andrew; Ross McDougall, I.; Iagaru, Andrei [Stanford Hospitals and Clinics, Division of Nuclear Medicine, Stanford, CA (United States); El-Maghraby, Tarek [Cairo University, Nuclear Medicine, Cairo (Egypt); Saad Specialist Hospital, Nuclear Medicine, Al Khobar (Saudi Arabia); Gambhir, Sanjiv S. [Stanford Hospitals and Clinics, Division of Nuclear Medicine, Stanford, CA (United States); Stanford Hospital and Clinics, Division of Nuclear Medicine, Departments of Radiology and Bioengineering, Stanford, CA (United States)

    2009-12-15

    Only a limited number of studies have evaluated the efficacy of {sup 18}F-FDG PET/CT for recurrent cervical carcinoma, which this study seeks to expand upon. This is a retrospective study of 30 women with cervical carcinoma who had a surveillance PET/CT after initial therapy. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated using a 2 x 2 contingency table with pathology results (76%) or clinical follow-up (24%) as the gold standard. The Wilson score method was used to perform 95% confidence interval estimations. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for the detection of local recurrence at the primary site were 93, 93, 93, 86, and 96%, respectively. The same values for the detection of distant metastases were 96, 95, 95, 96, and 95%, respectively. Seventy-one percent of the scans performed in symptomatic patients showed true-positive findings. In comparison, 44% of scans performed in asymptomatic patients showed true-positive findings. But, all patients subsequently had a change in their management based on the PET/CT findings such that the effect was notable. The maximum standardized uptake value ranged from 5 to 28 (average: 13 {+-} 7) in the primary site and 3 to 23 (average: 8 {+-} 4) in metastases which were significantly different (p = 0.04). This study demonstrates favorable efficacy of {sup 18}F-FDG PET/CT for identification of residual/recurrent cervical cancer, as well as for localization of distant metastases. (orig.)

  11. FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement.

    Science.gov (United States)

    Brooks, Frank J; Grigsby, Perry W

    2013-12-23

    Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally

  12. FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement

    International Nuclear Information System (INIS)

    Brooks, Frank J; Grigsby, Perry W

    2013-01-01

    Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally

  13. Development of an in vitro chemo-radiation response assay for cervical carcinoma.

    Science.gov (United States)

    Monk, Bradley J; Burger, Robert A; Parker, Ricardo; Radany, Eric H; Redpath, Leslie; Fruehauf, John P

    2002-11-01

    To determine if synergistic effects of radiation (RT) and chemotherapy (chemo) on human cervical carcinoma cell lines and fresh tumor explants could be determined using an in vitro assay. In vitro radiation response was determined for 4 cell lines and 26 fresh tumor explants in an agar-based assay. Cells were exposed to increasing doses of RT with or without cisplatin (CDDP), carmustine (BCNU), buthionine sulfoximine (BSO), or paclitaxel (Tax). Cell suspensions were cultured for 5 days, with [(3)H]thymidine added on day 3 and proliferation was measured. Results were reported as the fraction of proliferation compared to control (FC). For each combination of irradiation and drug, synergy was tested using the Chou analysis, where a combination index (CI) value of >0.7 indicated cross-resistance. RT dose-dependent proliferation inhibition was observed for 2 of the 4 cell lines, and for all but 1 of the fresh specimens. Significant heterogeneity of tumor response to RT was seen. Four specimens that were 1 standard deviation below the median FC response after exposure to 300 cGy were classified as extremely radiation resistant. Twenty-one tumors were evaluated for synergistic response using the combination of chemo and RT with a median FC of 0.27 (+/-0.27) for 6.0 Gy of RT alone, 0.22 (+/-0.21) for CDDP alone, and 0.05 (+/-0.08) for the combination. A CI of 0.35 and an R value of 0.09 demonstrated synergy between chemo and RT without cross-resistance. Similar synergy without cross-resistance was found for RT in combination with BCNU, BSO, and TAX. Heterogeneous RT dose-response relationships in the in vitro assay were demonstrated. Explants were more sensitive to RT than cell lines. Unlike cell lines, fresh tumor cells consistently displayed synergy with RT and chemo. The synergy between RT and BSO suggests that glutathione depletion may enhance the effect of RT. The assay was feasible for examining fresh tumors and may be an important tool for studying RT or drug

  14. Combined detection of Twist1, Snail1 and squamous cell carcinoma antigen for the prognostic evaluation of invasion and metastasis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Yang, Huilun; Hu, Haiyang; Gou, Yanling; Hu, Yuhong; Li, Hui; Zhao, Hongwei; Wang, Beidi; Li, Peiling; Zhang, Zongfeng

    2018-04-01

    Cervical cancer is one of the most common malignant tumours of the female reproductive system, ranking second only to breast cancer in morbidity worldwide. Essential features of the progression of cervical cancer are invasion and metastasis, which are closely related to disease prognosis and mortality rate. At the present time there is no effective method to evaluate cancer invasion and metastasis before surgery. Here we report our study on molecular changes in biopsy tissue for the prognostic evaluation of cancer invasion and metastasis. Expression of the epithelial-mesenchymal transition-inducing transcription factors Twist1 and Snail1 was detected by immunohistochemistry in 32 normal, 36 low-grade squamous intraepithelial neoplasia (LSIL), 54 high-grade squamous intraepithelial neoplasia (HSIL) and 320 cervical squamous cell carcinoma (CSCC) samples. The correlation between the expression of Twist1, Snail1 and squamous cell carcinoma antigen (SCCA) in CSCC tissues and clinical pathology results was evaluated. A transwell migration and invasion assay was used to explore the roles of Twist1 and Snail1 in the invasion of cancer cells. Lymph node metastasis and lymphovascular space invasion (LVSI) rates for the following groups were analysed: SCCA(+) group, Twist1(+) group, Snail1(+) group, Twist1(+)Snail1(+)group, Twist1(+)SCCA(+)group, Snail1(+)SCCA(+)group and Twist1(+)Snail1(+)SCCA(+) group. The expression of Twist1 and Snail1 was significantly upregulated in HSIL and CSCC (p  0.05). The expression of SCCA was associated with LVSI, lymph node metastasis, FIGO stage and histological grade (p  0.05). Twist1 was an independent factor contributing to the invasion ability of cervical cancer cells. In addition, the positive rate of lymph node metastasis and LVSI was higher in the Twist1(+)Snail1(+)SCCA(+) group than in the SCCA(+) group, Twist1(+) group and Snail1(+) group, respectively (p < 0.05). Combined detection of Twist1 and Snail1 in SCCA-positive biopsy

  15. Hypoxic versus normoxic external-beam irradiation of cervical carcinoma combined with californium-252 neutron brachytherapy. Comparative treatment results of a 5-year randomized study

    Czech Academy of Sciences Publication Activity Database

    Tačev, T.; Vacek, Antonín; Ptáčková, B.; Strnad, V.

    2005-01-01

    Roč. 181, č. 5 (2005), s. 273-284 ISSN 0179-7158 Institutional research plan: CEZ:AV0Z50040507 Keywords : cervical carcinoma * hypoxyradiotherapy * californium-252 Subject RIV: BO - Biophysics Impact factor: 3.490, year: 2005

  16. Genetic immunization against cervical carcinoma : induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7

    NARCIS (Netherlands)

    Daemen, T; Pries, F; Bungener, L; Kraak, M; Regts, J; Wilschut, J

    infection of genital epithelial cells with human papillomavirus (HPV) types 16 and 18 is closely associated with the development of cervical carcinoma. The transforming potential of these high-risk HPVs depends on the expression of the E6 and E7 early viral gene products. Since the expression of E6

  17. Tafazzin (TAZ promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis.

    Directory of Open Access Journals (Sweden)

    Mei Chen

    Full Text Available Tafazzin (TAZ is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27, high-grade squamous intraepithelial lesions (HSIL, n = 26 and squamous cervical carcinoma (SCC, n = 41 by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

  18. Clinical assessment of the response of metastatic cervical lymph nodes to radiation in patients with squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sekiguchi, Kenji

    1985-01-01

    Between November 1981 to May 1985, measurements were made of the exponential regression of 69 cervical nodes from 37 patients with squamous cell carcinoma treated with radiotherapy in the division of clinical oncology, the department of Radiology at the Tokyo Women's Medical College. The volume-halving time (T 1/2(V)) which was calculated in each case was analysed. The results were as follows. 1. T 1/2(V) of oral cavity, lung, hypopharynx and esophagus seemed to be longer than those of oropharynx, uterus, larynx and epipharynx. 2. T 1/2(V) of well differentiated squamous cell carcinoma seemed to be shorter than those of moderately and poorly differentiated squamous cell carcinoma, however no significant difference was found. 3. There were two patterns of initial regression. One half of lymph nodes regressed with an initial shoulder and the other half regressed without it. And T 1/2(V) of regression curve with it was statistically shorter than that without it. 4. There was no significant correlation between T 1/2(V) and the lymph node size. 5. The response rate of lymph node to radiotherapy was higher and the regrowth rate was lower in the fast regression group, compared with those in the slow regression group. (author)

  19. The Value of Diffusion-Weighted Imaging in Combination With Conventional Magnetic Resonance Imaging for Improving Tumor Detection for Early Cervical Carcinoma Treated With Fertility-Sparing Surgery.

    Science.gov (United States)

    Li, Xiulei; Wang, Ling; Li, Yong; Song, Peiji

    2017-10-01

    This study aimed to investigate the value of diffusion-weighted imaging (DWI) in combination with conventional magnetic resonance imaging (MRI) for improving tumor detection in young patients treated with fertility-sparing surgery because of early cervical carcinoma. Fifty-four patients with stage Ia or Ib1 cervical carcinoma were enrolled into this study. Magnetic resonance examinations were performed for these patients using conventional MRI (including T1-weighted imaging, T2-weighted imaging, and dynamic contrast-enhanced MRI) and DWI. The apparent diffusion coefficient (ADC) values of cervical carcinoma were analyzed quantitatively and compared with that of adjacent epithelium. Sensitivity, positive predictive value, and accuracy of 2 sets of MRI sequences were calculated on the basis of histologic results, and the diagnostic ability of conventional MRI/DWI combinations was compared with that of conventional MRI. The mean ADC value from cervical carcinoma (mean, 786 × 10 mm/s ± 100) was significantly lower than that from adjacent epithelium (mean, 1352 × 10 mm/s ± 147) (P = 0.01). When the threshold ADC value set as 1010 × 10 mm/s, the sensitivity and specificity for differentiating cervical carcinoma from nontumor epithelium were 78.2% and 67.2%, respectively. The sensitivity and accuracy of conventional MRI for tumor detection were 76.0% and 70.4%, whereas the sensitivity and accuracy of conventional MRI/DWI combinations were 91.7% and 90.7%, respectively. Conventional MRI/DWI combinations revealed a positive predictive value of 97.8% and only 4 false-negative findings. The addition of DWI to conventional MRI considerably improves the sensitivity and accuracy of tumor detection in young patients treated with fertility-sparing surgery, which supports the inclusion quantitative analysis of ADC value in routine MRI protocol before fertility-sparing surgery.

  20. Matrix Metalloproteinase-2, Squamous Cell Carcinoma Antigen, and Tissue Polypeptide-Specific Antigen Expression in Egyptian Patients with Cervical Carcinoma: Relationship with Prognosis

    Directory of Open Access Journals (Sweden)

    Maha Imam Ahmed

    2004-01-01

    Full Text Available Matrix metalloproteinases (MMPs, a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA, and tissue polypeptide – specific antigen (TPS in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA, we analyzed 50 patients with cervical carcinoma (CC and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR and 95% confidence interval (CI for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9] and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]. Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]. Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach.

  1. Squamous Cell Carcinoma Antigen in Follow-Up of Cervical Cancer Treated With Radiotherapy: Evaluation of Cost-Effectiveness

    International Nuclear Information System (INIS)

    Forni, Franca; Ferrandina, Gabriella; Deodato, Francesco; Macchia, Gabriella; Morganti, Alessio G.; Smaniotto, Daniela; Luzi, Stefano; D'Agostino, Giuseppe; Valentini, Vincenzo; Cellini, Numa; Giardina, Bruno; Scambia, Giovanni

    2007-01-01

    Purpose: The squamous cell carcinoma (SCC) antigen is still considered the most accurate serologic tumor marker in cervical carcinoma. We assessed the contribution of the SCC assay to the detection of recurrences in patients treated with radiotherapy. Methods and Materials: The pattern of recurrence and follow-up data were prospectively recorded for 135 patients. Of the 135 patients, 103 (76.3%) had primary cervical carcinoma and 32 (23.7%) had already experienced disease recurrence that had been successfully treated with surgery (n = 2), surgery plus radiotherapy (n = 2), radiotherapy (n = 5), or concomitant chemoradiotherapy (n = 23). The follow-up evaluations (chest X-ray, abdominopelvic magnetic resonance imaging, gynecologic examination with colposcopy, Papanicolaou smear, and SCC assay) were performed at 6-month intervals; the evaluation was done earlier if recurrent disease was suspected. The median follow-up time was 29 months (range, 6-131). The SCC serum levels were assayed, and a cost analysis was done. Results: A total of 481 SCC determinations were performed. Of the 135 patients, 43 (31.8%) experienced disease recurrence. The SCC levels were higher in those with recurrent disease than in the disease-free patients. Elevation of SCC was documented in 34 (79.1% sensitivity) of 43 recurrences before symptoms appeared. Of the 38 patients with serum SCC elevation, 34 developed a recurrence (positive predictive value, 89.5%). Of the 97 patients with negative SCC serum levels, 88 had negative findings at the clinicoradiologic evaluation (negative predictive value, 90.7%). A simplified approach (SCC plus gynecologic examination) was evaluated. Compared with the complete follow-up program, the rate of missed recurrence was 2.2%. The total projected cost per patient for 5 years of follow-up for the simplified procedure was approximately 12.2-fold lower than the standard approach. Conclusions: Our results have shown that a simplified diagnostic approach, including

  2. The stratification of severity of acute radiation proctopathy after radiotherapy for cervical carcinoma using diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiang Sheng, E-mail: lxsheng500@163.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Fang, Hong, E-mail: hongfang196808@sina.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Song, Yunlong, E-mail: yunlongsong010@sina.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Li, Dechang, E-mail: dechangli1972@sina.com [Department of Pathology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Wang, Yingjie, E-mail: wangyj19710813@sina.com [Department of Radiotherapy, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Zhu, Hongxian, E-mail: hongxian0102@sina.cn [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Meng, Limin, E-mail: liminmeng1977@sina.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Wang, Ping, E-mail: pingwang1978@sina.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Wang, Dong, E-mail: dongwang1964@sina.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China); Fan, Hongxia, E-mail: fanhongxia1975@sina.com [Department of Radiology, Air Force General Hospital of People' s Liberation Army, Beijing 100142 (China)

    2017-02-15

    Objective: To determine whether diffusion-weighted imaging (DWI) can be used for quantitatively evaluating severity of acute radiation proctopathy after radiotherapy for cervical carcinoma. Materials and methods: One hundred and twenty-four patients with cervical carcinoma underwent MR examination including DWI before and after radiotherapy. Acute radiation proctopathy was classified into three groups (grade 0, grade I–II and grade III–IV) according to Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG). The pretreatment ADC (ADC{sub pre}), ADC after treatment (ADC{sub post}) and ADC change (ΔADC) were compared among three groups. In addition, acute radiation proctopathy was classified into good-prognosis group and poor-prognosis group. ADC{sub pre}, ADC{sub post} and ΔADC were compared between two groups. For DWI parameter that had significant difference, discriminatory capability of the parameter was determined using receiver operating characteristics (ROC) analysis. Results: ADC{sub post} and ΔADC were higher in grade I–II group than in grade 0 group (p < 0.05), yielding a sensitivity of 79.3% and specificity of 69.4% for ADC{sub post}, and 85.1%, 72.3% for ΔADC for discrimination between two groups. ADC{sub post} and ΔADC were higher in grade III–IV group than in grade I–II group (p < 0.05), yielding a sensitivity of 80.3% and specificity of 72.5% for ADC{sub post}, and 84.1%, 74.5% for ΔADC for discrimination between two groups. ADC{sub post} and ΔADC were higher in poor-prognosis group than in good-prognosis group (p < 0.05), yielding a sensitivity of 79.5% and specificity of 73.4% for ADC{sub post}, and 87.2%, 78.3% for ΔADC for discrimination between two groups. Conclusion: Diffusion-weighted MRI can be used for quantitative stratification of severity of acute radiation proctopathy, which serves as an important basis for appropriate timely adjustment of radiotherapy for cervical carcinoma in order to maximally reduce the

  3. The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-01-01

    Full Text Available Background: Pelvic lymph node metastasis (LNM is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75-80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs, unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence. Methods: We performed a retrospective review of 296 patients diagnosed with Stage IA-IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People′s Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI, depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy. Results: The incidence of pelvic LNM was 20.27% (60/296 cases. Pelvic LNM (P = 0.00 was significantly correlated with recurrence. Pelvic LNM (P = 0.00, the number of positive pelvic LNs (P = 0.04 and a single group versus multiple groups of pelvic LNM (P = 0.03 had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00, depth of cervical stromal invasion (P = 0.00 and parametrial invasion (P = 0.03 were independently associated with pelvic LNM. Conclusions: Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI

  4. Validade da citologia e da biópsia orientada pela colposcopia no diagnóstico do carcinoma cervical pré-clínico Validity of cytology and colposcopy - guided biopsy for the diagnosis of preclinical cervical carcinoma

    Directory of Open Access Journals (Sweden)

    Aldo Franklin Ferreira Reis

    1999-05-01

    Full Text Available Objetivo: avaliar a eficácia da citologia e da biópsia orientada pela colposcopia na discriminação entre o carcinoma invasor pré-clínico e as lesões intra-epiteliais. Pacientes e Métodos: 441 pacientes submetidas a conização, histerectomia e operação de Wertheim-Meigs, no período de 1978 a 1995, no Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Setor de Patologia Cervical. Foram efetuados os cálculos da sensibilidade, especificidade, valores preditivos, razão de verossimilhança e intervalos de confiança de cada exame, divididos em quatro categorias: normal e inflamatório; displasia leve e displasia moderada; displasia acentuada e carcinoma in situ, e carcinoma microinvasor e invasor. As biópsias foram analisadas como um todo e separadas pelo tipo de colposcopia (satisfatória e insatisfatória. Resultados: a citologia mostrou sensibilidade de 50%, especificidade de 89%, valor preditivo positivo de 63% e valor preditivo negativo de 82%. As razões de verossimilhança foram 4,4 para o diagnóstico de invasão, 0,7 para displasia acentuada e carcinoma in situ, 0,1 para displasia leve e moderada, 2,2 para normal e inflamatório e 0,6 para o conjunto de resultados negativos para invasão. A biópsia orientada pela colposcopia apresentou sensibilidade de 50%, especificidade de 100%, valor preditivo positivo de 100% e valor preditivo negativo de 83%. As razões de verossimilhança foram: tendendo ao ¥ para o resultado de invasão, 0,5 para displasia acentuada e carcinoma in situ, 0,2 para displasia leve e moderada, 0,3 para normal e inflamatório e 0,5 para o conjunto de resultados negativos para invasão. A biópsia orientada pela colposcopia satisfatória com lesão visível mostrou sensibilidade de 59%, especificidade de 100%, valor preditivo positivo de 100% e valor preditivo negativo de 83%. As razões de verossimilhança foram: tendendo ao ¥ para o resultado positivo de invasão, 0

  5. Undetected human papillomavirus DNA and uterine cervical carcinoma. Association with cancer recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Okuma, Kae; Yamashita, Hideomi; Nakagawa, Keiichi [University of Tokyo Hospital, Departments of Radiology, Tokyo (Japan); Yokoyama, Terufumi; Kawana, Kei [University of Tokyo Hospital, Departments Obstetrics and Gynecology, Tokyo (Japan)

    2016-01-15

    The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness. A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival. HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ± 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009). In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment. (orig.) [German] Gegenstand der Untersuchung war der Zeitverlauf der Eliminierung von humaner Papillomvirus-(HPV-)DNA bei Patienten mit Zervixkarzinomen waehrend der Nachfolgeuntersuchungen nach einer primaeren radikalen Strahlentherapie (RT). Diese Studie untersuchte den Zusammenhang zwischen dem Zeitpunkt der

  6. The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma cells.

    Science.gov (United States)

    Kuo, M L; Kunugi, K A; Lindstrom, M J; Kinsella, T J

    1997-01-01

    The results from prior in vitro and in vivo studies and recent phase 3 clinical trials suggest a significant potential role for hydroxyurea (HU) as a clinical radiosensitizer for cervix cancer. However, a detailed study of possible cellular mechanisms of radiosensitization in human cervix cancer cells as a consequence of dose and timing of HU and ionizing radiation (IR) has not been performed. This in vitro study analyses the interactions of HU and IR in a human cervical carcinoma cell line, Caski. Exponentially growing Caski cells were continuously exposed to clinically achievable but minimally cytotoxic concentrations of HU (0.3-3.0 mM) for various time intervals (6, 12, 18, 24, and 30 hours) up to one population doubling time either prior to or immediately following IR (2-8 Gy). The radiation survival data were analyzed using our modification of the linear-quadratic model to test for an interaction (greater than additive). The effects of HU alone, IR alone, and the combination on cell cycle progression and on apoptotic cell death in exponentially growing Caski cells were measured. We report a significant HU-IR interaction (radiosensitization) based on the sequence of HU exposure (post- > pre-IR) and with increasing concentrations of HU (0.3-3.0 mM), but no effect on radiosensitization with the duration of exposure to HU for up to one cell population doubling (6-30 hours). HU concentration has a significant effect on both alpha and beta linear-quadratic values in the post-IR sequences. Exposures of exponentially growing Caski cells to 1 mM and 3 mM HU alone result in a complete block in early S phase throughout the 30-hour exposure, while 0.3 mM HU causes a transient early S-phase block over the initial 12 to 18 hours of exposure. HU alone has no effect on cell cycle progression in G1 or G2/M populations but results in a large apoptotic population (31% following 1 mM HU x 30 hours), which appears to be the principal mechanism of drug cytotoxicity in these cells

  7. A CHILD WITH EPISTAXIS, REDUCED HEARING AND CERVICAL LYMPHADENOPATHY: A RARE CASE OF NASOPHARYNGEAL CARCINOMA IN A CHILD

    Directory of Open Access Journals (Sweden)

    SUHAIMI Y

    2011-01-01

    Full Text Available Although nasopharyngeal carcinoma (NPC is common in this part of the world, the incidence among children is still very low worldwide. The diagnosis is sometimes delayed because of the late reporting of the symptom by the patient or parents, or difficulty in reaching the final diagnosis due to its hidden anatomical location. The challenges include the difficult endoscopy in children, inability to differentiate an adenoid from the tumour on radiograph and often the inconclusive fine needle aspiration findings. If the tumour mass at Fossa of Rosenmuller can be clearly appreciated and biopsied with undoubtedly proven histology of NPC, the diagnosis can be straight forward and treatment can be commenced as early as possible. We report a 10-year-old child presented with bilateral neck cervical lymphadenopathy and epistaxis with fine needle aspiration cytology(FNAC of the neck mass reported as lymphoma. Further work-up confirmed he was suffering from NPC.

  8. Fibroblast Growth Factor Receptor 3 (FGFR3–Analyses of the S249C Mutation and Protein Expression in Primary Cervical Carcinomas

    Directory of Open Access Journals (Sweden)

    Haiyan Dai

    2001-01-01

    Full Text Available Fibroblast growth factor receptor 3 (FGFR3 seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3 gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS, and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8% samples. Six of the tumours (8.2% revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.

  9. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells.

    Science.gov (United States)

    Kim, Dong-Hyun; Jarvis, Roger M; Allwood, J William; Batman, Gavin; Moore, Rowan E; Marsden-Edwards, Emma; Hampson, Lynne; Hampson, Ian N; Goodacre, Royston

    2010-12-01

    It has been shown that the HIV protease inhibitors indinavir and lopinavir may have activity against the human papilloma virus (HPV) type 16 inhibiting HPV E6-mediated proteasomal degradation of p53 in cultured cervical carcinoma cells. However, their mode and site of action is unknown. HPV-negative C33A cervical carcinoma cells and the same cells stably transfected with E6 (C33AE6) were exposed to indinavir and lopinavir at concentrations of 1 mM and 30 μM, respectively. The intracellular distribution of metabolites and metabolic changes induced by these treatments were investigated by Raman microspectroscopic imaging combined with the analysis of cell fractionation products by liquid chromatography-mass spectrometry (LC-MS). A uniform cellular distribution of proteins was found in drug-treated cells irrespective of cell type. Indinavir was observed to co-localise with nucleic acid in the nucleus, but only in E6 expressing cells. Principal components analysis (PCA) score maps generated on the full Raman hypercube and the corresponding PCA loadings plots revealed that the majority of metabolic variations influenced by the drug exposure within the cells were associated with changes in nucleic acids. Analysis of cell fractionation products by LC-MS confirmed that the level of indinavir in nuclear extracts was approximately eight-fold greater than in the cytoplasm. These data demonstrate that indinavir undergoes enhanced nuclear accumulation in E6-expressing cells, which suggests that this is the most likely site of action for this compound against HPV.

  10. Asperlin induces G{sub 2}/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    He, Long; Nan, Mei-Hua [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Oh, Hyun Cheol [College of Medical and Life Sciences, Silla University, 100 Silladaehak-gil, Sasang-gu, Busan 617-736 (Korea, Republic of); Kim, Young Ho [College of Pharmacy, ChungNam National University, Yuseong, Daejeon, 305-764 (Korea, Republic of); Jang, Jae Hyuk [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Erikson, Raymond Leo [Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 (United States); Ahn, Jong Seog, E-mail: jsahn@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Kim, Bo Yeon, E-mail: bykim@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); World Class Institute, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of)

    2011-06-10

    Highlights: {yields} A new anti-cancer effect of an antibiotics, asperlin, is exploited. {yields} Asperlin induced human cervical cancer cell apoptosis through ROS generation. {yields} Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. {yields} Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  11. Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    International Nuclear Information System (INIS)

    He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

    2011-01-01

    Highlights: → A new anti-cancer effect of an antibiotics, asperlin, is exploited. → Asperlin induced human cervical cancer cell apoptosis through ROS generation. → Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. → Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  12. Human papillomavirus distribution in invasive cervical carcinoma in sub-Saharan Africa: could HIV explain the differences?

    Science.gov (United States)

    Ndiaye, Cathy; Alemany, Laia; Ndiaye, Nafissatou; Kamaté, Bakarou; Diop, Yankhoba; Odida, Michael; Banjo, Kunbi; Tous, Sara; Klaustermeier, Jo Ellen; Clavero, Omar; Castellsagué, Xavier; Bosch, F Xavier; Trottier, Helen; de Sanjosé, Silvia

    2012-12-01

    To describe human papillomavirus (HPV) distribution in invasive cervical carcinoma (ICC) from Mali and Senegal and to compare type-specific relative contribution among sub-Saharan African (SSA) countries. A multicentric study was conducted to collect paraffin-embedded blocks of ICC. Polymerase chain reaction, DNA enzyme immunoassay and line probe assay were performed for HPV detection and genotyping. Data from SSA (Mozambique, Nigeria and Uganda) and 35 other countries were compared. One hundred and sixty-four ICC cases from Mali and Senegal were tested from which 138 were positive (adjusted prevalence = 86.8%; 95% CI = 79.7-91.7%). HPV16 and HPV18 accounted for 57.2% of infections and HPV45 for 16.7%. In SSA countries, HPV16 was less frequent than in the rest of the world (49.4%vs. 62.6%; P < 0.0001) but HPV18 and HPV45 were two times more frequent (19.3%vs. 9.4%; P < 0.0001 and 10.3%vs. 5.6%; P < 0.0001, respectively). There was an ecological correlation between HIV prevalence and the increase of HPV18 and the decrease of HPV45 in ICC in SSA (P = 0.037 for both). HPV16/18/45 accounted for two-thirds of the HPV types found in invasive cervical cancer in Mali and Senegal. Our results suggest that HIV may play a role in the underlying HPV18 and HPV45 contribution to cervical cancer, but further studies are needed to confirm this correlation. © 2012 Blackwell Publishing Ltd.

  13. Salvage surgery for hypopharyngeal carcinoma and cervical esophageal carcinoma with local recurrence or residual tumor after chemoradiotherapy

    International Nuclear Information System (INIS)

    Takemura, Hirokazu; Hayashi, Ryuichi; Yamazaki, Mitsuo

    2008-01-01

    In this study, we present the treatment results of salvage surgery in 34 patients with residual primary tumor or local relapse tumor in the hypopharynx and cervical esophagus after radiotherapy (15 patients) or chemoradiotherapy (19 patients) at the Division of Head and Neck Surgery, National Cancer Center Hospital East between 1997 and 2006. All patients underwent total pharyngolaryngoesophagectomy (TPLE) as salvage surgery. Among these patients, postoperative complication was observed in 11 patients (32.4%). Fisher's exact test revealed no significant difference in postoperative complication rate between the radiotherapy (RT) group and chemoradiotherapy (CRT) group. Tumors in the neck recurred in 10 patients (55.6%) after surgical resection. The tumor recurrence control rate for cervical lymph nodes was 84.7% for patients with clinically N0 disease after CRT who had not undergone neck dissection. The median survival time was 392 days. We consider that salvage surgery can he safely performed by considering the necessity and method of operation, and the outcome of patients receiving CRT would he improved by salvage surgery. (author)

  14. Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma

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    Hu YF

    2015-08-01

    Full Text Available Yun-Feng Hu,1 Xia Lei,2 Hong-Yi Zhang,3 Jun-wei Ma,1 Wei-wei Yang,1 Min-lin Chen,1 Jie Cui,1,4 Hong Zhao1 1Department of Oncology, 2Department of Gynecology, 3Department of Urology, Yan’an University Affiliated Hospital, Yan’an, Shaanxi Province, People’s Republic of China; 4Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China Purpose: We aimed to investigate the expression of EGFR and the autophagy-related markers Beclin1 and LC3 in cervical cancer.Methods: Beclin1, LC3, and EGFR expression were analyzed in 80 samples of cervical squamous cell carcinoma (SCC, 40 samples of high-grade cervical intraepithelial neoplasia (CIN, and 40 samples of normal cervical tissues by immunohistochemistry. The protein expression rates were analyzed with χ2 and Fisher’s exact tests. Differences in overall survival (OS were determined using the Kaplan–Meier method and log-rank tests.Results: Cervical cancer, high-grade CIN, and normal cervical epithelial cells expressed Beclin1 in 26.2%, 77.5%, and 82.5% of patients, respectively, and expressed LC3 in 28.8%, 70.0%, and 75.0% of patients, respectively. There was a significant difference between cervical SCC and high-grade CIN or normal cervical epithelial cells (P=0.000. Cervical cancer cells, high-grade CIN cells, and normal cervical epithelial cells expressed EGFR in 68.8%, 62.5%, and 12.5% of patients, respectively. There was a significant difference between cervical SCC or high-grade CIN and normal cervical epithelial cells (P=0.000. No significant association between Beclin1 or LC3 or EGFR expression and various clinicopathological parameters was observed in cervical SCC. There was no significant correlation between Beclin1, LC3, EGFR expression, and 5-year OS rates of cervical SCC patients. Beclin1- or LC3-negativity with EGFR-positivity in cervical SCC was associated with a higher Federation International of

  15. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Stephen Jacques

    2010-01-01

    ABSTRACT: Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18 is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin...... embedded (FFPE) sections of cervical cancer. Tissue blocks from 35 cases of in situ or invasive cervical squamouscell carcinoma and surrogate FFPE sections containing the cell lines HeLa and SiHa were tested for HPV 16 and HPV18 and for the housekeeping gene beta-actin by conventional PCR using type...

  16. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Steven

    2010-01-01

    ABSTRACT: Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18, is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin...... embedded (FFPE) sections of cervical cancer.Tissue blocks from 35 cases of in situ or invasive cervical squamous cell carcinoma and surrogate FFPE sections containing the cell lines HeLa and SiHa were tested for HPV 16 and HPV18 by conventional PCR using type specific primers, and for the housekeeping gene...

  17. CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study.

    Science.gov (United States)

    Tan, Yee Hock; Sidik, Shiran Mohd; Syed Husain, Sharifah Noor Akmal; Lye, Munn Sann; Chong, Pei Pei

    2016-01-01

    Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.

  18. Randomized phase 3 trial comparing 2 cisplatin dose schedules in 326 patients with locally advanced squamous cell cervical carcinoma: long-term follow-up.

    Science.gov (United States)

    Nagy, Viorica Magdalena; Ordeanu, Claudia; Coza, Ovidiu; Alin, Cristian Rancea; Traila, Alexandru; Todor, Nicolae

    2012-11-01

    The evaluation of 5-year results obtained through 2 radiochemotherapy (RCT) regimens: cisplatin (CDDP), 20 mg/m × 5 days every 21 days; and CDDP, 40 mg/m per week in locally advanced cervical carcinoma. In this single-institution prospective randomized phase 3 study, 326 patients with stage IIB to IIIB squamous cell cervical carcinoma treated from March 2003 to March 2005 were included. One hundred sixty patients (49%) had stage IIB cervical carcinoma, 103 patients (31.5%) had stage IIIA cervical carcinoma, and 63 patients (19.5%) had stage IIIB cervical carcinoma. The patients were randomly assigned to 2 therapeutic arms: 164 patients in arm A (5 days) concurrent RCT with CDDP, 20 mg/m per day, days 1 to 5 every 21 days; and 162 patients in arm B (weekly), concurrent RCT with CDDP, 40 mg/m per day weekly. All patients were treated with external beam radiotherapy on the abdominopelvic region using 15-MV x-rays and a cervical boost using the x-rays arch technique or medium-dose-rate intracavitary brachytherapy. The 5-year survival rate obtained through the 2 RCT regimens are not statistically different, even if a tendency of superiority can be observed in the 5-day arm as far as overall survival (78% in arm A vs 72% in arm B; p = 0.14) and disease-free survival (73% in arm A and 69% in arm B; p = 0.09) are concerned. Five-year local relapse-free survival was significantly superior in the 5-day CDDP arm (87%) in comparison with the weekly CDDP arm (77%); p < 0.01. In the 5-day arm, local relapse rate was twice lower, 21/164 (13%), compared with the weekly arm, 40/162 (25%); p < 0.01). Distance failures were identical in the 2 therapeutic groups: 22/164 (13%) and 21/162 (13%), respectively, which shows the superiority of arm A regarding local control. The results of our study demonstrate that RCT with cisplatin, 20 mg/m × 5 days every 21 days, is superior regarding local efficacy and is less toxic compared with the weekly chemotherapy regimen.

  19. Comparative imaging and biodistribution studies with an anti-CEA monoclonal antibody and its F(ab)2 and Fab fragments in mice with colon carcinoma xenografts

    International Nuclear Information System (INIS)

    Andrew, S.M.; Pimm, M.V.; Baldwin, R.W.; Perkins, A.C.

    1986-01-01

    An IgG1 mouse monoclonal antibody directed against CEA has been digested with papain to yield F(ab) 2 and Fab fragments. Following radioiodination, intact antibody and fragments showed specific binding to cells of a CEA-producing tumour, although the immune reactivities of the fragments were lower than that of intact antibody. Gamma scintigraphy of nude mice bearing CEA producing human tumour xenografts and injected with 131 I-labelled fragments showed earlier and superior imaging of tumours than did 131 I-intact antibody, and this was most marked with the Fab fragment. Sequential dissection analyses showed that this was due to earlier and higher tumour-to-blood ratios with fragments than with intact antibody, but in absolute terms the degree of localization of both fragment types was significantly lower than that of intact antibody. (orig.)

  20. Evaluation of fast neutron irradiation in the treatment of squamous cell carcinoma in cervical lymph nodes

    International Nuclear Information System (INIS)

    Duncan, W.; Orr, J.A.; Arnott, S.J.; Jack, W.J.; Kerr, G.R.

    1987-01-01

    Analyses have been made of the response of metastatic cervical lymph nodes following neutron therapy, either as part of a randomized trial or in patients treated electively. In the trial patients, the overall regression and local control rates were similar after photons and neutrons. Mobile nodes, less than 3.0 cm, appeared to respond better to neutron therapy, and node masses greater than 3.0 cm had better control after photon therapy. The differences observed however were not statistically significant. There was a highly significant association between the control of the primary tumor and control of nodal disease. No survival advantage for neutrons was observed in association with apparently better control rates in cervical nodes

  1. Preoperative F-18-FDG PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 whole body scans

    International Nuclear Information System (INIS)

    Byun, Byung Hyun; Urn, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Lee, Byeong Cheol; Lee, Guk Haeng; Lee, Yong Sik; Shim, Youn Sang

    2007-01-01

    We evaluated the diagnostic performance of FDG-PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 scan. All patients had total thyroidectomy and following I-131 ablation therapy. In the follow-up period, FDG-PET showed suspected cervical lymph nodes metastases and neck dissection was performed within 3 months after FDG-PET. It had shown for all patients the negative I-131 scan within 3 months before FDG-PET or negative I-131 scan during the period of cervical lymph nodes metastases suspected on the basis of FDG-PET, CT, or ultrasonography until the latest FDG-PET. Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 19 papillary thyroid carcinoma patients. Serum Tg, TSH, and Tg antibody levels at the time of latest I-131 scan were reviewed. The size of lymph node was measured by preoperative CT or ultrasonography. In 45 cervical lymph node groups dissected, 31 lymph node groups revealed metastasis. The sensitivity and specificity of FDG-PET for metastasis were 74.2% (23 of 31) and 50.0% (7 of 14), respectively. Except for patients with elevated Tg antibody levels, all patients showed the elevated serum Tg levels than normal limits at the TSH of =30uIU/ml. 8 lesions without suspected metastatic findings on FDG-PET revealed metastasis (false negative), and none of them exceeded 8mm in size (4 to 8mm, median= 6mm). On the other hand, 23 true positive lesions on FDG-PET were variable in size (6 to 17mm, median=9mm). FDG-PET is suitable for the detection of metastatic cervical lymph nodes in patients with recurrent papillary thyroid carcinoma. However, false positive or false negative should be considered according to the size of lymph node

  2. Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

    Directory of Open Access Journals (Sweden)

    Frank Georgy A

    2007-03-01

    Full Text Available Abstract Background High risk type human papilloma viruses (HR-HPV induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas Methods Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16ink4a was analyzed by RT-PCR and by immunohistochemical technique. Results The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands. The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. Conclusion Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical

  3. 1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

    Science.gov (United States)

    Lin, Gigin; Lai, Chyong-Huey; Tsai, Shang-Yueh; Lin, Yu-Chun; Huang, Yu-Ting; Wu, Ren-Chin; Yang, Lan-Yan; Lu, Hsin-Ying; Chao, Angel; Wang, Chiun-Chieh; Ng, Koon-Kwan; Ng, Shu-Hang; Chou, Hung-Hsueh; Yen, Tzu-Chen; Hung, Ji-Hong

    2017-03-01

    To assess the clinical value of proton ( 1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. 1 J. Magn. Reson. Imaging 2017;45:899-907. © 2016 International Society for Magnetic Resonance in Medicine.

  4. Comparative study of uptake and washout of 99mTcN(NOEt)2 with 99mTc-MIBI in human cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Xing Shi'an; Zhang Yongxue; An Rui

    2002-01-01

    Objective: to investigate the cellular kinetics of bis (N-ethoxy-N-ethyl dithiocarbamato) nitrido 99m Tc(V) [ 99m TcN (NOEt) 2 ] in human cervical carcinoma cell line Hela and to compare it with that of 99m Tc hexakis-2- methoxyisobutyl isonitrile ( 99m Tc-MIBI), and hence to define the possible clinical value of 99m TcN(NOEt) 2 in tumor imaging. Methods: Using radionuclide tracer technique, 99m TcN(NOEt) 2 and 99m Tc-MIBI were incubated with human cervical carcinoma cell lines Hela at 37 degree C and at 22 degree C respectively. At several incubation times, the uptake and washout characteristics of the radiotracers in human cervical carcinoma cell line Hela were investigated and compared. Results: The maximum uptake of 99m TcN(NOEt) 2 in Hela was 46.15% and that of 99m Tc-MIBI was 12.6% (P 99m TcN(NOEt) 2 after 5 min incubation in human cervical carcinoma cell line Hela was 65% of the total uptake, while that of 99m Tc-MIBI was 50% of the total uptake (P 99m TcN(NOEt) 2 was retained in the Hela cells at one hour while 56.67% of 99m Tc-MIBI was retained (P 99m Tc-MIBI, the cellular kinetics of 99m TcN(NOEt) 2 was not temperature-dependent (the cellular kinetics is similar at 37 degree C and at 22 degree C, P>0.05). Conclusions: In vitro data suggest that 99m TcN(NOEt) 2 may be a better tracer than 99m Tc-MIBI in tumor imaging and 99m TcN(NOEt) 2 has potential application in clinical use

  5. Magnetic resonance imaging of cervical carcinoma using an endorectal surface coil

    International Nuclear Information System (INIS)

    Brocker, Kerstin A.; Alt, Céline D.; Gebauer, Gerhard; Sohn, Christof; Hallscheidt, Peter

    2014-01-01

    Introduction: The objective of this trial is to investigate the diagnostic value of magnetic resonance imaging (MRI) with an endorectal surface coil for precise local staging of patients with histologically proven cervical cancer by comparing the radiological, clinical, and histological results. Materials and methods: Women with cervical cancer were recruited for this trial between February 2007, and September 2010. All the patients were clinically staged according to the FIGO classification and underwent radiological staging by MRI that employed an endorectal surface coil. The staging results after surgery were compared to histopathology in all the operable patients. Results: A total of 74 consecutive patients were included in the trial. Forty-four (59.5%) patients underwent primary surgery, whereas 30 (40.5%) patients were inoperable according to FIGO and underwent primary radiochemotherapy. The mean age of the patients was 50.6 years. In 11 out of the 44 patients concordant staging results were obtained by all three staging modalities. Thirty-two of the 44 patients were concordantly staged by FIGO and histopathological examination, while only 16 were concordantly staged by eMRI and histopathological examination. eMRI overstaged tumors in 14 cases and understaged them in 7 cases. Conclusions: eMRI is applicable in patients with cervical cancer, yet of no benefit than staging with FIGO or standard pelvic MRI. The most precise preoperative staging procedure still appears to be the clinical examination

  6. On fibrinolytic phenomenon in the cancerous tissue of cervical carcinoma with special reference to irradiation changes

    International Nuclear Information System (INIS)

    Nakamura, Kazuyoshi

    1978-01-01

    In a study undertaken to investigate alterations of fibrinolytic enzymes in cancerous tissue of the cervix under radiotherapy, specimens were taken from malignant tissues of cervical cancer patients during irradiation therapy with Linac x-ray at 1000, 2000 and 3000 rads and were subsequently assayed for fibrinolytic enzyme activities using the fibrin plate method. No plasmin activity was demonstrable in the normal mucosa of the uterine cervix. Cancerous tissue of the uterine cervix also showed no demonstrable plasmin activity. The malignant tissue, as compared to the normal mucosa of the cervix, was found to have a lower activator activity, a higher proactivator activity and lower activities of both antiplasmin inhibitors. During radiotherapy for cervical cancer, plasmin activity was demonstrable in the cancerous tissue and in patients with malignant neoplasm, demonstrating that plasmin activity increased as the radiation dose was increased. A relationship seemed to exist between morphological changes and alterations in the fibrinolytic system of cancerous tissue of the cervix. From these findings it seems that the altered fibrinolytic enzyme system in cancerous tissue may have a close relationship with the growth and development of malignancy and may also have an important role in the occurrence of metastasis. There were some cases, in which an abnormal increase in activator activity occurred during irradiation therapy, leading to the death of the patients. This fact points to the possibility that activator activity might provide a useful index for evaluating the prognosis of cervical cancer. (author)

  7. Dosimetric comparison of vaginal vault ovoid brachytherapy versus intensity-modulated radiation therapy plans in postoperative patients of cervical carcinoma following whole pelvic radiotherapy

    Directory of Open Access Journals (Sweden)

    Divya Khosla

    2014-01-01

    Full Text Available Introduction: Dosimetric study to compare high dose rate (HDR vaginal vault ovoid brachytherapy plan versus intensity-modulated radiation therapy (IMRT boost plan for doses delivered to target volume and organs at risk (OAR in postoperative patients of cervical carcinoma following whole pelvic radiotherapy (WPRT. Materials and Methods: Fifteen postoperative patients of cervical carcinoma suitable for vaginal ovoid brachytherapy following WPRT of 46 Gy/23 fractions/4.5 weeks were included. All were treated with brachytherapy (two sessions of 8.5 Gy each. The equivalent dose for IMRT was calculated by computing biologically effective dose of brachytherapy by linear quadratic model. Dose of brachytherapy (two sessions of 8.5 Gy was equivalent to IMRT dose of 26 Gy/13 fractions. Doses to target volume and OAR were compared between HDR and IMRT plans. Results: Target volume was well covered with both HDR and IMRT plans, but dose with brachytherapy was much higher (P < 0.05. Mean doses, doses to 0.1, 1, 2, and 5cc, 1/3 rd , 1/2, and 2/3 rd volume of bladder and rectum were significantly lower with HDR plans. Conclusion: In postoperative patients of cervical carcinoma, HDR brachytherapy following WPRT appears to be better than IMRT for tumor coverage and reducing dose to critical organs.

  8. Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Kou Y

    2017-09-01

    Full Text Available Yurong Kou,1,* Tengfei Zhao,2,* Shaohui Huang,2 Jie Liu,3 Weiyi Duan,2 Yunjing Wang,2 Zechen Wang,2 Delong Li,2 Chunliu Ning,2 Changfu Sun2 1Department of Oral Biology, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Centre of Science Experiment, China Medical University, Shenyang, Liaoning, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis.Materials and methods: Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3.Results: Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0–7.0. Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0–10.0. Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels.Conclusion: Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated

  9. High-voltage irradiation of xenotransplanted human ovarial, endometrial, and cervical carcinomas

    International Nuclear Information System (INIS)

    Kleine, W.; Wrzodek, W.; Stange, S.; Ladner, H.A.

    1981-01-01

    High-voltage irradiation of four ovarial carcinomas, four endometrial carcinomas and two carcinomas of the cervix is reported on which were transplanted subcutaneously to nu/nu mice. In all cases, the growth was stopped and the tumour receded under irradiation; in 8 cases, after stopping the irradiation with a dose of 30 to 60 Gy the growth went on. Of two carcinomas with decrease in the size and a stopped growth over 20 weeks, in one case no vital cells could be found any more while in the other one there were still numerous vital cells. These showed also after irradiation an unchanged radionucleotid incorporation in the single cell suspension. The effect of a high-voltage irradiation seems to be independent on the histologic picture, but dependent on the dose and the fractioning. The incorporation rates of 3 H-thymidine and 3 H-uridine in the single cell suspension reamined inchanged both before and after irradiation. Irradiation of the xenotransplantate of one side showed the exclusively local effect of this measure. This is confirmed by comparative examinations of the same tumours with a chemotherapy. Thus the nude mouse model offers the possibility of observing the effects of a high-voltage irradiation of human tissue in vivo without involving the total organism of the tumourous animal like in chemotherapy. This shows another field for future questions with nude mice. (orig.) [de

  10. Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, P A; Mandel, U; Therkildsen, M H

    1997-01-01

    differentiated carcinomas, mainly from cervix, expressed the gp230 epitope. The results suggest that a membrane-bound mucin-like molecule, gp230, is associated with the differentiated phenotype of normal mucosal stratified squamous epithelia and that expression of gp230 generally is lost in severe oral...

  11. Histological outcomes in conventional cervical cytology for invasive carcinoma: not always cancer.

    Science.gov (United States)

    Peixoto Pereira, Flávia Regina; Soares, Leila Cristina; de Oliveira, Marco Aurélio Pinho

    2017-11-01

    The value of cytology for the detection of invasive cancer remains unknown. We performed a retrospective cohort study with 884 patients diagnosed of premalignant lesions and invasive carcinoma in cytology. 382 (43.2%) of them had cytological results of high-grade squamous intraepithelial lesions (HSIL), 244 (27.6%) showed low-grade squamous intraepithelial lesions (LSIL), 120 (13.6%) patients had atypical squamous cells of undetermined significance (ASC-US), 67 (7.6%) patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 38 (4.3%) had invasive carcinoma and 33 (3.7%) patients presented with atypical glandular cells (ACG). From 38 patients with cytological results of invasive carcinoma, 24 had confirmatory histological results (63.2%). The other 14 had 4 benign lesions and 10 HSIL. The predictive positive value (PPV) was 63.2%. Cytology results of carcinoma do not confer a definitive diagnosis of invasive lesion, but it is strongly an indication of, at least, a precancerous lesion.

  12. Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis.

    Science.gov (United States)

    Xu, Dianbo; Wang, Danbo; Wang, Shuo; Tian, Ye; Long, Zaiqiu; Ren, Xuemei

    2017-11-01

    The aim of this study was to analyze the relationship between serum squamous cell carcinoma antigen (SCC-Ag) and the clinicopathological features of cervical squamous cell carcinoma. The value of SCC-Ag and computed tomography (CT) for predicting lymph node metastasis (LNM) was evaluated. A total of 197 patients with International Federation of Gynecology and Obstetrics stages IB to IIA cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The SCC-Ag was measured, and CT scans were used for the preoperative assessment of lymph node status. Increased preoperative SCC-Ag levels were associated with International Federation of Gynecology and Obstetrics stage (P = 0.001), tumor diameter of greater than 4 cm (P 4 cm (P = 0.001, OR = 4.019), and greater than one half stromal infiltration (P = 0.002, OR = 3.680) as independent factors affecting SCC-Ag greater than or equal to 2.35 ng/mL. In the analysis of LNM, SCC-Ag greater than or equal to 2.35 ng/mL (P < 0.001, OR = 4.825) was an independent factor for LNM. The area under the receiver operator characteristic curve (AUC) of SCC-Ag was 0.763 for all patients, and 0.805 and 0.530 for IB1 + IIA1 and IB2 + IIA2 patients, respectively; 2.35 ng/mL was the optimum cutoff for predicting LNM. The combination of CT and SCC-Ag showed a sensitivity and specificity of 82.9% and 66% in parallel tests, and 29.8% and 93.3% in serial tests, respectively. The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients with LNM to provide them with the most appropriate therapeutic approach.

  13. Immunohistochemical Expression and Prognostic Significance of CD97 and its Ligand DAF in Human Cervical Squamous Cell Carcinoma.

    Science.gov (United States)

    He, Ying; Wang, Wei; Xu, Lian; Li, Li; Liu, Juan; Feng, Min; Bu, Hong

    2015-09-01

    Accumulating evidences had demonstrated that the CD97, a member of the epidermal growth factor 7-transmembrane family, and its cellular ligand decay accelerating factor (DAF) both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. However, the roles of CD97 and DAF in human cervical squamous cell carcinoma (CSCC) have not been investigated. The purpose of this study was to observe the expression profile of CD97 and DAF in CSCC and evaluate their clinical significance. Immunohistochemistry was used to investigate the expression of CD97 and DAF proteins in 97 patients with CSCC and 53 patients with cervical intraepithelial neoplasia, a precursor lesion of CSCC. CD97 and DAF were absent or only weakly expressed in the normal epithelium of the cervix but were present in 83.5% (81/97) and 90.7% (88/97) of CSCC samples, respectively. Overexpression of CD97 was significantly associated with a high International Federation of Gynecology and Obstetrics stage (P=0.010) and lymph node metastasis (P=0.026). The majority of CSCCs, irrespective of staging/grading classification, displayed strong DAF immunostaining. Kaplan-Meier survival analysis revealed that overexpression of CD97 was associated with a worse prognosis. Multivariate analyses showed that the International Federation of Gynecology and Obstetrics stage (P=0.000), lymph node metastasis (P=0.004), and CD97 expression (P=0.040) were independent risk factors for overall survival. The present study suggested that the expressions of CD97 and DAF were both upregulated in CSCC. The expression level of CD97 in CSCC was associated with the severity of the tumor. Furthermore, CD97 might be an independent poor prognostic factor for CSCC patients.

  14. Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens

    International Nuclear Information System (INIS)

    Mayer, A.; Nemeskeri, C.; Petnehazi, C.; Varga, S.; Naszaly, A.; Borgulya, G.

    2004-01-01

    Background: comprehensive literature on cervical cancer demonstrates, even today, the need for optimization of the timing of external-beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) in the treatment of stage IIA/B-IIIB cervical carcinoma. Patients and methods: 210 patients with carcinoma of the cervix were treated in the Municipal Center of Oncoradiology between January 1991 and December 1996 (FIGO IIA: n = 10, FIGO IIB: n = 113, and FIGO IIIB: n = 87). Two regimens were compared: sequential radiation therapy (SRT) with 4 x 8 Gy HDR-BT to point A followed by EBRT, and continuous radiation therapy (CRT) in which 5 x 6 Gy HDR-BT to point A, one session per week, was integrated into the EBRT. A total dose of 68-70 Gy to point A and 52-54 Gy to point B was given in EBRT with SRT, five fractions per week were applied. Four fractions per week were applied in CRT, i.e., no EBRT was performed on the day of HDR-BT. Total doses to points A and B were identical in both regimens. Overall treatment time (OTT) amounted to 56 days for SRT and 35 days for CRT. Median follow-up time was 3.4 (2.5-4.2) years. Results: progression-free 5-year-survival (PFS) was 71% in the CRT and 56% in the SRT group. Nevertheless, this difference was not statistically significant (p = 1.00), and the same was found in a subgroup analysis of the different tumor stages, showing, however, an unequivocal trend. Late bladder and rectal injuries occurred in 13% and 25%, respectively. Late rectal injuries were significantly more frequent with SRT than CRT (35 patients in the SRT and 18 patients in the CRT group; p = 0.037). This was due to the higher doses per fraction of HDR-BT in the SRT group. No difference was found regarding late bladder injuries (p = 0.837). Conclusion: for the patients included in this study, no advantage has been found so far in using CRT, i.e., shortening the OTT by weekly integration of HDR-BT into EBRT. Nevertheless, an obvious trend exists. The dose of 8 Gy per

  15. Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis

    Directory of Open Access Journals (Sweden)

    Huimin Li

    2017-01-01

    Full Text Available A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted from Arachniodes exilis (TFAE in vivo. Several biochemical assays including hematoxylin-eosin (HE staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted from Arachniodes exilis (TFAE. The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.

  16. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    International Nuclear Information System (INIS)

    Schuhmacher, Jochen; Klivenyi, Gabor; Kaul, Sepp; Henze, Marcus; Matys, Ronald; Hauser, Harald; Clorius, John

    2001-01-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68 Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab') 2 fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10 7 M -1 ) while the binding capacity of cells was high (8.4 x 10 6 BS-MAbs per cell). Tumor uptake of the 67 Ga labeled chelate in pretargeted animals was to 5.8 ± 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125 I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68 Ga and 67 Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68 Ga chelate, clearly visualized all tumors

  17. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    Energy Technology Data Exchange (ETDEWEB)

    Schuhmacher, Jochen; Klivenyi, Gabor; Kaul, Sepp; Henze, Marcus; Matys, Ronald; Hauser, Harald; Clorius, John

    2001-10-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter {sup 68}Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab'){sub 2} fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10{sup 7} M{sup -1}) while the binding capacity of cells was high (8.4 x 10{sup 6} BS-MAbs per cell). Tumor uptake of the {sup 67}Ga labeled chelate in pretargeted animals was to 5.8 {+-} 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with {sup 125}I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the {sup 68}Ga and {sup 67}Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the {sup 68}Ga chelate, clearly visualized all tumors.

  18. Antitumor activity of Portulaca oleracea L. polysaccharides against cervical carcinoma in vitro and in vivo.

    Science.gov (United States)

    Zhao, Rui; Gao, Xu; Cai, Yaping; Shao, Xingyue; Jia, Guiyan; Huang, Yulan; Qin, Xuegong; Wang, Jingwei; Zheng, Xiaoliang

    2013-07-25

    Portulaca oleracea L. has been used as folk medicine in different countries to treat different ailments in humans. P. oleracea L. polysaccharide (POL-P), extracted from P. oleracea L., is found to have bioactivities such as hypoglycemic and hypolipidemic activities, antioxidant and antitumor activities. In our study, a water-soluble polysaccharide (POL-P3b) was successfully purified from Galium verum L. by DEAE cellulose and Sephadex G-200 column chromatography. To evaluate the anticancer efficacy and associated mechanisms of POL-P3b on cervical cancer in vitro and in vivo, we showed that treatment of HeLa cell with POL-P3b inhibited cell proliferation. In addition, POL-P3b significantly inhibited tumor growth in U14-bearing mice. Further analysis indicated that POL-P3b possesses the activity of inhibiting cervical cancer cell growth in vitro and in vivo at a concentration- and time-dependent manner, and the mechanisms were associated with Sub-G1 phase cell cycle arrest, triggering DNA damage and inducing apoptosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice.

    Directory of Open Access Journals (Sweden)

    Neri Mercatelli

    Full Text Available BACKGROUND: MiR-221 and miR-222 are two highly homologous microRNAs whose upregulation has been recently described in several types of human tumors, for some of which their oncogenic role was explained by the discovery of their target p27, a key cell cycle regulator. We previously showed this regulatory relationship in prostate carcinoma cell lines in vitro, underlying the role of miR-221/222 as inducers of proliferation and tumorigenicity. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a number of in vivo approaches confirming our previous data. The ectopic overexpression of miR-221 is able, per se, to confer a high growth advantage to LNCaP-derived tumors in SCID mice. Consistently, the anti-miR-221/222 antagomir treatment of established subcutaneous tumors derived from the highly aggressive PC3 cell line, naturally expressing high levels of miR-221/222, reduces tumor growth by increasing intratumoral p27 amount; this effect is long lasting, as it is detectable as long as 25 days after the treatment. Furthermore, we provide evidence in favour of a clinical relevance of the role of miR-221/222 in prostate carcinoma, by showing their general upregulation in patient-derived primary cell lines, where we find a significant inverse correlation with p27 expression. CONCLUSIONS/SIGNIFICANCE: These findings suggest that modulating miR-221/222 levels may have a therapeutic potential in prostate carcinoma.

  20. A case of entero-cutaneous and vesico-enteral fistula due to radiation for uterine cervical carcinoma

    International Nuclear Information System (INIS)

    Iwakawa, Kazuhide; Kadota, Takeshi; Kobayashi, Nobuaki; Ohnishi, Goro.

    1994-01-01

    Late-phase complications of the intestinal and the urinary tracts due to radiation therapy are very difficult to manage, and ensuing fistulation sometimes necessitates surgrey. We report excellent surgical results for a fistula incuded by radiation therapy in a 61-years-old woman. There were previous histories of receiving combined surgical and radiation (up to 10,000 rad) therapy for a uterine cervical carcinoma at another hospital in 1990, and undergoing several surgical treatments for the consequenct vesico-enteral and vesico-colic fistulas. In January, 1993, the patient was admitted to the department of urology of this hospital because of an abdominal pain, and was transferred to the department under a diagnosis of entero-cutaneous and vesico-enteral fistulas. After local sump suction and skin care, resection of the fistula and involved small intestine conserving the urinary tract was performed, and the omentum was transferred to the resected space. Cholecystectomy was carried out for cholelithiasis. Histological studies revealed atrophy in the mucosal layer and edema in the submucosal layer. Her postoperative course has been satisfactory without any signs of fistulation as of one year after the operation. (author)

  1. Cytotoxic and Apoptotic Effect of Structurally Similar Flavonoids on Parental and Drug-Resistant Cells of a Human Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    Ksenija Durgo

    2009-01-01

    Full Text Available Flavonoids are phytochemicals characterized by a wide range of biological activities, including antioxidant activity, the ability to modulate enzyme or cell receptor activity patterns, and to interfere with essential biochemical pathways. Using HeLa cells of a human cervical carcinoma, and their drug-resistant HeLa CK subline, the effects of three structurally related flavonoids (quercetin, fisetin and luteolin have been examined, in terms of their: (i cytotoxicity, (ii influence on intracellular glutathione (GSH level, (iii influence on glutathione S-transferase (GST activity, and (iv influence on the expression of apoptosis-related genes (PARP, Bcl-2, survivin. Fisetin was more toxic to resistant HeLa CK cell line than to parental cell line, causing decreased expression of survivin in the same cell line. Concentrations of 5 μM of the examined flavonoids caused PARP degradation in parental cell line, leading HeLa cell line into apoptotic cell death. The same event was not determined in the resistant cell line. Fisetin and luteolin induce glutathione and GST in the resistant cell line, pointing to complex cellular effects which could be responsible for higher sensitivity of the resistant cell line in comparison with the parental cell line. Prooxidative nature of the investigated flavonoids was not detected, so free radical formation is not responsible for the induction of GSH, GST and proapoptotic enzymes.

  2. Analysis of prognostic factors in stage IIB-IVA cervical carcinoma treated with radiation therapy: value of computed tomography

    International Nuclear Information System (INIS)

    Ogino, Ichiro; Okamoto, Naoyuki; Andoh, Kazuo; Kitamura, Tatsuo; Okajima, Hiroyuki; Matsubara, Sho

    1997-01-01

    Purpose: To define the influence of the tumor size measured by computed tomography (CT) and lymph node involvement detected by CT in patients treated with radiation therapy for Stage IIB-IVA carcinoma of intact uterine cervix. Methods and Materials: This was a retrospective analysis of 233 patients with uterine cervical cancer managed with both external irradiation and high-dose-rate intracavitary brachytherapy (HDR-ICR) at Kanagawa Cancer Center. The results were analyzed for the end points of absolute survival (AS), disease-free survival (DFS), pelvic control (PC), and central control (CC). The parameters of stage, CT-measured anterior-posterior (AP) cervix size, and CT-detected lymph node metastases were evaluated using univariate and multivariate analysis. Results: The stage, AP cervix size, and lymph node involvement were significant pretreatment factors in univariate analysis with respect to AS, DFS, PC, and CC. Multivariate analysis confirmed that significant risk was associated with certain prognostic parameters. Those in terms of AS, in order of decreasing significance, were lymph node involvement, AP cervix size, age, and total HDR-ICR dose. When DFS was studied, lymph node involvement and AP cervix size were demonstrated to have a significant effect. Stage and lymph node involvement significantly affected PC. Conclusion: Because the International Federation of Gynecological Obstetrics staging system fails to incorporate important prognostic information about tumor volume and lymph node involvement, CT-detected lymph node metastases as well as CT-measured cervix size should be determined as complementary additional prognostic measures

  3. Comparison of CT-based 3D treatment planning with simulator planning of pelvic irradiation of primary cervical carcinoma

    International Nuclear Information System (INIS)

    Knocke, T.H.; Pokrajac, B.; Fellner, C.; Poetter, R.

    1999-01-01

    In a prospective study on 20 subsequent patients with primary cervical carcinoma in Stages I to III simulator planning of a 4-field box-technique was performed. After defining the planning target volume (PTV) in the 3D planning system the field configuration of the simulator planning was transmitted. The resulting plan was compared to a second one based on the defined PTV and evaluated regarding a possible geographical miss and encompassment of the PTV by the treated volume (ICRU). Volumes of open and shaped portals were calculated for both techniques. Planning by simulation resulted in 1 geographical miss and in 10 more cases the encompassment of the PTV by the treated volume was inadequate. For a PTV of mean 1 729 cm 3 the mean volume defined by simulation was 3 120 cm 3 for the open portals and 2 702 cm 3 for the shaped portals. The volume reduction by blocks was 13,4% (mean). With CT-based 3D treatment planning the volume of the open portals was 3,3% (mean) enlarged to 3 224 cm 3 . The resulting mean volume of the shaped portals was 2 458 ccm. The reduction compared to the open portals was 23,8% (mean). The treated volumes were 244 cm 3 or 9% (mean) smaller compared to simulator planning. The 'treated volume/planning target volume ratio' was decreased from 1.59 to 1.42. (orig.) [de

  4. A case of entero-cutaneous and vesico-enteral fistula due to radiation for uterine cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Iwakawa, Kazuhide; Kadota, Takeshi; Kobayashi, Nobuaki [Ehime Univ., Shigenobu (Japan). School of Medicine; Ohnishi, Goro

    1994-11-01

    Late-phase complications of the intestinal and the urinary tracts due to radiation therapy are very difficult to manage, and ensuing fistulation sometimes necessitates surgrey. We report excellent surgical results for a fistula incuded by radiation therapy in a 61-years-old woman. There were previous histories of receiving combined surgical and radiation (up to 10,000 rad) therapy for a uterine cervical carcinoma at another hospital in 1990, and undergoing several surgical treatments for the consequenct vesico-enteral and vesico-colic fistulas. In January, 1993, the patient was admitted to the department of urology of this hospital because of an abdominal pain, and was transferred to the department under a diagnosis of entero-cutaneous and vesico-enteral fistulas. After local sump suction and skin care, resection of the fistula and involved small intestine conserving the urinary tract was performed, and the omentum was transferred to the resected space. Cholecystectomy was carried out for cholelithiasis. Histological studies revealed atrophy in the mucosal layer and edema in the submucosal layer. Her postoperative course has been satisfactory without any signs of fistulation as of one year after the operation. (author).

  5. Evaluation of microvascular densityby CD34 in squamous cell carcinoma of the tongue and its relationship with cervical lymph node metastasis

    Directory of Open Access Journals (Sweden)

    Eshghyar N.

    2009-03-01

    Full Text Available "nBackground and Aim: Angiogenesis plays a central role for development and progression of malignant tumors.It is considered as an important factor for predicting of malignant tumor's behavior such as metastasis to lymph nodes and other clinicopathologic factors. However , it is still a controversial factor especially in oral squamous cell carcinoma.The aim of this study was to evaluate the correlation between angiogenesis and clinicopathologic parameters such as presence of metastatic cervical lymph node in the tongue squamous cell carcinoma. "nMaterials and Methods: In this cross-sectional study, 40 cases of squamous cell carcinoma of the tongue were selected from the archive of cancer institute of Tehran University of Medical Science. Sections were prepared from paraffin blocks and immunohistochemically stained with antibody against CD34. Stained vessels were counted in 4 fields ,the most vascular areas at low magnification, in each areas of intratumoral ,peritumoral and nontumoral adjacent tissue in two groups with metastatic lymphnodes (N+ and without (N-. The average counts from the four most vascular areas were recorded as the mean microvascular density (MVD. Data were analyzed by 3wayANOVA and Independent T- test with p<0.05 as the level of significance. "nResults: High mean MVD-CD34 was significantly correlate with positive cervical lymph node metastasis in intra tumoral and peritumoral areas but there was no significant correlation between mean MVD-CD34 and age, gender, and differentiation of tumor. "nConclusion: Based on the results of this study, CD34 can help us to determine the presence of cervical lymph node metastasis and may also determine the outcome of a primary squamous cell carcinoma of the tongue.

  6. Ploidy, cytokinetics, and histology features of aggressive versus less aggressive uterine cervical squamous cell carcinomas

    International Nuclear Information System (INIS)

    Johnson, T.S.; Peters, L.J.; Adelson, M.; Williamson, K.D.; Sneige, N.; Katz, R.L.; Freedman, R.S.

    1985-01-01

    The authors are investigating the interrelationships of flow cytometric measured ploidy, S-fraction with histology features of uterine cervical squamous cell cancers in an attempt to identify aggressive, high risk tumors and less aggressive tumors. Experimentally, pre-radiotherapy biopsy specimens are being studied using flow ploidy and cell-cycle analysis and microscopic scoring for histology features. The results to date for some 200 patients indicate that there are identifyable aggressive tumors, at high risk for 2 yr local control within each stage of disease and differentiation category (WD, MD, PD). These aggressive tumors usually have high degree DNA abnormalities (triploid or greater), high proliferative activity (%S≥20) compared to the less aggressive tumors characterized by diploid/near diploid DNA content, low to moderate %S (2-19, mean 12). Expression of high S-fraction appears to reflect high growth activity or growth potential and characterizes the aggressive tumors

  7. The Results of Curative Radiation Therapy for 49 Patients of the Uterine Cervical Carcinomas

    International Nuclear Information System (INIS)

    Ryu, Mi Ryeong; Kim, Yeon Sil; Choi, Byung Ock; Yoon, Sei Chul; Shinn, Kyung Sub; Namkoong, Sung Eun; Kim, Seung Jo

    1992-01-01

    Fifty patients with carcinoma of the uterine cervix received curative radiotherapy by external irradiation of the whole pelvis and intracavitary radiation at the Department of Therapeutic Radiology, Kangnam St. Mary Hospital from September,1983 to October, 1986. External beam whole pelvic irradiation was done first up to 4500-5940 cGy in 5 weeks to 6.5 weeks, followed by an intracavitary radiation. Total dose of radiation to point A varied from 6500 cGy to l1344 cGy (average 6764 cGy). Of the 50 patients, one patient was lost to follow up and follow up period of the remaining 49 patients ranged from 3 months to 93 months (median 32 months). According to FIGO classification, 6 (12.2%) were in stage I b, 6(12.2%) in stage I a, 25(51%) in stage II b, 7(14%) in stage III, and 5(10.2%) in stage IV. Age of the patients ranged from 33 to 76 years (Median 60 years). Pathologically, forty six(94%) patients had squamous cell carcinoma, 2 (4% had adenocarcinoma, and 1 (2%) had adenosquamous cell carcinoma. Overall response rate was 84%. 5-year survival rate was 49% for entire group (75% for stage I b, 83% for stage II a, 42.5% for stage II b, 25% for stage III, 40% for stage IV). Complications were observed in 11(22.4%) patients, who revealed rectal complications with most common frequency. Others were self limiting trifle ones such as wet desquamation, fatigue, mild leukopenia, etc. The correlation of the survival rate with various factors (age, dose, Hb level, pelvic lymph node status, performance status, local recurrence) was evaluated but showed no statistical significance except the age and local recurrence in this series; survival of patients less than 50 years of age was worse than that of the older, and the presence of local recurrence had worse prognosis(p< 0.05)

  8. Novel Tc-99m labeled ELR-containing 6-mer peptides for tumor imaging in epidermoid carcinoma xenografts model. A pilot study

    International Nuclear Information System (INIS)

    Kim, Dae-Weung; Kim, Woo-Hyoung; Kim, Myoung-Hyoun; Kim, Chang-Guhn

    2013-01-01

    ELR-containing peptides targeting CXCR2 could be the excellent candidate for targeting ligand of molecular tumor imaging. In this study, we had developed two ELR-containing 6-mer peptides and evaluated the diagnostic performance of Tc-99m labeled 6-mer peptides as a molecular imaging agent in murine models bearing KB epidermoid carcinoma. Peptides were synthesized using Fmoc solid phase peptide synthesis. Radiolabeling efficiency with Tc-99m was evaluated using instant thin-layer chromatography. In KB epidermoid cancer-bearing mice, gamma images had acquired and tumor-to-muscle uptake ratio was calculated. Competition and biodistribution studies had performed. Two 6-mer peptides, ELR-ECG and ECG-ELR were successfully synthesized. After radiolabeling procedures with Tc-99m, the complex Tc-99m ELR-ECG and Tc-99m ECG-ELR were prepared in high yield. In the gamma camera imaging of murine model, Tc-99m ELR-ECG was substantially accumulated in the subcutaneously engrafted tumor and tumor uptake had been suppressed by the free ELR co-injection. However, Tc-99m ECG-ELR was minimally accumulated in the tumor. Two ELR-containing 6-mer peptides, ELR-ECG and ECG-ELR, were developed as a molecular imaging agent to target CXCR2 of epidermoid carcinoma. Tc-99m ELR-ECG had showed significant uptake in tumor and it was good candidate for a tumor imaging. (author)

  9. Effect of cisplatin on the clinically relevant radiosensitivity of human cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Britten, Richard A.; Evans, Andrew J.; Allalunis-Turner, M. Joan; Pearcey, Robert G.

    1996-01-01

    Purpose: To evaluate the effect of clinically relevant levels of cisplatin on the radiosensitivity of human cervical tumor cells, and to estimate what changes in local control rates might be expected to accrue from the concomitant use of cisplatin during fractionated radiotherapy. Methods and Materials: The effects of concomitant cisplatin (1 μg/ml, a typical intratumor concentration) on the clinically relevant radiosensitivity, i.e., surviving fraction after 2 G (SF 2 ) values, was determined in 19 cloned human cervical tumor cell lines. These early passage cell lines had SF 2 values ranging from 0.26 to 0.87. Results: The concomitant administration of cisplatin reduced the clinically relevant radiosensitivity in the majority (11 out of 19) of the human tumor cell lines investigated. In only 4 out of 19 was any radiosensitization observed, and in 4 out of 19 cell lines there was no significant change in radiosensitivity. However, the sum of the independent cell killing by radiation and cisplatin, was approximately twofold higher than after radiation alone. There was no apparent dependence of the cisplatin-induced changes in SF 2 values upon the level of cell killing by cisplatin. However, there is a suggestion that concomitant cisplatin administration may have a differential effect in inherently radiosensitive and resistant human tumor cell lines. Conclusions: Our data suggest that concomitant cisplatin/radiotherapy regimens may result in a higher level of local tumor control, but primarily through additive toxicity and not through radiosensitization. Future improvements in local tumor control may, thus, be derived by increasing the total dose of cisplatin

  10. EVALUATION OF P16INK4A PROTEIN AS A BIOMARKER FOR CERVICAL INTRAEPITHELIAL NEOPLASIA AND SQUAMOUS CELL CARCINOMA OF THE UTERINE CERVIX

    Directory of Open Access Journals (Sweden)

    Biljana Đorđević

    2011-06-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well known. Interaction of HPV proteins with cellular regulatory proteins leads to up regulation of p16INK4A. The aim of this study was to evaluate p16INK4A protein as a biomarker for CIN lesions and squamous cell carcinoma on biopsy specimens of patients who underwent biopsy of the uterine cervix due to abnormal cytological finding.The authors analyzed biopsies from 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix. Expression of p16INK4A in CIN and invasive squamous cell carcinoma was immunohistochemically analyzed by using monoclonal anti-p16INK4A antibody.A total of 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix (mean age 40.2±11.5 years, range 20-74 years were analyzed. CIN I lesions were found in 27 (54%, CIN II/CIN III lesions in 9 (18%, and invasive squamous cell carcinoma in 14 (28% patients. Differences in the expression of p16INK4A between CIN I, CIN II/CIN III and squamous cell carcinoma were statistically significant (p<0.0001. Expression of p16INK4A showed low sensitivity (7%, specificity (8%, positive predictive value (8%, and negative predictive value (7% for CIN I. Sensitivity, specificity, positive predictive value, and negative predictive value of p16INK4A were 78%, 61%, 30%, and 93% for CIN II/CIN III, and 100%, 75%, 61%, and 100% for squamous cell carcinoma, respectively.Results of this study suggest that p16INK4A protein may be a sensitive biomarker for CIN II/CIN III lesions and invasive squamous cell carcinoma of the uterine cervix.

  11. Branchial cleft cyst: An unusual site for the cervical metastasis of nasopharyngeal carcinoma.

    Science.gov (United States)

    Liao, Yu-Chang; Adel, Mohamad; Lee, Li-Yu; Chang, Kai-Ping

    2018-04-01

    Cancers found in the resected branchial cleft cyst are rare clinically but usually impose substantive diagnostic and treatment challenges for clinicians. A 31-year-old man presented with a lateral neck mass that was suspected to be an inflammatory branchial cleft cyst. After excision, the pathologic specimen revealed a benign cystic appearance with a focus of undifferentiated carcinoma. Serologic tests for Epstein-Barr virus were negative. A positron emission tomography scan and upper aerodigestive tract endoscopies were negative for any other suspicious lesion. The patient underwent random biopsies of the nasopharynx, tongue base, and hypopharynx and bil tonsillectomy. Pathologic examination of the nasopharyngeal biopsies showed the presence of undifferentiated carcinoma. The cancerous part of the branchial cleft cyst and this nasopharyngeal specimen were positive for the latent membrane protein-1 and EBV-encoded RNAs of Epstein-Barr virus (EBV) and confirmed our diagnosis. This is the first report of a NPC metastasizing to a branchial cleft cyst. Molecular diagnostic techniques facilitate the definite diagnosis that enabled us to refine treatment plans and offered the patient a favorable outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Clinical efficacy of FDG-PET scan in the patients with primary or recurrent gynecologic malignancies: clinical experiences with FDG-PET scan in cervical carcinoma of uterus

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Hoon

    1998-12-01

    This study was done to evaluate the clinical feasibility of FDG-PET scan in patients with cervical carcinoma. PET-scans were performed in 74 patients with cervical carcinoma from March, 1998 to September, 1998. Fourteen cases were done at pretreatment period and sixty cases were done at post-treatment follow up period. In this study, the scans were obtained after bladder emptying by foley catheter insertion and diuretics to reduce the tracer activity in the bladder and improve the images of central lesions. We could find some incidental recurrent or metastatic lesions by FDG-PET scan (at pretreatment; 5 cases, at post-treatment; clinically no evidence of disease; 8 cases). FDG-PET scan had high sensitivity (100%) for central lesions and metastatic lymph nodes of cervical cancer but could not precisely define the anatomic location of the cancer and the sensitivity was not superior than MRI. Earlier detection of metastatic lymph nodes was superior than CT/MRI (sensitivity; 100 %) for metastatic lymph nodes. Also we found 3 double primary cancers incidentally (2 lung cancers and 1 thyroid cancer). In conclusion, FDG-FET scan might be useful for the earlier of hidden lesions that cannot be detected by routine conventional methods and differential diagnosis with radiation fibrosis and benign lymph adenophy.

  13. Labelling of anti-human bladder tumor chimeric antibody with 99Tcm and radioimmunoimaging of bladder carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Zhang Chunli; Wang Rongfu; Fu Zhanli; Bai Yin; Ding Yi; Yu Lizhang

    2003-01-01

    Objective: To study the in vitro immunoreactivity and in vivo tissue distribution, tumor targeting property of anti-human bladder tumor human-murine chimeric antibody (ch-BDI) labeled with 99 Tc m and to investigate its possibility for being used in guiding diagnosis and guiding therapy of bladder cancer. Methods: The ch-BDI was labeled with 99 Tc m by improved Schwarz method and the labeled antibody was purified by Sephadex G-50. Labeling yield and radiochemical purity were measured by paper chromatography. The immunoreactive fraction and association constant (K a ) were measured by Lindmo method and Scatchard analysis, respectively. 11.1 MBq (30 μg) 99 Tc m -ch-BDI was intravenously injected into nude mice bearing human bladder cancer xenografts in the right thigh and radioimmunoimaging (RII) was performed 2, 6, 20 and 24 h postinjection. The images were processed by region of interest (ROI) method to acquire the counts of whole body and the tumor and the counts ratios of tumor to contralateral normal tissue or to tissues of other non-tumor bearing organs. The mice were killed after 24 h postinjection imaging and tissue distribution was measured. %ID/g and target to nontarget (T/NT) ratios were calculated. Results: The labeling yield and radiochemical purity of 99 Tc m -ch-BDI were (66.5±7.3)% and >90%, respectively. The immunoreactive fraction was 76% and K a was 3.56 x 10 9 L/mol. RII showed that the tumor was clearly visualized 6 h postinjection and becoming clearer along with time prolonging. The radioactivity of whole body decreased rapidly with time, whereas the radioactivity of the tumor decreased slowly. The T/NT ratios was increased with time. Biodistribution results showed that tumor uptake was 17.4%ID/g 24 h postinjection. T/NT ratios were very high except for the kidney. T/NT ratios for brain, muscle, intestinal wall, bone and heart wall were 136.0, 55.1, 39.3, 29.7 and 27.9, respectively. Conclusion: 99 Tc m -ch-BDI exhibits excellent

  14. Intensity Modulated Proton Beam Radiation for Brachytherapy in Patients With Cervical Carcinoma

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    Clivio, Alessandro [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Kluge, Anne [Department of Radiation Oncology, Charité University Hospital, Berlin (Germany); Cozzi, Luca, E-mail: lucozzi@iosi.ch [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Köhler, Christhardt [Department of Gynecology, Charité University Hospital, Berlin (Germany); Neumann, Oliver [Department of Radiation Oncology, Charité University Hospital, Berlin (Germany); Vanetti, Eugenio [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Wlodarczyk, Waldemar; Marnitz, Simone [Department of Radiation Oncology, Charité University Hospital, Berlin (Germany)

    2013-12-01

    Purpose: To evaluate intensity modulated proton therapy (IMPT) in patients with cervical cancer in terms of coverage, conformity, and dose–volume histogram (DVH) parameters correlated with recommendations from magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Eleven patients with histologically proven cervical cancer underwent primary chemoradiation for the pelvic lymph nodes, the uterus, the cervix, and the parametric region, with a symmetric margin of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a simultaneous boost. For several reasons, the patients were unable to undergo brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to the cervix, including the macroscopic tumor with an MRI-guided target definition, with an isotropic margin of 5 mm for planning target volume (PTV) definition. Groupe-Europeen de Curietherapie and European society for Radiotherapy and Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the RapidArc (RA). Results: The dose to the high-risk volume was calculated with α/β = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean dose of 38.2 ± 5.0 Gy (35.0 ±1.8 Gy for RA). The D{sub 98%} was 31.9 ± 2.6 Gy (RA: 30.8 ± 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose (EQD2) (α/β = 3) to 2 cm{sup 3} of the rectal wall, sigmoid wall, and bladder wall was 62.2 ± 6.4 Gy, 57.8 ± 6.1 Gy, and 80.6 ± 8.7 Gy (for RA: 75.3 ± 6.1 Gy, 66.9 ± 6.9 Gy, and 89.0 ± 7.2 Gy, respectively). For the IMPT boost plans in combination with external beam radiation therapy, all DVH parameters correlated with <5% risk for grades 2 to 4 late gastrointestinal and genitourinary toxicity. Conclusion: In patients who are not eligible for brachytherapy, IMPT as a boost

  15. Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs)

    International Nuclear Information System (INIS)

    Bordón, Elisa; Henríquez Hernández, Luis Alberto; Lara, Pedro C; Pinar, Beatriz; Fontes, Fausto; Rodríguez Gallego, Carlos; Lloret, Marta

    2009-01-01

    Cervical cancer is treated mainly by surgery and radiotherapy. Toxicity due to radiation is a limiting factor for treatment success. Determination of lymphocyte radiosensitivity by radio-induced apoptosis arises as a possible method for predictive test development. The aim of this study was to analyze radio-induced apoptosis of peripheral blood lymphocytes. Ninety four consecutive patients suffering from cervical carcinoma, diagnosed and treated in our institution, and four healthy controls were included in the study. Toxicity was evaluated using the Lent-Soma scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24, 48 and 72 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide to determine early and late apoptosis. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis (RIA) increased with radiation dose and time of incubation. Data strongly fitted to a semi logarithmic model as follows: RIA = βln(Gy) + α. This mathematical model was defined by two constants: α, is the origin of the curve in the Y axis and determines the percentage of spontaneous cell death and β, is the slope of the curve and determines the percentage of cell death induced at a determined radiation dose (β = ΔRIA/Δln(Gy)). Higher β values (increased rate of RIA at given radiation doses) were observed in patients with low sexual toxicity (Exp(B) = 0.83, C.I. 95% (0.73-0.95), p = 0.007; Exp(B) = 0.88, C.I. 95% (0.82-0.94), p = 0.001; Exp(B) = 0.93, C.I. 95% (0.88-0.99), p = 0.026 for 24, 48 and 72 hours respectively). This relation was also found with rectal (Exp(B) = 0.89, C.I. 95% (0.81-0.98), p = 0.026; Exp(B) = 0.95, C.I. 95% (0.91-0.98), p = 0.013 for 48 and 72 hours respectively) and urinary (Exp(B) = 0.83, C.I. 95% (0.71-0.97), p = 0.021 for 24 hours) toxicity. Radiation induced apoptosis at different time points and radiation doses fitted to a semi logarithmic model defined

  16. Cervical lymph node metastasis of oral squamous cell carcinomas. CT enhancement and histopathological evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Etoh, Yohei; Kimura, Takuji; Sasaki, Akira; Kishimoto, Koji; Matsumura, Tomohiro; Kishi, Kanji [Okayama Univ. (Japan). Dental School

    2000-06-01

    A comparison of the results of histopathological and enhanced CT examinations were carried out for 88 patients with oral squamous cell carcinomas who underwent neck dissection. CT scanning (5-mm thick section) images obtained during bolus/drip injection of Iopamidol were routinely taken through the neck. Ninety-two of 1634 nodes were histologically diagnosed as metastatic. Low density areas surrounding enhancement rims were metastatic nodal central necrosis or keratinization. Enhanced areas in many metastatic nodes were considered to be lymphatic architecture, not metastatic masses especially in the avascular keratinization. Enhanced CT produced accurate information of lymph node size, location, shape, grouping and spread from nodes to adjacent structures. However, it was considered that not every metastatic lymph node should show enlargement and/or enhancement. Improved assessment of solid metastatic features of lymph nodes (shape, size, and involvement) may be achieved with the aid of thin-thickness CT. (author)

  17. Cervical lymph node metastasis of oral squamous cell carcinomas. CT enhancement and histopathological evaluations

    International Nuclear Information System (INIS)

    Etoh, Yohei; Kimura, Takuji; Sasaki, Akira; Kishimoto, Koji; Matsumura, Tomohiro; Kishi, Kanji

    2000-01-01

    A comparison of the results of histopathological and enhanced CT examinations were carried out for 88 patients with oral squamous cell carcinomas who underwent neck dissection. CT scanning (5-mm thick section) images obtained during bolus/drip injection of Iopamidol were routinely taken through the neck. Ninety-two of 1634 nodes were histologically diagnosed as metastatic. Low density areas surrounding enhancement rims were metastatic nodal central necrosis or keratinization. Enhanced areas in many metastatic nodes were considered to be lymphatic architecture, not metastatic masses especially in the avascular keratinization. Enhanced CT produced accurate information of lymph node size, location, shape, grouping and spread from nodes to adjacent structures. However, it was considered that not every metastatic lymph node should show enlargement and/or enhancement. Improved assessment of solid metastatic features of lymph nodes (shape, size, and involvement) may be achieved with the aid of thin-thickness CT. (author)

  18. HPV16-E2 induces prophase arrest and activates the cellular DNA damage response in vitro and in precursor lesions of cervical carcinoma.

    Science.gov (United States)

    Xue, Yuezhen; Toh, Shen Yon; He, Pingping; Lim, Thimothy; Lim, Diana; Pang, Chai Ling; Abastado, Jean-Pierre; Thierry, Françoise

    2015-10-27

    Cervical intraepithelial neoplasia (CIN) is caused by human papillomavirus (HPV) infection and is the precursor to cervical carcinoma. The completion of the HPV productive life cycle depends on the expression of viral proteins which further determines the severity of the cervical neoplasia. Initiation of the viral productive replication requires expression of the E2 viral protein that cooperates with the E1 viral DNA helicase. A decrease in the viral DNA replication ability and increase in the severity of cervical neoplasia is accompanied by simultaneous elevated expression of E6 and E7 oncoproteins. Here we reveal a novel and important role for the HPV16-E2 protein in controlling host cell cycle during malignant transformation. We showed that cells expressing HPV16-E2 in vitro are arrested in prophase alongside activation of a sustained DDR signal. We uncovered evidence that HPV16-E2 protein is present in vivo in cells that express both mitotic and DDR signals specifically in CIN3 lesions, immediate precursors of cancer, suggesting that E2 may be one of the drivers of genomic instability and carcinogenesis in vivo.

  19. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status.

    Science.gov (United States)

    Amsbaugh, Mark J; Yusuf, Mehran; Cash, Elizabeth; Silverman, Craig; Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin; Perez, Cesar; Bert, Robert; Redman, Rebecca; Dunlap, Neal

    2016-10-01

    To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ(2), Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. The rates of HPV/p16 positivity (Phigh-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Small bowel perforation without tumor recurrence after radiotherapy for cervical carcinoma: report of seven cases.

    Science.gov (United States)

    Yamashita, Hideomi; Nakagawa, Keiichi; Tago, Masao; Igaki, Hiroshi; Shiraishi, Kenshirou; Nakamura, Naoki; Sasano, Nakashi; Yamakawa, Sen; Ohtomo, Kuni

    2006-04-01

    We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer. A database consisting of 95 Japanese women with stage 0-4 A cervix cancer treated between 1991 and 2004 contained seven patients (7.4%) with small bowel perforation. The median age at the time of perforation was 72.5 years (range 62-78). The median time from completion of radiotherapy to perforation was 6 months (range 2-58). Surgery (one small bowel resection and anastomosis with diversion; six small bowel resection and anastomosis) was performed immediately in all seven patients. One of seven patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel adhesion was detected during the operation in only three cases (43%). Signs of peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all seven patients. The perforation site was ileum in all seven cases. In all patients, pathological changes were compatible with postirradiation injury of the gastrointestinal tract. The presenting complaints of patients with bowel perforation following radiotherapy vary, and signs of peritonitis may be absent. Emergency physicians must be alert for these complications in patients who have been treated with radiotherapy.

  1. Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.

    Science.gov (United States)

    Chen, Ming-Feng; Yang, Chih-Min; Su, Cheng-Ming; Liao, Jiunn-Wang; Hu, Miao-Lin

    2011-01-01

    Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

  2. Dosimetric comparison between step-shoot intensity-modulated radiotherapy and volumetric-modulated arc therapy for upper thoracic and cervical esophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Min; Li, Qilin; Ning, Zhonghua; Gu, Wendong; Huang, Jin; Mu, Jinming; Pei, Honglei, E-mail: hongleipei@126.com

    2016-07-01

    To compare and analyze the dosimetric characteristics of volumetric modulated arc therapy (VMAT) vs step-shoot intensity-modulated radiation therapy (sIMRT) for upper thoracic and cervical esophageal carcinoma. Single-arc VMAT (VMAT1), dual-arc VMAT (VMAT2), and 7-field sIMRT plans were designed for 30 patients with upper thoracic or cervical esophageal carcinoma. Planning target volume (PTV) was prescribed to 50.4 Gy in 28 fractions, and PTV1 was prescribed to 60 Gy in 28 fractions. The parameters evaluated included dose homogeneity and conformality, dose to organs at risk (OARs), and delivery efficiency. (1) In comparison to sIMRT, VMAT provided a systematic improvement in PTV1 coverage. The homogeneity index of VMAT1 was better than that of VMAT2. There were no significant differences among sIMRT, VMAT1, and VMAT2 in PTV coverage. (2) VMAT1 and VMAT2 reduced the maximum dose of spinal cord as compared with sIMRT (p < 0.05). The rest dose-volume characteristics of OARs were similar. (3) Monitor units of VMAT2 and VMAT1 were more than sIMRT. However, the treatment time of VMAT1, VMAT2, and sIMRT was (2.0 ± 0.2), (2.8 ± 0.3), and (9.8 ± 0.8) minutes, respectively. VMAT1 was the fastest, and the difference was statistically significant. In the treatment of upper thoracic and cervical esophageal carcinoma by the AXESSE linac, compared with 7-field sIMRT, VMAT showed better PTV1 coverage and superior spinal cord sparing. Single-arc VMAT had similar target volume coverage and the sparing of OAR to dual-arc VMAT, with shortest treatment time and highest treatment efficiency in the 3 kinds of plans.

  3. Radiotherapy versus concurrent 5-day cisplatin and radiotherapy in locally advanced cervical carcinoma. Long-term results of a Phase III randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Viorica; Coza, Ovidiu; Ghilezan, Nicolae [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Radiation Oncology; ' Iuliu Hatieganu' Univ. of Medicine and Pharmacy, Cluj-Napoca (Romania); Ordeanu, Claudia; Todor, Nicolae [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Radiation Oncology; Traila, Alexandru [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Surgery; Rancea, Alin [' Iuliu Hatieganu' Univ. of Medicine and Pharmacy, Cluj-Napoca (Romania); ' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Surgery

    2009-03-15

    Purpose: To prove the superiority of concurrent radiochemotherapy (RTCT) over radiotherapy (RT) alone in locally advanced cervical carcinoma. Patients and Methods: In this randomized monocentric phase III study, 566 patients with squamous cell carcinoma of the cervix were included: 284 in arm A (RT) and 282 in arm B (concurrent RTCT with cisplatin 20 mg/m{sup 2} x 5 days). 238 patients (42%) were in stage IIB, 209 (37%) in stage IIIA, and 119 (21%) in stage IIIB. The median follow-up was 62.8 months. RT to the pelvis was delivered to a dose of 46 Gy/23 fractions. A cervical boost was given using the X-ray arch technique or high-dose-rate intracavitary brachytherapy at a dose of 10 Gy. Thereafter, patients were evaluated: those with good response optionally underwent surgery and the others continued RT until 64 Gy/pelvis (with or without CT according to randomization) and 14 Gy/central tumor volume. Results: The 5-year survival rate was statistically significantly superior in the concurrent RTCT group (74%) versus the RT group (64%; p < 0.05). In patients undergoing surgery after RT or RTCT, superior results were obtained, compared to the nonoperated patients: 5-year survival rate 86% versus 53% (p < 0.01). 192 failures were recorded: 109 (38%) after RT alone versus 83 (29%) after concurrent RTCT (p < 0.01). Conclusion: The results of this study prove the obvious superiority of concurrent RTCT with 5-day cisplatin compared to RT alone in patients with locally advanced cervical carcinoma, regarding local control (78% vs. 67%) and 5-year survival rates (74% vs. 64%). (orig.)

  4. Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Ordonez, R.; Federico, M. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Valenciano, A. [Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Bordon, E. [Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Rodriguez-Gallego, C. [Hospital Universitario de Gran Canaria Dr. Negrin, Immunology Department, Las Palmas de Gran Canaria (Spain)

    2014-02-15

    A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

  5. Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

    International Nuclear Information System (INIS)

    Ordonez, R.; Federico, M.; Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C.; Valenciano, A.; Bordon, E.; Rodriguez-Gallego, C.

    2014-01-01

    A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

  6. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  7. [miR-497 suppresses proliferation of human cervical carcinoma HeLa cells by targeting cyclin E1].

    Science.gov (United States)

    Han, Jiming; Huo, Manpeng; Mu, Mingtao; Liu, Junjun; Zhang, Jing

    2014-06-01

    To evaluate the effect of miR-497 on proliferation of human cervical carcinoma HeLa cells and target relationship between miR-497 and cyclin E1 (CCNE1). Pre-miR-497 sequences were synthesized and cloned into pcDNATM6.2-GW to construct recombinant plasmid pcDNATM6.2-GW-pre-miR-497 and identified by real-time quantitative PCR (qRT-PCR). In addition, sequences of the wild-type CCNE1 (WT-CCNE1) and mutant CCNE1 (MT-CCNE1) were respectively cloned into pmirGLO vectors. MTT assay was used to explore the impact of miR-497 on the proliferation of HeLa cells. Furthermore, the target effect of miR-497 on the CCNE1 was identified by dual-luciferase reporter assay system, qRT-PCR and Western blotting. The recombinant plasmids pcDNATM6.2-GW-pre-miR-497 and pmirGLO-WT-CCNE1, pmirGLO-MT-CCNE1 were successfully constructed, and the miR-497 expression level in HeLa cells transfected with pre-miR-497 was significantly higher than that in the neg-miR group (PHeLa cells (PHeLa cells with pre-miR-497 transfection (PHeLa cells transfected with pre-miR-497 (PHeLa cells could suppress cell proliferation by targeting CCNE1.

  8. [miR-25 promotes cell proliferation by targeting RECK in human cervical carcinoma HeLa cells].

    Science.gov (United States)

    Qiu, Gang; Fang, Baoshuan; Xin, Guohong; Wei, Qiang; Yuan, Xiaoye; Wu, Dayong

    2015-01-01

    To investigate the effect of miR-25 on the proliferation of human cervical carcinoma HeLa cells and its association with reversion-inducing cysteine-rich protein with Kazal motifs (RECK). The recombinant plasmids of pcDNATM6.2-GW-pre-miR-25, pmirGLO-RECK-WT, pmirGLO-RECK-MT and anti-miR-25 were constructed, and their transfection efficiencies into HeLa cells were identified by real-time quantitative PCR (qRT-PCR). The potential proliferation-stimulating function of miR-25 was analyzed by MTT assay in HeLa cells. Furthermore, the target effect of miR-25 on the RECK was determined by dual-luciferase reporter assay system, qRT-PCR and Western blotting. Sequence analysis demonstrated that the recombinant plasmids of pcDNATM6.2-GW-pre-miR-25 and pmirGLO-RECK-WT, pmirGLO-RECK-MT were successfully constructed, and qRT-PCR revealed that the transfection efficiencies of pre-miR-25 and anti-miR-25 were desirable in HeLa cells. MTT assay showed that miR-25 over-expression promoted the proliferation of HeLa cells. In addition, the luciferase activity was significantly reduced in HeLa cells cotransfected with pre-miR-25 and RECK-WT. The qRT-PCR and Western blotting indicated that the expression level of RECK was up-regulated in HeLa cells transfected with anti-miR-25 at the transcriptional and posttranscriptional levels. miR-25 could promote cell proliferation by targeting RECK in HeLa cells.

  9. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck mucosal site treated with radiation therapy with palliative intent

    International Nuclear Information System (INIS)

    Erkal, Haldun S.; Mendenhall, William M.; Amdur, Robert J.; Villaret, Douglas B.; Stringer, Scott P.

    2001-01-01

    Minimal information has been published about the results of palliative irradiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Forty patients with this diagnosis were treated at the University of Florida with radiation therapy with palliative intent. The nodal response rate was 65% and the symptomatic response rate was 57% at 1 year. The absolute survival rate was 25% at 1 year, as was the cause-specific survival rate. Radiotherapy successfully palliates more than half of those treated. Approximately one fourth are alive 1 year after irradiation

  10. Expressions of EphA2 and EphrinA-1 in early squamous cell cervical carcinomas and their relation to prognosis

    OpenAIRE

    Holm, Ruth; de Putte, Gregg Van; Suo, Zhenhe; Lie, A Kathrine; Kristensen, Gunnar B

    2008-01-01

    By using immunohistochemistry we investigated the expression of EphA2 and EphrinA-1 in 217 early squamous cell cervical carcinomas and examine their prognostic relevance. For EphA2 expression, 21 tumors (10%) showed negative, 108 (50%) weak positive, 69 (32%) moderate positive and 19 (9%) strong positive, whereas for EphrinA-1 expression, 33 tumors (15%) showed negative, 91 (42%) weak positive, 67 (31%) moderate positive and 26 (12%) strong positive. In univariate analysis high expression (st...

  11. Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation

    International Nuclear Information System (INIS)

    Reddy, Sarada P.; Marks, James E.

    1997-01-01

    Purpose: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. Methods and Materials: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. Results: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. Conclusion: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective

  12. Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma

    International Nuclear Information System (INIS)

    Levine, E.L.; Renehan, A.; Gossiel, R.; Davidson, S.E.; Roberts, S.A.; Chadwick, C.; Wilks, D.P.; Potten, C.S.; Hendry, J.H.; Hunter, R.D.; West, C.M.L.

    1995-01-01

    Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the percentage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were also recorded as markers for proliferation. Patients were divided into those with an AI above or below the median and in general increasing apoptosis was associated with poor prognosis. The 5-year survival rate for tumours with an AI below the median was 79% and was significantly greater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurrence-free rate for patients with an AI below the median compared with those with an AI above the median (79 versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic indicators. Patients with both an SF2 and AI value above the median did badly (25% 5-year survival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showed correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apoptosis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients. The study raises the possibility of AI and SF2 being used together as predictors of tumour response to radiotherapy

  13. Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.

    Science.gov (United States)

    Correnti, Maria; Medina, Francisco; Cavazza, María Eugenia; Rennola, Antonieta; Avila, Maira; Fernándes, Andreína

    2011-06-01

    Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women. Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections. HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31. Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status

    International Nuclear Information System (INIS)

    Amsbaugh, Mark J.; Yusuf, Mehran; Cash, Elizabeth; Silverman, Craig; Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin; Perez, Cesar; Bert, Robert; Redman, Rebecca; Dunlap, Neal

    2016-01-01

    Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ"2, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain

  15. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status

    Energy Technology Data Exchange (ETDEWEB)

    Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States); Yusuf, Mehran [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States); Cash, Elizabeth [Department of Otolaryngology, University of Louisville, Louisville, Kentucky (United States); Silverman, Craig [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States); Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin [Department of Otolaryngology, University of Louisville, Louisville, Kentucky (United States); Perez, Cesar [Division of Medical Oncology, Department of Medicine, University of Louisville, Louisville, Kentucky (United States); Bert, Robert [Department of Diagnostic Radiology, University of Louisville, Louisville, Kentucky (United States); Redman, Rebecca [Division of Medical Oncology, Department of Medicine, University of Louisville, Louisville, Kentucky (United States); Dunlap, Neal [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States)

    2016-10-01

    Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ{sup 2}, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain

  16. BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy.

    Science.gov (United States)

    Henríquez-Hernández, Luis Alberto; Lloret, Marta; Pinar, Beatriz; Bordón, Elisa; Rey, Agustín; Lubrano, Amina; Lara, Pedro Carlos

    2011-09-01

    To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect. Fifty consecutive patients, who achieved complete response to treatment, from a whole series of 60 cases suffering from non-metastatic localized cervical carcinoma, were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in January 2011. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) with concomitant cisplatin at 40 mg/m2/week doses followed by brachytherapy. Oncoprotein expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. No relation was found between BCL-2 and clinicopathological variables. High MVP/IGF-1R/BCL-2 tumour expression was strongly related to poor local and regional disease-free survival (PMVP, and IGF-1R overexpression were related to poorer clinical outcome in cervical cancer patients who achieved clinical complete response to radiochemotherapy. The NHEJ repair protein Ku70/80 expression could be involved in the regulation of these oncoproteins. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The Proteasome Inhibitor MG-132 Protects Hypoxic SiHa Cervical Carcinoma Cells after Cyclic Hypoxia/Reoxygenation from Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Frank Pajonk

    2006-12-01

    Full Text Available INTRODUCTION: Transient hypoxia and subsequent reoxygenation are common phenomena in solid tumors that greatly influence the outcome of radiation therapy. This study was designed to determine how varying cycles of hypoxia/reoxygenation affect the response of cervical carcinoma cells irradiated under oxic and hypoxic conditions and whether this could be modulated by proteasome inhibition. MATERIALS AND METHODS: Plateau-phase SiHa cervical carcinoma cells in culture were exposed to varying numbers of 30-minute cycles of hypoxia/reoxygenation directly before irradiation under oxic or hypoxic conditions. 26S Proteasome activity was blocked by addition of MG-132. Clonogenic survival was measured by a colonyforming assay. RESULTS: Under oxic conditions, repeated cycles of hypoxia/reoxygenation decreased the clonogenic survival of SiHa cells. This effect was even more pronounced after the inhibition of 26S proteasome complex. In contrast, under hypoxic conditions, SiHa cells were radioresistant, as expected, but this was increased by proteasome inhibition. CONCLUSIONS: Proteasome inhibition radiosensitizes oxygenated tumor cells but may also protect tumor cells from ionizing radiation under certain hypoxic conditions.

  18. Feasibility Study of Adjuvant Chemotherapy Using Taxane Plus Carboplatin for High-Risk Patients With Uterine Cervical Non-Squamous Cell Carcinoma After Radical Hysterectomy.

    Science.gov (United States)

    Sato, Seiya; Shimada, Muneaki; Ohta, Tsuyoshi; Kojimahara, Takanobu; Tokunaga, Hideki; Takano, Tadao; Yamaguchi, Satoshi; Tanabe, Hiroshi; Nishio, Shin; Kigawa, Junzo

    2016-03-01

    We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy. Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors. The patients were treated with 6 cycles of paclitaxel (PTX, 175 mg/m(2)) or docetaxel (DTX, 60 mg/m(2)) followed by CBDCA (area under the curve, 6) every 3 weeks. The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end point was the assessment of adverse events. Twenty-two patients received PTX/CBDCA (TC) chemotherapy, and the remaining 15 patients underwent DTX/CBDCA (DC) chemotherapy. The 2-year PFS rate was 62.1% (95% confidence interval, 44.6%-75.5%). Patients receiving DC chemotherapy showed a better 2-year PFS rate compared to those with TC chemotherapy, but the difference was not statistically significant (80.0% vs 50.0%, P = 0.1400). The most common grade 3/4 adverse events were hematologic toxicities, which were generally well tolerable. Nonhematologic toxicity was generally mild. Taxane and CBDCA combination chemotherapy, especially DC chemotherapy, may be one of the useful adjuvant treatments for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.

  19. Nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro.

    Science.gov (United States)

    Wang, Chengze; Gu, Weiting; Zhang, Yunpeng; Ji, Yawen; Wen, Yong; Xu, Xin

    2017-07-05

    Cigarette smoking is one of highly risk factors of cervical cancer. Recently nicotine has been reported to increase proliferation and invasion in some smoking related cancers, like non-small cell lung cancer and esophageal squamous cell cancer. However, the effects and mechanisms of nicotine stimulation on cervical cancer cells are not clear. Here, we investigated the effects and mechanisms of nicotine stimulation on HeLa cells in vitro. In our study, we found that nicotine could accelerate HeLa cells migration and invasion, activate PI3K/Akt and NF-κB pathways and increase the expression of Vimentin in vitro. Moreover, we demonstrated that the specific PI3K inhibitor LY294002 could reverse nicotine-induced cell migration and invasion, NF-κB activation and up-regulation of Vimentin. Inhibition of NF-κB by Pyrrolidine dithiocarbamate (PDTC) also antagonized nicotine-induced cell migration, invasion and up-regulation of Vimentin. Simply put, these findings suggest that nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Radiotherapeutic factors related to the control of cervical lymph node metastases in patients with oro- and hypopharyngeal carcinoma treated with chemoradiotherapy followed by planned neck dissection

    International Nuclear Information System (INIS)

    Fujii, Osamu; Ota, Yosuke; Kuwatsuka, Yoko

    2009-01-01

    To clarify radiotherapeutic factors related to the control of cervical lymph node metastases, we retrospectively reviewed 29 patients with N2-3 oro- and hypopharyngeal squamous cell carcinoma treated with chemoradiotherapy followed by planned neck dissection between April 2004 and March 2008. Pretreatment assessment of all patients revealed cervical metastases in a total of 63 neck levels. Planning target volume (PTV) was defined as lymph node metastases by neck level with a 5-mm margin, and a dose-volume histogram (DVH) was used to evaluate the maximum (PTV max), minimum (PTV min) and mean radiation dose to the PTV (PTV mean). Overall, 59% of the patients attained a pathologic complete response (pCR) in the neck. Evidence of residual pathologic tumor by neck level was found most commonly in Level V and retropharyngeal lymph nodes. On univariate analysis, primary site (oropharynx) and the effect of induction chemotherapy (partial response) were significant predictors of a neck disease specimen with negative pathology. PTV max and PTV mean in Level V were found to be significantly lower than those in Levels II and III. Furthermore, there was a significant association between radiation dose and pathologic status on the neck. Our data thus suggested that excellent dose coverage for cervical lymph nodes might lead to better regional control. (author)

  1. Radiosensitivity of drug-resistant human tumour xenografts

    International Nuclear Information System (INIS)

    Mattern, J.; Bak, M. Jr.; Volm, M.; Hoever, K.H.

    1989-01-01

    The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation. (orig.) [de

  2. An evidence on G2/M arrest, DNA damage and caspase mediated apoptotic effect of biosynthesized gold nanoparticles on human cervical carcinoma cells (HeLa)

    International Nuclear Information System (INIS)

    Jeyaraj, M.; Arun, R.; Sathishkumar, G.; MubarakAli, D.; Rajesh, M.; Sivanandhan, G.; Kapildev, G.; Manickavasagam, M.; Thajuddin, N.; Ganapathi, A.

    2014-01-01

    Highlights: • Gold nanoparticles (AuNPs) have been synthesized using Podophyllum hexandrum L. • AuNPs induces the oxidative stress to cell death in human cervical carcinoma cells. • It activates the caspase-cascade to cellular death. • It is actively blocks G2/M phase of cell cycle. - Abstract: Current prospect of nanobiotechnology involves in the greener synthesis of nanostructured materials particularly noble metal nanoparticles for various biomedical applications. In this study, biologically (Podophyllum hexandrum L.) synthesized crystalline gold nanoparticles (AuNPs) with the size range between 5 and 35 nm were screened for its anticancereous potential against human cervical carcinoma cells (HeLa). Stoichiometric proportion of the reaction mixture and conditions were optimized to attain stable nanoparticles with narrow size range. Different high throughput techniques like transmission electron microscope (TEM), X-ray diffraction (XRD) and UV–vis spectroscopy were adopted for the physio-chemical characterization of AuNPs. Additionally, Fourier transform infrared spectroscopy (FTIR) study revealed that the water soluble fractions present in the plant extract solely influences the reduction of AuNPs. Sublimely, synthesized AuNPs exhibits an effective in vitro anticancer activity against HeLa cells via induction of cell cycle arrest and DNA damage. Furthermore, it was evidenced that AuNPs treated cells are undergone apoptosis through the activation of caspase cascade which subsequently leads to mitochondrial dysfunction. Thereby, this study proves that biogenic colloidal AuNPs can be developed as a promising drug candidature for human cervical cancer therapy

  3. Cytotoxic activity of proteins isolated from extracts of Corydalis cava tubers in human cervical carcinoma HeLa cells

    Directory of Open Access Journals (Sweden)

    Balcerkiewicz Stanislaw

    2010-12-01

    Full Text Available Abstract Background Corydalis cava Schweigg. & Koerte, the plant of numerous pharmacological activities, together with the studied earlier by our group Chelidonium majus L. (Greater Celandine, belong to the family Papaveraceae. The plant grows in Central and South Europe and produces the sizeable subterraneous tubers, empty inside, which are extremely resistant to various pathogen attacks. The Corydalis sp. tubers are a rich source of many biologically active substances, with the extensive use in European and Asian folk medicine. They have analgetic, sedating, narcotic, anti-inflammatory, anti-allergic and anti-tumour activities. On the other hand, there is no information about possible biological activities of proteins contained in Corydalis cava tubers. Methods Nucleolytic proteins were isolated from the tubers of C. cava by separation on a heparin column and tested for DNase activity. Protein fractions showing nucleolytic activity were tested for cytotoxic activity in human cervical carcinoma HeLa cells. Cultures of HeLa cells were conducted in the presence of three protein concentrations: 42, 83 and 167 ng/ml during 48 h. Viability of cell cultures was appraised using XTT colorimetric test. Protein fractions were separated and protein bands were excised and sent for identification by mass spectrometry (LC-ESI-MS/MS. Results The studied protein fractions showed an inhibiting effect on mitochondrial activity of HeLa cells, depending on the administered dose of proteins. The most pronounced effect was obtained with the highest concentration of the protein (167 ng/ml - 43.45 ± 3% mitochondrial activity of HeLa cells were inhibited. Mass spectrometry results for the proteins of applied fractions showed that they contained plant defense- and pathogenesis-related (PR proteins. Conclusions The cytotoxic effect of studied proteins toward HeLa cell line cells has been evident and dependent on increasing dose of the protein. The present study, most

  4. Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    McDowell, Lachlan J.; Huang, Shao Hui [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Xu, Wei; Che, Jiahua [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Wong, Rebecca K.S.; Brierley, James; Kim, John; Cummings, Bernard; Waldron, John; Bayley, Andrew [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Hansen, Aaron [Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Department of Otolaryngology–Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Ringash, Jolie, E-mail: jolie.ringash@rmp.uhn.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2017-05-01

    Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

  5. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    Science.gov (United States)

    2018-02-14

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer AJCC v6 and v7; Stage IA2 Cervical Cancer AJCC v6 and v7; Stage IB1 Cervical Cancer AJCC v6 and v7

  6. Cervical syphilitic lesions mimicking cervical cancer: a rare case report

    Directory of Open Access Journals (Sweden)

    Xiaoqing Zhu

    2015-02-01

    Full Text Available A woman presented to the hospital due to postcoital vaginal bleeding. The patient was initially diagnosed with cervical carcinoma by clinicians at a local hospital. However, a biopsy of the cervical lesions revealed chronic inflammation and erosion of the cervical mucosa, and the rapid plasma reagin ratio titer was 1:256. The patient was eventually diagnosed with syphilitic cervicitis and treated with minocycline 0.1 g twice a day. The patient was cured with this treatment.

  7. Prognostic significance of CD24 protein expression in patients treated with adjuvant radiotherapy after radical hysterectomy for cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sung, Chang Ohk; Park, Won; Choi, Yoon-La; Ahn, Geunghwan; Song, Sang Yong; Huh, Seung Jae; Bae, Duk Soo; Kim, Byoung Gie; Lee, Je Ho

    2010-01-01

    Background and purpose: The CD24 marker is expressed in various carcinomas and is associated with shorter survival rates. We evaluated the prognostic significance of CD24 protein overexpression in patients treated with post-operative radiotherapy (RT) after surgery, and its prognostic significance and specific role stratified by adjuvant treatment modalities. Materials and methods: We determined the CD24 expression status of 140 patients with cervical squamous cell carcinoma treated with RT alone or with chemoradiotherapy (CRT) after radical hysterectomy procedures. Results: CD24 expression was detected in 59 patients (42%) and was significantly associated with locoregional failure-free survival (LRFFS) (p = 0.0218), distant metastasis-free survival (DMFS) (p = 0.0001), and overall survival (OS) (p = 0.0053). In the multivariate analysis, CD24 positivity was also significantly associated with DMFS (p = 0.025) and OS (p = 0.045). CD24 expression stratified by post-operative treatments (CRT or RT alone) was associated with DMFS (p = 0.0001) but not with LRFFS (p = 0.4423) in the CRT group. However, CD24 expression was associated with LRFFS (p = 0.0198) but not with DMFS (p = 0.5269) in the RT alone group. Conclusions: CD24 expression is an independent prognostic marker in patients with cervical squamous cell carcinoma, even adjuvant treatment after surgery. And this study reveals different prognostic role of CD24 expression in two subgroups treated differently after surgery. Therefore, new therapeutic strategies targeting CD24 expression stratified by subgroups might have important clinical implications.

  8. High grade serous ovarian carcinoma with serous tubal intraepithelial carcinoma in a case presented with atypical glandular cell favor neoplasm cervical cytology and dermatomyositis

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    Mun-Kun Hong

    2015-04-01

    Conclusion: The patient had serous carcinoma of the ovary with tubal STIC, which presented as dermatomyositis. The AGC-FN identified from a Pap smear hinted at a diagnosis of ovarian carcinoma. These presentations point to an occult malignancy in the genital tract and demand careful diagnostic workup.

  9. Distribution of human papilloma virus genotype prevalence in invasive cervical carcinomas and precancerous lesions in the Yangtze River Delta area, China.

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    Wang, Hongyun; Cheng, Xiaodong; Ye, Jing; Xu, Xiuyun; Hong, Ying; Sui, Long; You, Zhixue; Xie, Xing

    2018-04-27

    This study aimed to provide more information for cancer prevention strategies by determining the distribution of human papilloma virus (HPV) genotype prevalence in invasive cervical carcinoma (ICC) and precancerous lesion patients in the Yangtze River Delta area in China. This multi-centre descriptive cross-sectional study involves four university hospitals in the Jiangzhehu area. Women with histologically confirmed cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3 or ICC who were diagnosed and treated in the four selected hospitals between February 2012 and April 2014 were eligible for recruitment. The average age of the patients was 40.93 ± 11.87 years old, among whom the youngest was 17 years old and the oldest was 76 years old.Those with immunodeficiency diseases or a previous history of cancer or CIN were excluded. HPV genotyping was performed by a central laboratory. The distribution and age and disease specificity of the HPV genotype prevalence were analysed. Of the 2181 collected samples, 251 were ICC and 1930 were CIN. The mean age of cervical cancer and CIN patients was 40.93 ± 11.8 years (range, 17-76 years). The five most commonly identified HPV types in each lesion class were as follows: CIN1: 52, 58, 16, 33, and CP; CIN2: 16, 58, 52, 33, and 31; CIN3: 16, 58, 33, 52, and 31; and ICC: 16, 58, 18, 52, and 33. CIN1 had an earlier age of onset (30-40 years) than CIN2, CIN3, and cervical cancer. The age of onset of cervical cancer exhibited two peaks at 40-44 and 50-54 years of age. In all infected patients, the frequency of HPV infection with a single type was 62.9%, and with multiple types, it was 38.1%. There was no difference in the frequencies of multiple types amongst the different cervical lesions. The most prevalent genotypes in the investigated area (52, 58, 16 and 18) justify the necessity of anti-HPV vaccination in teenagers and young girls under 24 years old in the Yangtze River Delta area in China. Infection with

  10. Prognostic Significance of Vascular Endothelial Growth Factor (VEGF and Her-2 Protein in the Genesis of Cervical Carcinoma

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    Arshad H. Rahmani

    2018-02-01

    CONCLUSION: The present study supports earlier findings that over-expression / up-regulation of VEGF and Her - 2 is linked with poor prognosis and may play a vital role in the development and progression of cervical cancer.

  11. Uterine cervical carcinoma: a comparison of two- and three-dimensional T2-weighted turbo spin-echo MR imaging at 3.0 T for image quality and local-regional staging

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Y.R. [The Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, 222, Banpo-daero, Seocho-gu, Seoul (Korea, Republic of); The Catholic University of Korea, Department of Radiology, Incheon St. Mary' s Hospital, College of Medicine, Bupyeong 6-dong, Bupyeong-gu, Incheon (Korea, Republic of); Rha, S.E.; Choi, B.G.; Oh, S.N.; Park, M.Y.; Byun, J.Y. [The Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, 222, Banpo-daero, Seocho-gu, Seoul (Korea, Republic of)

    2013-04-15

    To compare three-dimensional (3D) T2-weighted turbo spin-echo (TSE) with multiplanar two-dimensional (2D) T2-weighted TSE for the evaluation of invasive cervical carcinoma. Seventy-five patients with cervical carcinoma underwent MRI of the pelvis at 3.0 T, using both 5-mm-thick multiplanar 2D (total acquisition time = 12 min 25 s) and 1-mm-thick coronal 3D T2-weighted TSE sequences (7 min 20 s). Quantitative analysis of signal-to-noise ratio (SNR) and qualitative analysis of image quality were performed. Local-regional staging was performed in 45 patients who underwent radical hysterectomy. The estimated SNR of cervical carcinoma and the relative tumour contrast were significantly higher on 3D imaging (P < 0.0001). Tumour conspicuity was better with the 3D sequence, but the sharpness of tumour margin was better with the 2D sequence. No significant difference in overall image quality was noted between the two sequences (P = 0.38). There were no significant differences in terms of the diagnostic accuracy, sensitivity, and specificity of parametrial invasion, vaginal invasion, and lymph node metastases. Multiplanar reconstruction 3D T2-weighted imaging is largely equivalent to 2D T2-weighted imaging for overall image quality and staging accuracy of cervical carcinoma with a shorter MR data acquisition, but has limitations with regard to the sharpness of the tumour margin. circle 3D T2-weighted MR sequence is equivalent to 2D for cervical carcinoma staging. (orig.)

  12. Efficacy of qualitative response assessment interpretation criteria at 18F-FDG PET-CT for predicting outcome in locally advanced cervical carcinoma treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Scarsbrook, Andrew; Vaidyanathan, Sriram; Chowdhury, Fahmid; Patel, Chirag; Swift, Sarah; Cooper, Rachel

    2017-01-01

    To evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome. Ninety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test. Forty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4). 11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death (P < 0.001). Use of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced

  13. Efficacy of qualitative response assessment interpretation criteria at 18F-FDG PET-CT for predicting outcome in locally advanced cervical carcinoma treated with chemoradiotherapy

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    Scarsbrook, Andrew [Leeds Teaching Hospitals NHS Trust, Department of Radiology, Leeds (United Kingdom); Leeds Teaching Hospitals NHS Trust, Department of Nuclear Medicine, Level 1, Bexley Wing, St James' s University Hospital, Leeds (United Kingdom); University of Leeds, Leeds Institute of Cancer and Pathology, Leeds (United Kingdom); Vaidyanathan, Sriram; Chowdhury, Fahmid; Patel, Chirag [Leeds Teaching Hospitals NHS Trust, Department of Radiology, Leeds (United Kingdom); Leeds Teaching Hospitals NHS Trust, Department of Nuclear Medicine, Level 1, Bexley Wing, St James' s University Hospital, Leeds (United Kingdom); Swift, Sarah [Leeds Teaching Hospitals NHS Trust, Department of Radiology, Leeds (United Kingdom); Cooper, Rachel [Leeds Teaching Hospitals NHS Trust, Department of Clinical Oncology, Leeds (United Kingdom)

    2017-04-15

    To evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome. Ninety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test. Forty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4). 11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death (P < 0.001). Use of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced

  14. Randomized Comparison of Intra-Arterial Chemotherapy Versus Intra-Arterial Chemotherapy and Gelfoam Embolization for Treatment of Advanced Cervical Carcinoma

    International Nuclear Information System (INIS)

    Ikeda, O.; Mizukami, N.; Murata, Y.; Arakawa, A.; Katabuchi, H.; Okamoto, H.; Yasunaga, T.; Tsunawaki, A.; Yamashita, Y.

    2005-01-01

    Purpose:We evaluated the effects of intra-arterial infusion therapy by comparing the results obtained with a combination of intra-arterial anticancer drugs with and without transcatheter arterial embolization (TAE) in patients with cervical cancer.Methods:Between April 1999 and March 2003, intra-arterial therapy was administered to 45 patients (mean age 49 years) with cervical cancer. Of these, 18 had stage IIb , 4 had stage IIIa, 19 had stage IIIb, and 4 had stage IVb cancer; the histopathologic types were squamous cell carcinoma (n = 35), adenocarcinoma (n = 8), and adenosquamous carcinoma (n = 2). A total of 45 patients gave their informed consent and were randomized on a continuous basis into one of three groups according to the therapeutic protocols: group A consisted of 15 patients who received cisplatin, group B consisted of 17 patients who received cisplatin, mitomycin, doxorubicin hydrochloride, and 5-fluorouracil, and group C consisted of 13 patients who received cisplatin and TAE. Each protocol was administered twice with a 3 week interval between treatments. The efficacy of treatment was evaluated on the basis of the tumor reduction ratio (%) using MR imaging and the side effects were analyzed.Results:In groups A, B, and C, the tumor reduction ratio was 54%, 84%, and 86%, respectively; it was significantly greater in groups B and C than in group A (p < 0.01). The difference between groups B and C was not statistically significant. Although all group C patients developed severe pain after TAE, the pain was controlled with analgesics. Thrombocytopenia occurred in 6 of 17 (35%) group B patients.Conclusion:Group B and C patients had better tumor reduction than those in group A. Fewer hematologic complications occurred in group C patients compared with group B

  15. Cervical adenocarcinoma

    International Nuclear Information System (INIS)

    Raymond, P.E.; Bonenfant, J.L.; Blais, R.

    1988-01-01

    Glandular neoplasms of the uterine cervix represent a small but important group of cervical carcinomas. Included in the present study were 68 cases of primary adenocarcinomas of the uterine cervix seen from 1972 to 1986 in our Radiation Oncology Center. The complete data set for all patients was analyzed with regard to symptoms, histologic patterns, diagnostic procedures, treatment methods, and prognosis. The authors stress the importance of establishing the primary origin of the lesion in the cervix and of completely investigating patients with an abnormal bleeding pattern, even those with an apparently normal exocervix

  16. In vitro radiosensitization of human cervical carcinoma cells by combined use of 13-cis-retinoic acid and interferon-α2a

    International Nuclear Information System (INIS)

    Ryu, Samuel; Kim, Ok Bae; Kim, Sang-Hie; He, Shao Quin; Kim, Jae Ho

    1998-01-01

    Background: Significant antitumor activity has been reported with the combined use of 13-cis-retinoic acid (cRA) and interferon-α2a (IFN-α) in the treatment of advanced-stage cervical cancers and skin cancers. Since IFN-α has been shown to be a modest radiation enhancer for selected malignant tumor cells and the cytotoxic activity is more enhanced by combining cRA and IFN-α, we hypothesized that the exposure of selected human carcinoma cells to combined cRA and IFN-α would render the cells highly radiosensitive. Methods and Materials: Two human cervical carcinoma cell lines, ME-180 and HeLa-S3, were chosen for the present study because of the different characteristics of the retinoic acid receptor status of the cell lines. To demonstrate the effects of combined cRA and IFN-α treatment on radiation response, we exposed the cells to cRA, IFN-α, or a combination of the drugs for 72 h before radiation. Experiments were carried out at minimally cytotoxic concentrations of the drug for radiation studies. End points of the study were cell growth inhibition and clonogenic ability of the single-plated cells. Effects of cRA and IFN-α on radiation response were quantitatively analyzed by constructing the radiation cell survival curves of ME-180 and HeLa cells. Results: ME-180 cells exhibited varying degrees of cytotoxicity with cRA and IFN-α, while HeLa cells showed no toxic effects with the same treatment. Combined treatment of cRA and IFN-α produced an additive cytotoxic effect in ME-180 cells. Radiosensitization was minimal when ME-180 cells were treated with either cRA or IFN-α before radiation. When ME-180 cells were exposed to 10 μM cRA for 48 h and 1000 U/ml IFN-α for 24 h prior to radiation, there was a significant enhancement in radiation-induced cell killing; the dose modification factor was 2.1 ± 0.9 at the 1% cell-survival level. On the other hand, HeLa-S3 cells exhibited no increased cytotoxicity or radiation enhancement under the same experimental

  17. Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy.

    Science.gov (United States)

    Kaliff, Malin; Sorbe, Bengt; Mordhorst, Louise Bohr; Helenius, Gisela; Karlsson, Mats G; Lillsunde-Larsson, Gabriella

    2018-04-10

    Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

  18. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection

    International Nuclear Information System (INIS)

    Erkal, Haldun S.; Mendenhall, William M.; Amdur, Robert J.; Villaret, Douglas B.; Stringer, Scott P.

    2001-01-01

    Purpose: The present study presents the experience at the University of Florida with treatment of patients with squamous cell carcinomas (SCC) metastatic to cervical lymph nodes from an unknown head-and-neck mucosal (H and NM) site with radiotherapy (RT) alone or in combination with neck dissection (ND). Methods and Materials: The study included 126 patients treated with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. Results: Twelve patients (10%) developed SCC in H and NM sites at 0.5 to 10.9 years (median, 1.8 years). The rate of developing carcinomas in H and NM sites at 5 years was 13%. Histologic differentiation significantly affected the rate of developing carcinomas in H and NM sites in multivariate analysis. Sixteen patients (13%) had persistent nodal disease and 12 patients (10%) developed recurrent nodal disease at 0.5 to 10.9 years (median, 1.1 years). The nodal control rate at 5 years was 78%. Nodal size, N stage, and planned ND significantly affected the rate of nodal control in multivariate analysis. Nineteen patients (15%) developed distant metastasis at 0.2-5.1 years (median, 0.9 years). The distant metastases rate at 5 years was 14%. Extracapsular extension and RT dose significantly affected the risk of distant metastases in multivariate analysis. The overall absolute survival rate at 5 years was 47%. Extracapsular extension, N stage, RT dose for H and NM sites, and planned ND significantly affected absolute survival in multivariate analysis. The rate of cause-specific survival at 5 years was 67%. Extracapsular extension, nodal size, N stage, overall treatment time, and planned ND significantly affected cause-specific survival in multivariate analysis. Eight patients (6%) had severe postoperative complications and 6 patients (5%) had severe late complications. Conclusion: The present study supports the effectiveness of RT in lowering the rate of developing carcinomas in the H

  19. The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: Evidence suggestive of consequential late effect (CQLE)

    International Nuclear Information System (INIS)

    Wang, C.-J.; Leung, Stephen Wan; Chen, H.-C.; Sun, L.-M.; Fang, F.-M.; Huang, E.-Y.; Hsiung, C.-Y.; Changchien, C.-C.

    1998-01-01

    Purpose: To correlate the acute toxicity during pelvic irradiation and the development of late rectal injury following radiation therapy for cervical carcinoma. Methods and Materials: Two hundred and twenty patients treated with curative-intent radiation therapy between November 1987 and January 1992 were analyzed. Patients were treated initially with external beam irradiation, 40-44 Gy/20-22 fractions to whole pelvis, followed by high dose rate intracavitary brachytherapy, 7.2 Gy to point A for 3 fractions. Severity of diarrhea during radiation therapy was scored according to six criteria: fecal characteristics, frequency, onset, prescription of antidiarrheal agents, body weight loss during irradiation, and extramedical care needed. Patients were categorized as group ND (no obvious diarrhea), group MD (moderate diarrhea), and group SD (severe diarrhea) for sum score 0-1, 2-5, and ≥6, respectively. The rate of radiation proctitis was expressed, analyzed, and compared with actuarial proctitis-free rate and prevalence. Results: 1) According to the score, 76 (35%), 89 (40%), and 55 (25%) patients were categorized as group ND, group MD, and group SD, respectively. Distribution of patients and treatment characteristics among the three groups appeared similar. Patients treated with a larger field size, ≥16.5 cm 2 , tended to have increased severity of diarrhea. 2) Overall, 103 patients (47%, 103 of 220) developed radiation proctitis. Twenty-one patients were in group ND (28%, 21 of 76), 43 in group MD (48%, 43 of 89), and 39 in group SD (71%, 39 of 55). 3) The five-year actuarial proctitis-free rate was 72, 52, and 29% for group ND, MD, and SD, respectively (p s = 0.229, p = 0.098). 6) Cox's multivariate analysis revealed that severity of diarrhea was the only factor that significantly correlated with the development of radiation proctitis. Conclusion: Patients with increased acute toxicity and diarrhea during radiation therapy of cervical carcinoma significantly

  20. Carboplatin selective intra-arterial infusion chemotherapy with concurrent radiotherapy on cervical lymph node metastasis in squamous cell carcinoma in the oral region

    International Nuclear Information System (INIS)

    Kuang, Hai; Sunakawa, Hajime; Arasaki, Akira; Arakaki, Keiichi; Nakasone, Toshiyuki; Ueda, Gosei; Gibo, Masaki

    2005-01-01

    In this retrospective study, we evaluated the effect of carboplatin (CBDCA) selective intra-arterial infusion chemotherapy with concurrent radiotherapy (SIACR) on cervical lymph node metastasis in patients with squamous cell carcinoma in the oral region, and determined the factors related to this effect. Twenty seven patients were enrolled with biopsy-proven squamous cell carcinoma of the oral region. They received CBDCA SIACR for cervical lymph node metastasis and underwent neck dissection. For all patients, 38 metastatic lymph nodes were diagnosed using a number of criteria. The short-axis diameters of lymph nodes were measured on CT images before and after SIACR. All metastatic lymph nodes were histologically classified into complete, good, or poor responses according to their histological features. Level I metastatic lymph nodes were classified as proximal or distal according to the position of the tip of the microcatheter in the feeding artery. In 9 of 27 patients, computed tomography angiography (CTA) was performed to evaluate the vascularity and extent of the primary tumor and metastatic lymph nodes. The reduction percentage of lymph node short-axis diameters was 0%-58.3% with a mean of 26%. Complete response nodes (36%±12%) showed a significant reduction in short-axis diameters compared with good (24%±15%) and poor (27%±11%) response nodes (P<0.05). In the proximal group, 0, 5 (63%) and 3 (37%) lymph nodes exhibited complete, good and poor responses. In the distal group, 4 (44%), 5 (56%) and 0 lymph nodes exhibited complete, good and poor responses. The difference between the proximal and distal groups' histological response was statistically significant (P<0.05). No lymph nodes identified by CTA exhibited a poor response. A correlation between reduction in short-axis diameters of lymph nodes and histological responses was demonstrated in which reduction rates increased with histological response. Findings indicated that histological response was greater

  1. Transforming Growth Factor β1 Could Influence Thyroid Nodule Elasticity and Also Improve Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Li, Yi; Wang, Yan; Wu, Qiong; Hu, Bing

    2015-11-01

    Ultrasound elastography has been a very useful tool in predicting the risk of malignant thyroid tumor for several years. The objective of this study was to determine if there is a correlation between strain ratio (SR), collagen deposition and transforming growth factor β1 (TGF-β1) expression in different types of thyroid nodules and if TGF-β1 is related to cervical lymph node metastasis. 102 nodules from 81 patients who underwent thyroid resection surgery in our hospital were retrospectively studied. All of these patients had undergone ultrasound elastography scanning before surgery. Masson staining and immunohistochemical staining were used to evaluate the ratio of expression of collagen deposition and TGF-β1. There was a significant difference between benign and malignant thyroid nodules in SR (8.913 ± 11.021 vs. 1.732 ± 0.727, p = 0.000), collagen content (0.371 ± 0.125 vs. 0.208 ± 0.057, p = 0.000) and TGF-β1 expression (0.336 ± 0.093 vs. 0.178 ± 0.071, p = 0.000). A cutoff of 2.99 for SR measurement was selected for the highest Youden index for predicting malignant thyroid nodules, which yielded 87.88% sensitivity, 100% specificity, 100% positive predictive value, 83.72% negative predictive value and 92.15% accuracy. Expression of collagen and TGF-β1 was positively correlated with SR measurements (coefficient = 0.839 for collagen and 0.855 for TGF-β1, p = 0.000). Among 61 nodules with papillary thyroid carcinoma, the average SR for the metastasis group was higher than that for the non-metastasis group (10.955 ± 13.805 and 7.852 ± 7.931, respectively), but without statistical significance (p = 0.287). Collagen deposition was significantly higher in the metastasis group than in the non-metastasis group (0.421 ± 0.091 vs. 0.353 ± 0.118, p = 0.011). TGF-β1 expression was also significantly higher in the metastasis group than in the non-metastasis group (0.378 ± 0.0.69 vs. 0.328 ± 0.091, p = 0.016). To conclude, TGF-β1 may contribute to thyroid

  2. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    Directory of Open Access Journals (Sweden)

    Takatori E

    2016-09-01

    Full Text Available Eriko Takatori, Tadahiro Shoji, Anna Takada, Takayuki Nagasawa, Hideo Omi, Masahiro Kagabu, Tatsuya Honda, Fumiharu Miura, Satoshi Takeuchi, Toru Sugiyama Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Iwate, Japan Objective: In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group with patients who underwent RH without NAC (Ope group. Patients and methods: The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS and overall survival (OS between the groups. Results: There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days in the NAC group and 25 days (21–34 days in the Ope group; the patients in the NAC group were discharged earlier (P=0.032. The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91, and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028. Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24, and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101. Conclusion: NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous

  3. Cervical Cap

    Science.gov (United States)

    ... Videos for Educators Search English Español The Cervical Cap KidsHealth / For Teens / The Cervical Cap What's in ... Call the Doctor? Print What Is a Cervical Cap? A cervical cap is a small cup made ...

  4. Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid*

    Science.gov (United States)

    Yue, Qingxi; Feng, Lixing; Cao, Biyin; Liu, Miao; Zhang, Dongmei; Wu, Wanying; Jiang, Baohong; Yang, Min; Liu, Xuan; Guo, Dean

    2016-01-01

    Gambogic acid (GA) is an anticancer agent in phase IIb clinical trial in China. In HeLa cells, GA inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis, as showed by results of MTT assay and flow cytometric analysis. Possible target-related proteins of GA were searched using comparative proteomic analysis (2-DE) and nine proteins at early (3 h) stage together with nine proteins at late (24 h) stage were found. Vimentin was the only target-related protein found at both early and late stage. Results of both 2-DE analysis and Western blotting assay suggested cleavage of vimentin induced by GA. MS/MS analysis of cleaved vimentin peptides indicated possible cleavage sites of vimentin at or near ser51 and glu425. Results of targeted proteomic analysis showed that GA induced change in phosphorylation state of the vimentin head domain (aa51–64). Caspase inhibitors could not abrogate GA-induced cleavage of vimentin. Over-expression of vimentin ameliorated cytotoxicity of GA in HeLa cells. The GA-activated signal transduction, from p38 MAPK, heat shock protein 27 (HSP27), vimentin, dysfunction of cytoskeleton, to cell death, was predicted and then confirmed. Results of animal study showed that GA treatment inhibited tumor growth in HeLa tumor-bearing mice and cleavage of vimentin could be observed in tumor xenografts of GA-treated animals. Results of immunohistochemical staining also showed down-regulated vimentin level in tumor xenografts of GA-treated animals. Furthermore, compared with cytotoxicity of GA in HeLa cells, cytotoxicity of GA in MCF-7 cells with low level of vimentin was weaker whereas cytotoxicity of GA in MG-63 cells with high level of vimentin was stronger. These results indicated the important role of vimentin in the cytotoxicity of GA. The effects of GA on vimentin and other epithelial-to-mesenchymal transition (EMT) markers provided suggestion for better usage of GA in clinic. PMID:26499837

  5. B-Flow Twinkling Sign in Preoperative Evaluation of Cervical Lymph Nodes in Patients with Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Giuseppina Napolitano

    2013-01-01

    Full Text Available Papillary thyroid cancer (PTC is the most common histologic type of differentiated thyroid cancer. The first site of metastasis is the cervical lymph nodes (LNs. The ultrasonography (US is the best diagnostic method for the detection of cervical metastatic LNs. We use a new technique, B-flow imaging (BFI, recently used for evaluation of thyroid nodules, to estimate the presence of BFI twinkling signs (BFI-TS, within metastatic LNs in patients with PTC. Two hundred and fifty-two patients with known PTC were examined for preoperative evaluation with conventional US and BFI. Only 83 with at least one metastatic LN were included. All patients included underwent surgery; the final diagnosis was based on the results of histology. The following LN characteristics were evaluated: shape, abnormal echogenicity, absent hilum, calcifications, cystic appearance, peripheral vascularization, and BFI-TS. A total of 604 LNs were analyzed. Of these, 298 were metastatic, according to histopathology. The BFI-TS showed high values ​​of specificity (99.7% and sensitivity (80.9%. The combination of each conventional US sign with the BF-TS increases the specificity. Our findings suggest that BFI can be helpful in the selection of suspicious neck LNs that should be examined at cytologic examination for accurate preoperative staging and individual therapy selection.

  6. Mapping the extent of disease by multislice computed tomography, magnetic resonance imaging and sentinel node evaluation in stage I and II cervical carcinoma

    Directory of Open Access Journals (Sweden)

    Rajaram S

    2010-01-01

    Full Text Available Aims: (1 To map the extent of disease in women with stage I and II carcinoma cervix by multislice spiral computed tomography (CT, magnetic resonance imaging (MRI and sentinel nodes. (2 To assess accuracy of each modality individually and in conjunction with FIGO clinical staging. Design and Setting: Prospective, single-blind study. Departments of Obstetrics and Gynaecology, Radiodiagnosis, and Pathology, UCMS and GTBH and Division of Radiological Imaging and Bioinformatics, INMAS, Delhi. Material and Method: The study was conducted on 25 women with cervical cancer FIGO stage I and II. Each woman underwent clinical staging, multislice spiral CT and MRI which was compared to the gold-standard histopathology/cytology. The overall accuracy of each modality and improvement of clinical staging by CT/MRI were noted. Sentinel nodes were evaluated by intracervical Patent Blue V dye injection. Statistical Analysis: Sensitivity, specificity, positive and negative predictive values were calculated by 2Χ2 contingency tables. Results: The accuracy of staging by FIGO, CT and MRI was 68%, 52% and 80%, respectively. MRI and CT improved the overall accuracy of FIGO staging to 96% and 80%, respectively. Sentinel nodes were identified in 89% of patients with 91% accuracy. Conclusion: MRI emerges as the most valuable stand-alone modality improving accuracy of FIGO staging to 96%. Sentinel lymph-node evaluation appears promising in evaluating spread beyond cervix.

  7. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    International Nuclear Information System (INIS)

    Zacapala-Gómez, Ana Elvira; Del Moral-Hernández, Oscar; Villegas-Sepúlveda, Nicolás; Hidalgo-Miranda, Alfredo; Romero-Córdoba, Sandra Lorena

    2016-01-01

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  8. Albert-Lembert versus hybrid-layered suture in hand sewn end-to-end cervical esophagogastric anastomosis after esophageal squamous cell carcinoma resection.

    Science.gov (United States)

    Feng, Fan; Sun, Li; Xu, Guanghui; Hong, Liu; Yang, Jianjun; Cai, Lei; Li, Guocai; Guo, Man; Lian, Xiao; Zhang, Hongwei

    2015-11-01

    Hand sewn cervical esophagogastric anastomosis (CEGA) is regarded as preferred technique by surgeons after esophagectomy. However, considering the anastomotic leakage and stricture, the optimal technique for performing this anastomosis is still under debate. Between November 2010 and September 2012, 230 patients who underwent esophagectomy with hand sewn end-to-end (ETE) CEGA for esophageal squamous cell carcinoma (ESCC) were analyzed retrospectively, including 111 patients underwent Albert-Lembert suture anastomosis and 119 patients underwent hybrid-layered suture anastomosis. Anastomosis construction time was recorded during operation. Anastomotic leakage was recorded through upper gastrointestinal water-soluble contrast examination. Anastomotic stricture was recorded during follow up. The hybrid-layered suture was faster than Albert-Lembert suture (29.40±1.24 min vs. 33.83±1.41 min, P=0.02). The overall anastomotic leak rate was 7.82%, the leak rate in hybrid-layered suture group was significantly lower than that in Albert-Lembert suture group (3.36% vs. 12.61%, P=0.01). The overall anastomotic stricture rate was 9.13%, the stricture rate in hybrid-layered suture group was significantly lower than that in Albert-Lembert suture group (5.04% vs. 13.51%, P=0.04). Hand sewn ETE CEGA with hybrid-layered suture is associated with lower anastomotic leakage and stricture rate compared to hand sewn ETE CEGA with Albert-Lembert suture.

  9. Multiple fractions of gamma rays do not induce overexpression of c-myc or c-Ki-ras oncogenes in human cervical carcinoma cells

    International Nuclear Information System (INIS)

    Osmak, M.; Soric, J.; Matulic, M.

    1993-01-01

    Multiple fractions of gamma rays (0.5 Gy daily, 30 fractions) had previously been found to change the sensitivity of human cervical carcinoma HeLa cells to anticancer drugs. Preirradiated cells became resistant to cisplatin, methotrexate and vincristine but retained the same sensitivity to gamma rays and ultraviolet light. Some mechanisms involved in the resistance of preirradiated cells to cisplatin and vincristine were determined, i.e. the increased levels of metallothioneins and increased expression of plasma membrane P glycoprotein. As recent reports indicated that the resistance to cisplatin and ionizing radiation may involve the expression of oncogenes, the problem was studied whether multiple fractions of gamma rays can change the expression of c-myc and c-Ki-ras oncogenes in HeLa cells and whether there is a correlation between the expression of these oncogenes and the sensitivity of preirradiated cells to cisplatin and gamma rays. The expression of c-myc and c-Ki-ras oncogenes was examined using the DNA dot blot, the RNA dot blot and Northern blot analysis. The results show that preirradiation induced neither amplification nor elevated expression of c-myc and c-Ki-ras oncogenes. Furthermore, there is no correlation between the expression of c-myc and c-Ki-ras oncogenes and the acquired resistance to cisplatin. (author) 3 figs., 32 refs

  10. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    Energy Technology Data Exchange (ETDEWEB)

    Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx [Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D.F., México (Mexico); Hidalgo-Miranda, Alfredo, E-mail: ahidalgo@inmegen.gob.mx [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); Romero-Córdoba, Sandra Lorena, E-mail: sromero_cordoba@hotmail.com [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); and others

    2016-01-15

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  11. Expression of cancer stem markers could be influenced by silencing of p16 gene in HeLa cervical carcinoma cells.

    Science.gov (United States)

    Wu, H; Zhang, J; Shi, H

    2016-01-01

    Effect of the tumor suppression gene p16 on the biological characteristics of HeLa cervical carcinoma cells was explored. The expression of p16 protein was increased in HeLa tumor sphere cells, and no significant difference in tumor spheres from the first to the fourth passages. Compared with those of parental HeLa cells, the proportion of CD44+/CD24- and ABCG2+ cells increased significantly in tumor spheres. However after the cells were silenced by the p16-sh289 vector, expression of P16 protein and the cell number of CD44+/CD24- and ABCG2+ decreased. Moreover, HeLa cells with p16 gene silencing showed decreased abilities of sphere formation and matrigel invasion. More HeLa cells with p16 gene silence were needed for tumor formation in nude mice. Tumor size and weight in mouse model established with p16 gene silenced HeLa cells were less than those with HeLa parental cell model. The present results indicate that silencing of the p16 gene inhibits expression of cancer stem cell markers and tumorigenic ability of HeLa cells.

  12. A survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer

    International Nuclear Information System (INIS)

    Coucke, P.A.; Ciernik, I.F.; Maingon, P.; Do, H.P.

    2000-01-01

    The treatment outcome of advanced stage uterine cervical carcinoma remains unsatisfactory. In order to elaborate a novel trial within The Radiotherapy Cooperative Group (RCG) of the European Organization for Research and Treatment of Cancer (EORTC), we conducted a survey in 1997-1998 to determine the variability of pre-treatment assessment and treatment options. The variability of choosing surgery, defined radiation therapy techniques and chemotherapy are investigated, as well as the center's choices of future treatment strategies. Fifty two of 81 RCG centers from the RCG have participated in the survey. As one would expect, there is a large variation in the techniques used for pretreatment evaluation and treatment options. There is no 'standard' for reporting acute and late side effects. Chemotherapy is used neither systematically nor uniformly, and some centers continue to use neadjuvant chemotherapy modalities. Furthermore, the survey reveals that there is a strong demand for the reduction of overall treatment-time, for clinical investigation of novel combined modality treatment strategies, especially chemo-radiation therapy, and also for the use of new radiation sensitizers. We conclude that a more homogeneous approach to the pretreatment evaluation as well as treatment techniques is required in order to allow adequate quality control in any future trial of the RCG in the EORTC. (author)

  13. Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico

    Science.gov (United States)

    López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

    2009-01-01

    Background In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Results Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. Conclusion We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype. PMID:19216802

  14. Poor Prognosis Associated With Human Papillomavirus α7 Genotypes in Cervical Carcinoma Cannot Be Explained by Intrinsic Radiosensitivity

    International Nuclear Information System (INIS)

    Hall, John S.; Iype, Rohan; Armenoult, Lucile S.C.; Taylor, Janet; Miller, Crispin J.; Davidson, Susan; Sanjose, Silvia de; Bosch, Xavier; Stern, Peter L.; West, Catharine M.L.

    2013-01-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity. Methods and Materials: HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA 25 ) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays. Results: Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14). Conclusion: The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity

  15. Poor Prognosis Associated With Human Papillomavirus α7 Genotypes in Cervical Carcinoma Cannot Be Explained by Intrinsic Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Hall, John S.; Iype, Rohan; Armenoult, Lucile S.C. [Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom); Taylor, Janet [Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom); Applied Computational Biology and Bioinformatics Group, Paterson Institute for Cancer Research, Manchester (United Kingdom); Miller, Crispin J. [Applied Computational Biology and Bioinformatics Group, Paterson Institute for Cancer Research, Manchester (United Kingdom); Davidson, Susan [Christie National Health Service Foundation Trust, Manchester (United Kingdom); Sanjose, Silvia de; Bosch, Xavier [Cancer Epidemiology Research Program, Catalan Institute of Oncology, L' Hospitalet de Llobregat (Spain); Stern, Peter L. [Immunology Group, Paterson Institute for Cancer Research, Manchester (United Kingdom); West, Catharine M.L., E-mail: Catharine.West@manchester.ac.uk [Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom)

    2013-04-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity. Methods and Materials: HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA{sub 25}) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays. Results: Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14). Conclusion: The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.

  16. Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy.

    Science.gov (United States)

    Nagy, Viorica Magdalena; Buiga, R; Brie, Ioana; Todor, N; Tudoran, Oana; Ordeanu, Claudia; Virág, Piroska; Tarta, Oana; Rus, Meda; Bălăcescu, O

    2011-01-01

    Despite the improvement in the treatment results due to modern irradiation techniques and to the association of chemo-radiotherapy, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Efforts to implement new therapeutic strategies in order to obtain better results in patients with cervical cancer appear justified. Neovascularization is an important step in the tumor progression and the therapeutic targeting of the tumor blood vessels appears to be a good strategy to follow in the anti-cancer treatment. Thus, even in an incipient phase of the clinical research process, the combination between the anti-angiogenic aimed therapies and the current radio-chemotherapy seems to represent a new, feasible and promising approach. The aim of the present study was to determine the prognostic and/or predictive value of some biological markers of tumor angiogenesis and of their implication in increasing the efficacy of current treatments for this cancer. So far, 54 women were included in a prospective trial: 44 having an advanced cervical carcinoma and 10 healthy women, as controls. A tumor biopsy and a blood sample were obtained from each patient before the start of therapy. The density of microvascularization was assessed using CD34 monoclonal antibody (hot spot technique), the expression of angiogenic factors VEGFR, EGFR and COX-2 were determined in tumor biopsies by specific immunohistochemistry techniques, using primary antibodies anti-EGFR, anti-VEGF and anti-COX-2 respectively. The quantitative polymerase chain reaction (Real Time PCR) was employed for assessing the expression level of the genes involved. Serum VEGF was determined by quantitative ELISA technique. Among the studied clinical and molecular factors, we found to be predictive for the type of response the following factors: tumor size at diagnosis (p=0.01), VEGFR2 expression (p=0.02) and a tendency to significance for patients

  17. Increase in the fraction of necrotic, not apoptotic, cells in SiHa xenograft tumours shortly after irradiation

    International Nuclear Information System (INIS)

    Olive, P.L.; Vikse, C.M.; Vanderbyl, S.

    1999-01-01

    Background and purpose: Approximately 18% of the cells recovered by rapid mechanical dissociation of SiHa xenograft tumours contain large numbers of DNA strand breaks. The number of damaged cells increases to 30-40% 4-6 h after exposure to 5 or 15 Gy, returning to normal levels by 12 h. This observation is reminiscent of the rate of production of apoptotic cells in other murine and human xenograft tumours. The nature of this damage, rate of development and relation to cell proliferation rate were therefore examined in detail.Materials and methods: SiHa human cervical carcinoma cells were grown as xenograft tumours in SCID mice. Single-cell suspensions were prepared as a function of time after irradiation of the mouse and examined for DNA damage using the alkaline comet assay. Cell cycle progression was measured by flow cytometry evaluation of anti-bromodeoxyuridine-labelled tumour cells.Results: Significant numbers of apoptotic cells could not be detected in irradiated SiHa tumours using an end-labelling assay, electron microscopy, or histological examination of thin sections. Instead, xenograft cells exhibiting extensive DNA damage in the comet assay were predominantly necrotic cells. The increase in the proportion of heavily damaged cells 4-6 h after irradiation could be the result of an interplay between several factors including loss of viable cells and change in production or loss of necrotic cells. Analysis of the progression of BrdUrd-labelled cells confirmed that while 35% of cells from untreated SiHa tumours had divided and entered G 1 phase by 6 h after BrdUrd injection, none of the labelled cells from tumours exposed to 5 or 15 Gy had progressed to G 1 .Conclusions: The increase in the percentage of SiHa tumour cells with extensive DNA damage 4-6 h after irradiation is attributable to necrosis, not apoptosis. Cell cycle progression and cell loss are likely to influence the kinetics of appearance of both apoptotic and necrotic cells in irradiated tumours

  18. Prevalence of cervical intraepithelial neoplasia and invasive carcinoma based on cytological screening in the region of Campinas, São Paulo, Brazil Prevalência da neoplasia intra-epitelial cervical e do carcinoma invasivo com base no rastreamento citológico na região de Campinas, São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Maria Gabriela L. d'Ottaviano-Morelli

    2004-02-01

    Full Text Available This study aimed to estimate and analyze the prevalence of cervical intraepithelial neoplasia (CIN and invasive cervical carcinoma based on cytological diagnosis. The study included 120,635 women undergoing cytological exams in public health services in the region of Campinas, São Paulo State, Brazil, between September 1998 and March 1999. Prevalence rates per 100,000 women were: 354 for CIN I; 255 for CIN II; 141 for CIN III; and 24 for invasive carcinoma. As age increased, prevalence rates and prevalence ratios decreased for CIN grades I and II and increased for CIN III until the 50-54 age group, decreasing thereafter The prevalence rate of invasive carcinoma increased with age. The prevalence pattern of CIN II was distinct from that of CIN III, but similar to that of CIN I. This would not have been observed if the Bethesda System had been used for cytological diagnosis. Mean age at time of CIN II diagnosis was about 10 years less than for CIN III diagnosis. Therefore, a high-grade lesion diagnosed in a young woman according to the Bethesda System would probably be a CIN II, whereas in an older woman it would probably be a CIN III.O objetivo deste estudo foi estimar e analisar a prevalência das neoplasias intra-epiteliais cervicais (NIC e do carcinoma invasivo do colo uterino, com base no diagnóstico citológico. Foram incluídas 120.635 mulheres que realizaram o exame citológico, entre setembro de 1998 a março de 1999, nos serviços públicos de saúde da região de Campinas, Brasil. As prevalências por 100 mil mulheres foram: 354 para NIC I; 255 para NIC II; 141 para NIC III e 24 de carcinoma invasivo. À medida que a idade aumentou, as prevalências e razões de prevalência diminuíram para NIC I e NIC II, e aumentaram para NIC III até 50-54 anos, decrescendo após. A prevalência do carcinoma invasivo aumentou com a idade. O padrão da prevalência da NIC II é distinto do padrão da NIC III e semelhante ao da NIC I, o que n

  19. Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program.

    Science.gov (United States)

    Maggino, Tiziano; Sciarrone, Rocco; Murer, Bruno; Dei Rossi, Maria Rosa; Fedato, Chiara; Maran, Michela; Lorio, Melania; Soldà, Marika; Zago, Fiorella; Giorgi Rossi, Paolo; Zorzi, Manuel

    2016-08-23

    HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy. From October 2011 to May 2014, women aged 25-64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects. Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8%; relative rate (RR) 1.11, 95% confidence interval (CI) 1.05-1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6%; RR 2.02, 95% CI 1.82-2.25) but similar to the HPV DNA programs (4.8%; RR 1.02; 95% CI 0.96-1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19-1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40-1.16). The overall RR was 1.29 (95% CI 1.05-1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰; RR 2.50, 95% CI 1.76-3.62). A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.

  20. Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma

    International Nuclear Information System (INIS)

    Rao, Pulivarthi H; Murty, Vundavalli VVS; Arias-Pulido, Hugo; Lu, Xin-Yan; Harris, Charles P; Vargas, Hernan; Zhang, Fang F; Narayan, Gopeshwar; Schneider, Achim; Terry, Mary Beth

    2004-01-01

    Carcinoma of uterine cervix is the second most common cancers among women worldwide. Combined radiation and chemotherapy is the choice of treatment for advanced stages of the disease. The prognosis is poor, with a five-year survival rate ranging from about 20–65%, depending on stage of the disease. Therefore, genetic characterization is essential for understanding the biology and clinical heterogeneity in cervical cancer (CC). We used a genome-wide screening method – comparative genomic hybridization (CGH) to identify DNA copy number changes in 77 patients with cervical cancer. We applied categorical and survival analyses to analyze whether chromosomal changes were related to clinico-pathologic characteristics and patients survival. The CGH analysis revealed a loss of 2q33-q37 (57.1%), gain of 3q (54.5%) and chromosomal amplifications (20.77%) as frequent genetic changes. A total of 15 amplified chromosomal sites were detected in 16 cases that include 1p31, 2q32, 7q22, 8q21.2-q24, 9p22, 10q21, 10q24, 11q13, 11q21, 12q15, 14q12, 17p11.2, 17q22, 18p11.2, and 19q13.1. Recurrent amplified sites were noted at 11q13, 11q21, and 19q13.1. The genomic alterations were further evaluated for prognostic significance in CC patients, and we did not find any correlation with a number of clinical or histological parameters. The tumors harboring HPV18 exhibited higher genomic instability compared to tumors with HPV 16. This study demonstrated that 2q33-q37 deletions, 3q gains and chromosomal amplifications as characteristic changes in invasive CC. These genetic alterations will aid in the identification of novel tumor suppressor gene(s) at 2q33-q37 and oncogenes at amplified chromosomal sites. Molecular characterization of these chromosomal changes utilizing the current genomic technologies will provide new insights into the biology and clinical behavior of CC

  1. Comparison between CT and histopathological findings of cervical lymph node metastases in the oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Uchida, Akemi

    2001-01-01

    The purpose of this study is to clarify the relationship between the findings of contrast-enhanced CT scans and the histopathological findings of regional lymph nodes obtained from a complete extirpation of oral squamous cell carcinoma. Twenty-seven pairs of contrast-enhanced CT scans and histopathological specimens of 27 oral squamous cell carcinoma used in this study were obtained at Kyushu Dental College Hospital between 1987 and 1999. The primary site of the 27 tumor consists of the tongue (13 cases), the mandibular gingiva (6 cases), the maxillary gingiva (4 cases), the floor of the oral cavity (3 cases), and the buccal mucosa (1 case). The results obtained were as follows: Of the 27 cases, 11 (41%) were proven to be positive lymph nodes metastatic cases histopathologically. Metastatic lymph nodes were predominantly detected in both the submandibular regions and the superior internal jugular chains (95%). The length and the ratio of the short and long axes of the metastatic lymph nodes were larger than those of the non-metastatic lymph nodes. Many of the metastatic lymph nodes revealed a low density in their central area and were also accompanied by a thin ring enhancement. Non-metastatic lymph nodes, affected by inflammation, often revealed a heterogeneous density. The ring enhancement was predominantly seen in the metastatic lymph nodes (45%), which were filled with a well-differentiated tumor cell. In the metastatic lymph nodes, which were filled with moderately-differentiated tumor cells, were seen heterogeneous density, but a ring enhancement was not seen. In the metastatic lymph nodes, it was difficult to decide the metastasis by contrast CT scan, if the tumor extension degree was not predominant. The ring enhancement was caused by the dilatation of the capsular vessels, but not by the extra capsular spread of the tumor cells. (author)

  2. Photo-triggered destabilization of nanoscopic vehicles by dihydroindolizine for enhanced anticancer drug delivery in cervical carcinoma.

    Science.gov (United States)

    Singh, Priya; Choudhury, Susobhan; Kulanthaivel, Senthilguru; Bagchi, Damayanti; Banerjee, Indranil; Ahmed, Saleh A; Pal, Samir Kumar

    2018-02-01

    The efficacy and toxicity of drugs depend not only on their potency but also on their ability to reach the target sites in preference to non-target sites. In this regards destabilization of delivery vehicles induced by light can be an effective strategy for enhancing drug delivery with spatial and temporal control. Herein we demonstrate that the photoinduced isomerization from closed (hydrophobic) to open isomeric form (hydrophilic) of a novel DHI encapsulated in liposome leads to potential light-controlled drug delivery vehicles. We have used steady state and picosecond resolved dynamics of a drug 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor the efficacy of destabilization of liposome in absence and presence UVA irradiation. Steady state and picosecond resolved polarization gated spectroscopy including the well-known strategy of solvation dynamics and Förster resonance energy transfer; reveal the possible mechanism out of various phenomena involved in destabilization of liposome. We have also investigated the therapeutic efficacy of doxorubicin (DOX) delivery from liposome to cervical cancer cell line HeLa. The FACS, confocal fluorescence microscopic and MTT assay studies reveal an enhanced cellular uptake of DOX leading to significant reduction in cell viability (∼40%) of HeLa followed by photoresponsive destabilization of liposome. Our studies successfully demonstrate that these DHI encapsulated liposomes have potential application as a smart photosensitive drug delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Variability in target delineation of cervical carcinoma: A Korean radiation oncology group study (KROG 15-06)

    Science.gov (United States)

    Joo, Ji Hyeon; Cho, Byung Chul; Jeong, Chi Young; Park, Won; Kim, Hak Jae; Yoon, Won Sup; Yoon, Mee Sun; Kim, Ji-Yoon; Choi, Jin Hwa; Choi, Youngmin; Kim, Joo-Young

    2017-01-01

    Purpose To determine inter-observer variability in target volume definition of cervical cancer in radical and adjuvant radiotherapy (RT) settings. Methods Eight physicians contoured CTVs of 2 patients underwent definitive and postoperative RT. Each volume was analyzed using the individual/median volume ratio and generalized conformity index (CIgen). And center of mass (COM) of each contour was calculated. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). Results For definitive RT, the individual/median volume ratio ranged from 0.51 to 1.41, and CIgen was 0.531. Mean 3-dimensional distances of average to each COM were 7.8 mm. For postoperative RT setting, corresponding values were 0.65–1.38, 0.563, and 5.3 mm. Kappa value of expert agreement was 0.65 and 0.67, respectively. STAPLE estimates of the sensitivity, specificity, and kappa measures of inter-physician agreement were 0.73, 0.98, and 0.65 for the definitive and 0.75, 0.98, and 0.67 for the adjuvant radiotherapy setting. The largest difference was observed in the superior-inferior direction, particularly in the upper vagina and the common iliac area. Conclusion As there was still some variability in target delineation, more detailed guidelines for target volume delineation and continuing education would help to reduce this uncertainty. PMID:28301492

  4. Role of ultrasound in the assessment of percutaneous laser ablation of cervical metastatic lymph nodes from thyroid carcinoma.

    Science.gov (United States)

    Zhang, Lu; Zhou, Wei; Zhan, WeiWei

    2018-04-01

    Background Few studies have examined the feasibility and efficiency of performing ultrasound and contrast-enhanced ultrasound (CEUS) after percutaneous laser ablation (PLA) of cervical metastatic lymph nodes from thyroid cancer. Purpose To investigate and describe the use of conventional ultrasound and CEUS in evaluating PLA of metastatic lymph nodes. Material and Methods PLA was performed in a small, prospective, observational study of 21 metastatic lymph nodes in 17 thyroid cancer patients who underwent radical thyroid resection. CEUS was conducted prior to PLA and 1 h and seven days after ablation. Conventional ultrasound examination of all nodes was performed during follow-up after ablation. We observed contrast agent perfusion in the lymph nodes, calculated perfusion defect volumes using CEUS and determined the rates of reduction for metastatic lymph nodes for a mean duration of 17.86 ± 4.704 months (range = 12-27 months). Results CEUS demonstrated that the perfusion defect volume was larger on day 7 than on day 1 post-ablation in 47% of the ablated nodes. Compared to the largest diameters and volumes pre-PLA, the corresponding post-PLA values significantly decreased ( P  0.05 versus baseline). Conclusion CEUS can be effectively used to distinguish the margins of ablated regions, assess the accuracy of PLA, and monitor short-term changes in necrotic areas. However, long-term follow-up assessments of the curative effect of PLA will predominantly rely on conventional ultrasonography.

  5. Radio(chemo)therapy in the management of squamous cell carcinoma of cervical lymph nodes from an unknown primary site. A retrospective analysis

    International Nuclear Information System (INIS)

    Fakhrian, K.; Thamm, R.; Knapp, S.; Molls, M.; Pigorsch, S.; Geinitz, H.; Haller, B.

    2012-01-01

    The goal was to retrospectively review the outcome of patients with cervical lymph node metastases of squamuos cell carcinoma of unknown primary site (CUP) treated with radio(chemo)therapy. Patients and methods A total of 65 patients with CUP N1-3, M0, treated between 1988 and 2009 were evaluated: 61 patients underwent surgical resection followed by postoperative radio(chemo)therapy, 4 patients received definitive radiochemotherapy. Radiotherapy of bilateral neck nodes + the parapharyngeal region (COMP-RT) was performed in 48 patients (80%) and a unilateral radiotherapy of lymph nodes (UL-RT) in 17 patients (20%). Results After a median follow-up time of 64 months (range 3-219 months), the estimated 2- and 5-year overall survival (OS) rates were 71 ± 6% and 48 ± 7%, respectively. The recurrent free survival (RFS) rate at 2- and 5-years was 58 ± 6% and 48% ± 7%, respectively. Extracapsular spread, resection status (R0 vs. R1/R2), neck lymph node level (I-III vs. IV-V), and Karnofsky index (60-70 vs. 80-100) were significant prognostic factors for OS and RFS in the univariate analysis. Lower nodal stage (N1/N2a vs. N2b/N2c/N3) was significantly associated with a better OS. Resection status and involvement of lymph node level IV significantly affected the OS and RFS in the multivariate analysis. COMP-RT or concurrent chemotherapy was not associated with a better OS or RFS. Conclusion An advantage of comprehensive radiotherapy or radiochemotherapy compared with unilateral radiotherapy of lymph nodes was not observed. (orig.)

  6. A Clinical Decision Support System Using Ultrasound Textures and Radiologic Features to Distinguish Metastasis From Tumor-Free Cervical Lymph Nodes in Patients With Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Abbasian Ardakani, Ali; Reiazi, Reza; Mohammadi, Afshin

    2018-03-30

    This study investigated the potential of a clinical decision support approach for the classification of metastatic and tumor-free cervical lymph nodes (LNs) in papillary thyroid carcinoma on the basis of radiologic and textural analysis through ultrasound (US) imaging. In this research, 170 metastatic and 170 tumor-free LNs were examined by the proposed clinical decision support method. To discover the difference between the groups, US imaging was used for the extraction of radiologic and textural features. The radiologic features in the B-mode scans included the echogenicity, margin, shape, and presence of microcalcification. To extract the textural features, a wavelet transform was applied. A support vector machine classifier was used to classify the LNs. In the training set data, a combination of radiologic and textural features represented the best performance with sensitivity, specificity, accuracy, and area under the curve (AUC) values of 97.14%, 98.57%, 97.86%, and 0.994, respectively, whereas the classification based on radiologic and textural features alone yielded lower performance, with AUCs of 0.964 and 0.922. On testing the data set, the proposed model could classify the tumor-free and metastatic LNs with an AUC of 0.952, which corresponded to sensitivity, specificity, and accuracy of 93.33%, 96.66%, and 95.00%. The clinical decision support method based on textural and radiologic features has the potential to characterize LNs via 2-dimensional US. Therefore, it can be used as a supplementary technique in daily clinical practice to improve radiologists' understanding of conventional US imaging for characterizing LNs. © 2018 by the American Institute of Ultrasound in Medicine.

  7. Radio(chemo)therapy in the management of squamous cell carcinoma of cervical lymph nodes from an unknown primary site. A retrospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Fakhrian, K.; Thamm, R.; Knapp, S.; Molls, M.; Pigorsch, S.; Geinitz, H. [Technische Univ. Muenchen (Germany). Dept. of Radiation Oncology; Haller, B. [Technische Univ. Muenchen (Germany). Inst. of Medical Statistics and Epidemiology

    2012-01-15

    The goal was to retrospectively review the outcome of patients with cervical lymph node metastases of squamuos cell carcinoma of unknown primary site (CUP) treated with radio(chemo)therapy. Patients and methods A total of 65 patients with CUP N1-3, M0, treated between 1988 and 2009 were evaluated: 61 patients underwent surgical resection followed by postoperative radio(chemo)therapy, 4 patients received definitive radiochemotherapy. Radiotherapy of bilateral neck nodes + the parapharyngeal region (COMP-RT) was performed in 48 patients (80%) and a unilateral radiotherapy of lymph nodes (UL-RT) in 17 patients (20%). Results After a median follow-up time of 64 months (range 3-219 months), the estimated 2- and 5-year overall survival (OS) rates were 71 {+-} 6% and 48 {+-} 7%, respectively. The recurrent free survival (RFS) rate at 2- and 5-years was 58 {+-} 6% and 48% {+-} 7%, respectively. Extracapsular spread, resection status (R0 vs. R1/R2), neck lymph node level (I-III vs. IV-V), and Karnofsky index (60-70 vs. 80-100) were significant prognostic factors for OS and RFS in the univariate analysis. Lower nodal stage (N1/N2a vs. N2b/N2c/N3) was significantly associated with a better OS. Resection status and involvement of lymph node level IV significantly affected the OS and RFS in the multivariate analysis. COMP-RT or concurrent chemotherapy was not associated with a better OS or RFS. Conclusion An advantage of comprehensive radiotherapy or radiochemotherapy compared with unilateral radiotherapy of lymph nodes was not observed. (orig.)

  8. Cervical Cap

    Science.gov (United States)

    ... giving birth vaginally, which means the cervical cap may not fit as well. Inconsistent or incorrect use of the cervical cap increases your risk of pregnancy. For example, you may get pregnant when using the cervical cap if: ...

  9. Sensory and motor dysfunction assessed by anorectal manometry in uterine cervical carcinoma patients with radiation-induced late rectal complication

    International Nuclear Information System (INIS)

    Kim, Gwi Eon; Lim, John Jihoon; Park, Won; Park, Hee Chul; Chung, Eun Ji; Seong, Jinsil; Suh, Chang Ok; Lee, Yong Chan; Park, Hyo Jin

    1998-01-01

    Purpose: To investigate the effects of radiation on anorectal function in patients with carcinoma of the uterine cervix. Methods and Materials: Anorectal manometry was carried out on 24 patients (complication group) with late radiation proctitis. All of the manometric data from these patients were compared with those from 24 age-matched female volunteers (control group), in whom radiation treatment had not yet been performed. Results: Regardless of the severity of proctitis symptoms, 25% of patients demonstrated all their manometric data within the normal range, but 75% of patients exhibited one or more abnormal manometric parameters for sensory or motor functions. Six patients (25%) had an isolated sensory dysfunction, eight patients (33.3%) had an isolated motor dysfunction, and four patients (16.7%) had combined disturbances of both sensory and motor functions. The maximum tolerable volume, the minimal threshold volume, and the urgent volume in the complication group were significantly reduced compared with those in the control group. The mean squeeze pressure in the complication group was significantly reduced, whereas the mean resting pressure and anal sphincter length were unchanged. Conclusions: Physiologic changes of the anorectum in patients with late radiation proctitis seem to be caused by a variety of sensory and/or motor dysfunctions in which many different mechanisms are working together. The reduced rectal reservoir capacity and impaired sensory functions were crucial factors for functional disorder in such patients. In addition, radiation damage to the external anal sphincter muscle was considered to be an important cause of motor dysfunction

  10. Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-07-30

    The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented. The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic aresenal for this patient population, in terms of survival, local control, and complications. Overall survival, 85% at 2 years and local control, 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%), and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12) Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs 45% at 2 years (p = 0.03). The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. 33 refs., 3 figs., 5 tabs.

  11. The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes

    Science.gov (United States)

    Piroozmand, Ahmad; Mostafavi Zadeh, Seyed Mostafa; Madani, Azita; Soleimani, Reza; Nedaeinia, Reza; Niakan, Mohammad; Avan, Amir; Manian, Mostafa; Moradi, Mohammad; Eftekhar, Zahra

    2016-01-01

    Background Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. Objectives The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. Materials and Methods Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. Results The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. Conclusions Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID:27279992

  12. MRI-assisted versus conventional treatment planning in brachytherapy of cervical and endometrial carcinoma: The impact of individual anatomy on dose distribution in target volume and organs at risk

    International Nuclear Information System (INIS)

    Wulf, Joern; Sauer, Otto A.; Herbolsheimer, Michael; Oppitz, Ulrich; Flentje, Michael

    1996-01-01

    Objective: Dose prescription and definition of target volume in brachytherapy of cervical and endometrial cancer are calculated to standard points as Manchester point A or point My(ometrium) in most centers. Calculation of doses to organs at risk mainly relies on ICRU-report 38. But standard dose prescription neglects individual patient anatomy. While MRI and CT had widespread impact on individual planning in external beam radiotherapy, there is still a minor influence on brachytherapy. The impact of individual anatomy on dose distribution in target volume and organs at risk demonstrates the objective of individual brachytherapy planning. Materials and Methods: 8 patients with cervical and 4 patients with endometrial carcinoma underwent MRI of the pelvis with in-situ applicators (ring-tandem applicators for cervical carcinoma and modified Heyman-capsules for endometrial carcinoma). T1w slices were angulated coronal and sagittal to get rectangular reproductions to applicator axis. Orthogonal or isocentric X-ray films for conventional treatment planning were done. MRI-information on target and organs at risk was transformed into coordinates relative to applicator axis and dose calculation on the database of conventional treatment planning was performed by Nucletron Planning System PLATO. Isodoses were projected into MRI slices. Prescribed dose to patients with cervical cancer was 8.5 Gy to point A resp. 10 Gy to point My (2cm below fundal myometrium and 2cm lateral applicator axis) in endometrial cancer. Results: Dose prescription to Manchester point A or point My represented in only 50% of cases uterine serosa. Instead of 2cm lateral of applicator axis, uterine surface ranged from 1.0 cm to 3.9 cm at the level of point A (mean 2.25 cm coronal and 1.77 cm sagittal) and from 1.5 cm to 4.4 cm at the level of point My (mean 2.7 cm coronal and 2.1 cm sagittal). Uterine volume ranged from 69 cc to 277 cc, mean volume was 150cc. Dose-volume histograms of patients with

  13. Early effects of treatment with radium and cobalt-60 gamma radiation on the proportions and absolute counts of T and B lymphocytes in peripheral blood of women with cervical carcinoma

    International Nuclear Information System (INIS)

    Pluzanska, A.; Robak, T.; Kuchowicz, W.; Bartuzel, T.; Studencki, E.; Zadrozna, O.; Mazurowa, A.

    1977-01-01

    In 20 women with cervical carcinoma the T and B lymphocyte counts were determined in peripheral blood. The determinations were carried out before starting treatment and immediately after radium therapy in a mean dose of 6573 mgh and then after full therapeutic dose of cobalt-60 radiation of 4000 R. For identification of T lymphocytes the rosette E test was used and lymphocytes B were identified by means of the EAC rosette test. Presence of immunoglobulins on lymphocytes B was determined as well. In women with cervical carcinoma the total lymphocyte count in 1 mm 3 of blood, the proportions and absolute counts of T and B lymphocytes were not different from those in healthy women. Immediately after radium therapy the lymphocyte count in peripheral blood fell which was due mainly to a fall of the total count and in the proportion of B lymphocytes. The proportion of lymphocytes T was unchanged and their quantitative fall was statistically not significant. After application of the total therapeutic dose of cobalt-60 radiation a further fall of lymphocyte count was observed, due to a fall of the absolute count of T and B lymphocytes. Their proportions were unchanged. (author)

  14. Proteasome Inhibition Contributed to the Cytotoxicity of Arenobufagin after Its Binding with Na, K-ATPase in Human Cervical Carcinoma HeLa Cells.

    Science.gov (United States)

    Yue, Qingxi; Zhen, Hong; Huang, Ming; Zheng, Xi; Feng, Lixing; Jiang, Baohong; Yang, Min; Wu, Wanying; Liu, Xuan; Guo, Dean

    2016-01-01

    Although the possibility of developing cardiac steroids/cardiac glycosides as novel cancer therapeutic agents has been recognized, the mechanism of their anticancer activity is still not clear enough. Toad venom extract containing bufadienolides, which belong to cardiac steroids, has actually long been used as traditional Chinese medicine in clinic for cancer therapy in China. The cytotoxicity of arenobufagin, a bufadienolide isolated from toad venom, on human cervical carcinoma HeLa cells was checked. And, the protein expression profile of control HeLa cells and HeLa cells treated with arenobufagin for 48 h was analyzed using two-dimensional electrophoresis, respectively. Differently expressed proteins in HeLa cells treated with arenobufagin were identified and the pathways related to these proteins were mapped from KEGG database. Computational molecular docking was performed to verify the binding of arenobufagin and Na, K-ATPase. The effects of arenobufagin on Na, K-ATPase activity and proteasome activity of HeLa cells were checked. The protein-protein interaction network between Na, K-ATPase and proteasome was constructed and the expression of possible intermediate proteins ataxin-1 and translationally-controlled tumor protein in HeLa cells treated with arenobufagin was then checked. Arenobufagin induced apoptosis and G2/M cell cycle arrest in HeLa cells. The cytotoxic effect of arenobufagin was associated with 25 differently expressed proteins including proteasome-related proteins, calcium ion binding-related proteins, oxidative stress-related proteins, metabolism-related enzymes and others. The results of computational molecular docking revealed that arenobufagin was bound in the cavity formed by the transmembrane alpha subunits of Na, K-ATPase, which blocked the pathway of extracellular Na+/K+ cation exchange and inhibited the function of ion exchange. Arenobufagin inhibited the activity of Na, K-ATPase and proteasome, decreased the expression of Na, K

  15. Proteasome Inhibition Contributed to the Cytotoxicity of Arenobufagin after Its Binding with Na, K-ATPase in Human Cervical Carcinoma HeLa Cells.

    Directory of Open Access Journals (Sweden)

    Qingxi Yue

    Full Text Available Although the possibility of developing cardiac steroids/cardiac glycosides as novel cancer therapeutic agents has been recognized, the mechanism of their anticancer activity is still not clear enough. Toad venom extract containing bufadienolides, which belong to cardiac steroids, has actually long been used as traditional Chinese medicine in clinic for cancer therapy in China. The cytotoxicity of arenobufagin, a bufadienolide isolated from toad venom, on human cervical carcinoma HeLa cells was checked. And, the protein expression profile of control HeLa cells and HeLa cells treated with arenobufagin for 48 h was analyzed using two-dimensional electrophoresis, respectively. Differently expressed proteins in HeLa cells treated with arenobufagin were identified and the pathways related to these proteins were mapped from KEGG database. Computational molecular docking was performed to verify the binding of arenobufagin and Na, K-ATPase. The effects of arenobufagin on Na, K-ATPase activity and proteasome activity of HeLa cells were checked. The protein-protein interaction network between Na, K-ATPase and proteasome was constructed and the expression of possible intermediate proteins ataxin-1 and translationally-controlled tumor protein in HeLa cells treated with arenobufagin was then checked. Arenobufagin induced apoptosis and G2/M cell cycle arrest in HeLa cells. The cytotoxic effect of arenobufagin was associated with 25 differently expressed proteins including proteasome-related proteins, calcium ion binding-related proteins, oxidative stress-related proteins, metabolism-related enzymes and others. The results of computational molecular docking revealed that arenobufagin was bound in the cavity formed by the transmembrane alpha subunits of Na, K-ATPase, which blocked the pathway of extracellular Na+/K+ cation exchange and inhibited the function of ion exchange. Arenobufagin inhibited the activity of Na, K-ATPase and proteasome, decreased the

  16. Metástasis cervical contralateral en el carcinoma epidermoide de la cavidad oral: Estudio clínico analítico retrospectivo en 315 pacientes primariamente tratados con cirugía Contralateral neck metastasis in squamous cell carcinoma of the oral cavity: An analytical retrospective clinical study of 315 patients primarily treated with surgery

    Directory of Open Access Journals (Sweden)

    R. González-García

    2008-06-01

    Full Text Available Objetivos. Existen en la literatura numerosos estudios en relación con los factores pronósticos implicados en la aparición de metástasis cervicales ipsilaterales en el carcinoma epidermoide de cavidad oral. Sin embargo, no existen estudios clínicos amplios acerca de la asociación de factores clínico-patológicos y la aparición de metástasis cervicales contralaterales tras la resección quirúrgica del tumor primario. El propósito de este estudio es el análisis de los factores implicados en la aparición de metástasis cervical contralateral en pacientes con carcinoma epidermoide de cavidad oral primariamente tratados con cirugía. Pacientes y métodos. Se analizó una serie de 315 pacientes consecutivos con carcinoma epidermoide de la cavidad oral no tratados previamente. Se realizó un estudio complementario del subgrupo de 203 pacientes con carcinoma epidermoide del borde lateral de la lengua libre, por tratarse de un grupo muy prevalente en la serie analizada. Todos los pacientes recibieron tratamiento quirúrgico con o sin tratamiento radioterápico adyuvante. Varias fueron las variables clínicas e histopatológicas analizadas, como son: las características clínicas del tumor, el estadio tumoral, el grado de diferenciación histológica, el tipo de disección cervical, la supervivencia enfermedad- específica, los márgenes quirúrgicos en la pieza resecada, la extensión ganglionar extracapsular, la diseminación perineural y la afectación ósea. Resultados. La duración media del seguimiento de los pacientes que sobrevivieron fue de 70,9 ± 49,6 meses. Ochenta y tres pacientes murieron a causa de la enfermedad a lo largo del seguimiento. Cuarenta y siete de estos pertenecían al subgrupo de pacientes con carcinoma epidermoide de lengua. Un total de 147 pacientes permanecía vivo sin evidencias de recurrencia de la enfermedad al final del periodo de seguimiento, 116 de los cuales correspondían al subgrupo de pacientes con

  17. Carcinoma do colo do útero: taxa de sobrevida e fatores prognósticos em mulheres no Estado de Mato Grosso Carcinoma de cuello de útero: tasa de sobrevida y factores pronósticos en mujeres en el Estado de Mato Grosso Cervical carcinoma: survival rate and prognostic factors in women in the state of Mato Grosso

    Directory of Open Access Journals (Sweden)

    Janete Tomiyoshi Nakagawa

    2011-01-01

    Full Text Available OBJETIVOS: Analisar a taxa de sobrevida de mulheres submetidas ao tratamento de câncer do colo do útero no Estado de Mato Grosso e identificar os fatores prognósticos que mais influenciaram no tempo de sobrevida. MÉTODOS: Estudo tipo coorte, realizado por meio daanálise dos prontuários clínicos, e dados do Sistema de Informação do Colo do Útero, Sistema de Informação sobre Mortalidade, Sistema de Informação Autorização de Procedimentos Alta Complexidade. A população correspondeu a 55 mulheres que apresentaram esse tipo de carcinoma e tiveram seguimento clínico entre 2002 e 2007. RESULTADOS: A taxa de sobrevida global foi de 66,7%. Os fatores prognósticos que influenciaram na taxa de sobrevida foram: idade, presença de sintomatologia sugestiva de câncer cervical e estágio tardio da doença no momento do diagnóstico. CONCLUSÃO: Apesar da taxa de sobrevida global encontrada assemelhar-se às taxas de países desenvolvidos, foi menor em mulheres com condições sociais desfavoráveis.OBJETIVOS: Analizar la tasa de sobrevida de mujeres sometidas al tratamiento de cáncer de cuello de útero en el Estado de Mato Grosso e identificar los factores pronósticos que más influyeron en el tiempo de sobrevida. MÉTODOS: Estudio de tipo cohorte, realizado por medio del análisis de las historias clínicas, entre otros. La población correspondió a 55 mujeres que presentaron ese tipo de carcinoma y tuvieron seguimiento clínico entre 2002 y 2007. RESULTADOS: La tasa de sobrevida global fue del 66,7%. Los fatores pronósticos que influyeron en la tasa de sobrevida fueron: edad, presencia de sintomatología sugestiva de cáncer cervical y estadío tardío de la enfermedad en el momento del diagnóstico. CONCLUSIÓN: A pesar de que la tasa de sobrevida global encontrada se asemeje a las tasas de países desarrollados, fue menor en mujeres con condiciones sociales desfavorables.OBJECTIVES: To analyze the survival rate of women undergoing

  18. Radiobiological hypoxic fraction does not correlate with pO2 measurements in eight human tumor xenografts into nude mice

    International Nuclear Information System (INIS)

    Taghian, A.; Huang, P.; Griffon, G.; Hartford, A.; Allam, A.; Costa, A. da; Kozin, S.; Suit, H.D.

    1997-01-01

    Purpose/Objective: Clinical and laboratory reports suggest that hypoxia limits local control probability in tumors treated by radiation. Significant increase in the TCD 50 (the dose of radiation needed to control 50% of the tumors) was obtained in a number of tumor models when the tumors were rendered hypoxic by clamping. Furthermore, recent data have shown the value of measuring the pO2 using electrodes in predicting the tumor response to radiation in cervical cancer. The aim of this study is to investigate the correlation between the radiobiological hypoxic fraction (HF) and the pO2 measurements of human tumor xenografts. Materials and Methods: Eight human tumor xenografts (five glioblastoma, one squamous cell carcinoma, one colon cancer, and one soft tissue sarcoma) were used in these experiments. Tumor chunks 2 mm in diameter were implanted into the hindleg of 5 Gy whole-body irradiated nude mice. When the tumor size reached 110 mm 3 , radiation was administered in a single dose ranging from 17.5 Gy to 90 Gy in hypoxic conditions. Acute hypoxia was induced by clamping the tumor bearing leg three minutes before and during the treatment. When aerobic conditions were required, the tumor bearing leg was immobilized by a hook which fitted around the ankle. Seven to 10 tumors were assigned to each dose level in each assay; there were 6 to 8 dose levels per assay. Starting at 2-3 weeks after irradiation, the animals were examined once per week and scored for presence of local tumor; if present, tumor diameters were measured. Tumor response is described in terms of radiation dose (in Gy) required to control 50% of the xenografts (TCD 50 ). The (HF) was determined using the formula of Howes (HF=e - ((TCD 50 hypoxic-TCD 50 air)(Do hypoxic)) and assuming an oxygen enhancement ratio of 3.0: (D o hyp=D o air x 3.0) (the D o air was separately determined in vitro for the corresponding cell lines). The pO2 measurements used electrodes as published (Boucher et al

  19. Cervical cancer and pregnancy: treatment management

    International Nuclear Information System (INIS)

    Lazar, I.; Toth, R.

    2011-01-01

    Pregnancy and cervical carcinoma occurring concomitantly causes therapeutic and ethical dilemmas. The management for this situation will depend on the gestational age at the time of diagnosis, disease staging, size of the lesion and the patient’s wish to maintain pregnancy and fertility. Review of the literature suggest that pregnancy does not seem to influence the prognosis of cervical cancer. (author)

  20. GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers.

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    Full Text Available BACKGROUND: Our previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this study were to determine the potential role of GRIM-19 in rescuing p53 protein and inducing cervical cancer cell apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The protein levels of GRIM-19 and p53 were detected in normal cervical tissues from 45 patients who underwent hysterectomy for reasons other than neoplasias of either the cervix or endometrium, and cervical cancer tissues from 60 patients with non-metastatic squamous epithelial carcinomas. Coimmunoprecipitation and GST pull-down assay were performed to examine the interaction of GRIM-19 with 18E6 and E6AP in vivo and in vitro respectively. The competition of 18E6 with E6AP in binding GRIM-19 by performing competition pull-down assays was designed to examine the disruption of E6/E6AP complex by GRIM-19. The augment of E6AP ubiquitination by GRIM-19 was detected in vivo and in vitro ubiquitination assay. The effects of GRIM-19-dependent p53 accumulation on cell proliferation, cell cycle, apoptosis were explored by MTT, flow cytometry and transmission electron microscopy respectively. The tumor suppression was detected by xenograft mouse model. CONCLUSION/SIGNIFICANCE: The levels of GRIM-19 and p53 were concurrently down regulated in cervical cancers. The restoration of GRIM-19 can induce ubiquitination and degradation of E6AP, and disrupt the E6/E6AP complex through the interaction of N-terminus of GRIM-19 with both E6 and E6AP, which protected p53 from degradation and promoted cell apoptosis. Tumor xenograft studies also revealed the suppression of p53 degradation in presence of GRIM-19. These data

  1. Cervical cancer

    Science.gov (United States)

    ... bleeding between periods, after intercourse, or after menopause Vaginal discharge that does not stop, and may be pale, ... Instructions Hysterectomy - abdominal - discharge Hysterectomy - laparoscopic - ... Images Cervical cancer Cervical neoplasia ...

  2. Cervical Cancer

    Science.gov (United States)

    ... the place where a baby grows during pregnancy. Cervical cancer is caused by a virus called HPV. The ... for a long time, or have HIV infection. Cervical cancer may not cause any symptoms at first. Later, ...

  3. Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2007-03-06

    Did you know that cervical cancer rates differ by race/ethnicity and region? Or that cervical cancer can usually be prevented if precancerous cervical lesions are found by a Pap test and treated? Find out how getting regular Pap tests can save a woman's life.  Created: 3/6/2007 by National Breast and Cervical Cancer Early Detection Program.   Date Released: 4/25/2007.

  4. Cervical Myomas

    Science.gov (United States)

    ... Adnexal Torsion Bartholin Gland Cysts Cervical Myomas Cervical Stenosis Endometriomas of the Vulva Inclusion and Epidermal Cysts of the Vulva Noncancerous Ovarian Growths Polyps of the Cervix Skene Duct Cyst Cervical myomas are smooth, benign tumors in the cervix. A myoma may bleed, ...

  5. Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    Did you know that cervical cancer rates differ by race/ethnicity and region? Or that cervical cancer can usually be prevented if precancerous cervical lesions are found by a Pap test and treated? Find out how getting regular Pap tests can save a woman's life.

  6. A multicenter study to quantify systematic variations and associated uncertainties in source positioning with commonly used HDR afterloaders and ring applicators for the treatment of cervical carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Awunor, O., E-mail: onuora.awunor@stees.nhs.uk [The Medical Physics Department, The James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, England (United Kingdom); Berger, D. [Department of Radiotherapy, General Hospital of Vienna, Vienna A-1090 (Austria); Kirisits, C. [Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Vienna A-1090 (Austria)

    2015-08-15

    Purpose: The reconstruction of radiation source position in the treatment planning system is a key part of the applicator reconstruction process in high dose rate (HDR) brachytherapy treatment of cervical carcinomas. The steep dose gradients, of as much as 12%/mm, associated with typical cervix treatments emphasize the importance of accurate and precise determination of source positions. However, a variety of methodologies with a range in associated measurement uncertainties, of up to ±2.5 mm, are currently employed by various centers to do this. In addition, a recent pilot study by Awunor et al. [“Direct reconstruction and associated uncertainties of {sup 192}Ir source dwell positions in ring applicators using gafchromic film in the treatment planning of HDR brachytherapy cervix patients,” Phys. Med. Biol. 58, 3207–3225 (2013)] reported source positional differences of up to 2.6 mm between ring sets of the same type and geometry. This suggests a need for a comprehensive study to assess and quantify systematic source position variations between commonly used ring applicators and HDR afterloaders across multiple centers. Methods: Eighty-six rings from 20 European brachytherapy centers were audited in the form of a postal audit with each center collecting the data independently. The data were collected by setting up the rings using a bespoke jig and irradiating gafchromic films at predetermined dwell positions using four afterloader types, MicroSelectron, Flexitron, GammaMed, and MultiSource, from three manufacturers, Nucletron, Varian, and Eckert & Ziegler BEBIG. Five different ring types in six sizes (Ø25–Ø35 mm) and two angles (45° and 60°) were used. Coordinates of irradiated positions relative to the ring center were determined and collated, and source position differences quantified by ring type, size, and angle. Results: The mean expanded measurement uncertainty (k = 2) along the direction of source travel was ±1.4 mm. The standard deviation

  7. Low morbidity following 9,000-rad intracavitary endocurietherapy (ECT) using the Kumar cervical applicator and external-beam radiotherapy (EXRT) in the management of carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Kumar, P.P.; Good, R.R.; Scott, J.C.; Jones, E.O.; Lynch, G.; McCaul, G.F.

    1988-01-01

    The Kumar Cervical Applicator minimizes patient discomfort and improves patient mobility while reducing the tendency of the applicator to rotate during the 40 to 50 hours of uterine intracavitary endocurietherapy. Patients with previously untreated invasive carcinoma of the uterine cervix, F.I.G.O. stages IB-IVA, were treated with two Kumar intracavitary endocurietherapy (ECT) applications of 2,500 rad each to point ''A,'' and 4,000 rad external-beam radiotherapy (EXRT) to midplane, for a total dose of 9,000 rad. The major complication rate was 2.7 %, and the local control rate was 85 % (22/26 patients) for stage I and II, and 91 % (10/11 patients) for stage III and IVA. (author)

  8. Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

    Science.gov (United States)

    Sood, S; Patel, F D; Ghosh, S; Arora, A; Dhaliwal, L K; Srinivasan, R

    2015-12-01

    Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  9. Human tumour xenografts established and serially transplanted in mice immunologically deprived by thymectomy, cytosine arabinoside and whole-body irradiation

    International Nuclear Information System (INIS)

    Selby, P.J.; Thomas, J.M.; Peckham, M.J.

    1980-01-01

    Mice immunologically deprived by thymectomy, cytosine arabinoside treatment and whole-body irradiation were used to study the growth of human tumours as xenografts. 10/16 melanoma biopsies, 4/13 ovarian carcinoma biopsies and 3/6 uterine cancer biopsies grew as serially transplantable xenograft lines. The tumour lines were studied through serial passages by histology, histo-chemistry, electron microscopy, chromosome analysis, immune fluorescence, growth rate measurement and mitotic counts. They retained the characteristics of the tumours of origin, with the exception of loss of pigmentation in two melanomas, histological dedifferentiation in the uterine carcinomas, and increased mitotic frequency and growth rate in some melanomas. It was concluded that this type of animal preparation is as useful as alternative methods of immunological deprivation, or as athymic nude mice, for the growth of human tumour xenografts, at least for some experimental purposes. (author)

  10. Human Papilloma Virus 16 E6 RNA Interference Enhances Cisplatin and Death Receptor-Mediated Apoptosis in Human Cervical Carcinoma Cells

    NARCIS (Netherlands)

    Tan, Shinta; Hougardy, Brigitte M. T.; Meersma, Gert J.; Schaap, Bessel; de Vries, Elisabeth G. E.; van der Zee, Ate G. J.; de Jong, Steven

    In cervical cancer, the p53 and retinoblastoma (pRb) tumor suppressor pathways are disrupted by the human papilloma virus (HPV) E6 and E7 oncoproteins, because E6 targets p53 and E7 targets pRb for rapid proteasome-mediated degradation. We have investigated whether E6 suppression with small

  11. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, M. F.; Duk, J. M.; Burger, M. P.; de Bruijn, H. W.; Stolz, E.; Herbrink, P.

    1999-01-01

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  12. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  13. Calcium antagonist radioprotectors do not reduce radiotherapeutic efficacy in three human tumor xenografts

    International Nuclear Information System (INIS)

    Floersheim, G.L.; Racine, C.

    1995-01-01

    One Ewing's sarcoma and 2 colon carcinomas were grown as xenografts in immunosuppressed mice. The mice were treated with diltiazem, nifedipine, nimodipine and nitrendipine. The effect of whole body γ-radiation on the growth of the subcutaneously implanted tumors was assessed. Growth delay or regression of the tumors in mice treated with the calcium antagonists prior to irradiation was not reduced as compared to only irradiated controls. (orig.) [de

  14. Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R.; Evans, Michael J.; Lewis, Jason S.; Zanzonico, Pat; Larson, Steven M.

    2014-01-01

    The PET tracer, 124 I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal 89 Zr, however, may offer advantages as a surrogate PET nuclide over 124 I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between 124 I-cG250 and 89 Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with 89 Zr-cG250 and 124 I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using 89 Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10 12 molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of 124 I/ 89 Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of 89 Zr-cG250 and 124 I-cG250 provided the basis for a nonlinear immunokinetic

  15. Pairwise comparison of {sup 89}Zr- and {sup 124}I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Evans, Michael J. [Memorial Sloan-Kettering Cancer Center, Human Oncology and Pathogenesis Program, New York, NY (United States); Lewis, Jason S. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Radiochemistry and Imaging Sciences Service, New York, NY (United States); Zanzonico, Pat [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States); Memorial-Sloan Kettering Cancer Center, New York, NY (United States); Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States)

    2014-05-15

    The PET tracer, {sup 124}I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal {sup 89}Zr, however, may offer advantages as a surrogate PET nuclide over {sup 124}I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between {sup 124}I-cG250 and {sup 89}Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with {sup 89}Zr-cG250 and {sup 124}I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using {sup 89}Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10{sup 12} molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of {sup 124}I/{sup 89}Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of {sup 89}Zr-cG250 and {sup

  16. Thiazolidinediones abrogate cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Wuertz, Beverly R., E-mail: knier003@umn.edu; Darrah, Lindsay, E-mail: ldarrah@obgynmn.com; Wudel, Justin, E-mail: drwudel@drwudel.com; Ondrey, Frank G., E-mail: ondre002@umn.edu

    2017-04-15

    Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100 mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions. - Highlights: • Thiazolidinediones decreases cervical cancer proliferation. • Pioglitazone increases cervical cancer differentiation. • Pioglitazone decreases tumor growth in mice. • Pioglitazone may be a useful treatment adjunct.

  17. Get Tested for Cervical Cancer

    Science.gov (United States)

    ... Print This Topic En español Get Tested for Cervical Cancer Browse Sections The Basics Overview Cervical Cancer Cervical ... Cervical Cancer 1 of 5 sections The Basics: Cervical Cancer What is cervical cancer? Cervical cancer is cancer ...

  18. High-dose-rate intracavitary brachytherapy (HDR-IC) in treatment of cervical carcinoma: 5-year results and implication of increased low-grade rectal complication on initiation of an HDR-IC fractionation scheme

    International Nuclear Information System (INIS)

    Wang Chongjong; Wan Leung, Stephen; Chen Huichun; Sun Limin; Fang Fumin; Changchien Chanchao; Huang Engyen; Wu Jiaming; Chen Chuhnchih

    1997-01-01

    Purpose: To report the treatment results and rectal/bladder complications of cervical carcinoma radically treated with high-dose-rate intracavitary brachytherapy (HDR-IC). The current policy of using three-fraction scheme was examined. Methods and Materials: Between November 1987 and August 1990, 173 patients with cervical carcinoma were treated with curative-intent radiation therapy. Whole pelvic irradiation was administered with 10-MV X ray. Dose to the central cervix was 40-44 Gy in 20-22 fractions, following by pelvic wall boost 6-14 Gy in three to seven fractions with central shielding. 60 Co sources were used for HDR-IC, and 7.2 Gy was given to Point A for three applications, 1-2 weeks apart. Duration of follow-up was 5-7.8 years. Results: Twenty-eight patients (16%) developed central-regional recurrences. Overall 5-year actuarial pelvic control rate was 83%. By stage, 5-year actuarial pelvic control rates were 94%, 87%, and 72% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Thirty-one patients (18%) developed distant metastasis. Overall 5-year actuarial survival rate was 58%. By stage, 5-year actuarial survival rates were 79%, 59%, and 41% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Sixty-six (38%) and 19 patients (11%) developed rectal and bladder complications, respectively. For rectal complication, the overall actuarial rate was 38% at 5 years. By grade, 5-year actuarial rectal complication rates were 24%, 15%, 4%, and 3% for Grades 1-4, respectively. Overall prevalence of rectal complications was 37% and 14% at 2 and 5 years, respectively. Prevalence of low-grade rectal complication (Grades 1 and 2) was dominant at 2 years (30%), but declined to 8% at 5 years. Prevalence of high-grade, severe rectal complication (Grades 3 and 4) remained steady at 2 and 5 years (7% and 6%, respectively). Five-year actuarial bladder complication was 9%. Five-year prevalence of bladder complication was 2%. Conclusion: Using a three

  19. Multicenter Phase 2 Study of Cisplatin and 5-Fluorouracil With Concurrent Radiation Therapy as an Organ Preservation Approach in Patients With Squamous Cell Carcinoma of the Cervical Esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Kojima, Takashi [Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba (Japan); Kato, Ken [Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo (Japan); Izumi, Sachiko [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Ozawa, Taijiro [Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Aichi (Japan); Kiyota, Naomi [Department of Medical Oncology and Hematology, Kobe University Hospital, Hyogo (Japan); Katada, Chikatoshi [Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara (Japan); Tsushima, Takahiro [Department of Gastrointestinal Endoscopy and Oncology, Shizuoka Cancer Center Hospital, Shizuoka (Japan); Ito, Yoshinori [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Akimoto, Tetsuo [Department of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Hasegawa, Yasuhisa [Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Aichi (Japan); Kanamaru, Miyuki [Department of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Daiko, Hiroyuki [Department of Surgery, National Cancer Center Hospital East, Chiba (Japan)

    2016-12-01

    Purpose: To clarify, in a multicenter, single-arm, phase 2 study (UMIN Clinical Trials Registry no. UMIN000001439), the clinical profile of chemoradiotherapy (CRT) for cervical esophageal cancer. Patients and Methods: Patients with operable cervical esophageal cancer, excluding candidates for endoscopic resection, were enrolled. Protocol treatment consisted of CRT and adjuvant chemotherapy (CT). First, patients received concurrent CRT with 5-fluorouracil (5-FU) plus cisplatin (CDDP). Chemotherapy consisted of 5-FU at 700 mg/m{sup 2} intravenous on days 1 to 4 and CDDP at 70 mg/m{sup 2} intravenous on day 1, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 60 Gy in 30 fractions. After completion of CRT, 2 additional cycles of CT with 5-FU (800 mg/m{sup 2}, days 1-5) and CDDP (80 mg/m{sup 2}, day 1) were repeated at a 4-week interval. The primary endpoint was 3-year overall survival. Results: Thirty patients were enrolled across 8 institutions in Japan, consisting of 26 men and 4 women with a median age of 64.5 years (range, 50-75 years). No grade 4 hematologic toxicity was seen in the CRT phase, and 1 grade 4 thrombocytopenia was seen in the CT phase. Grade 3 nonhematologic acute toxicities in the CRT phase were nausea (10%), mucositis (13.3%), and dysphagia (13.3%). No treatment-related death in either phase occurred. Overall complete response rate was 73%, and 3-year overall and laryngectomy-free survival were 66.5% and 52.5%, respectively. Regarding T4 disease, 3-year overall and laryngectomy-free survival were 58.3% and 38.5%, respectively. Conclusions: This study, the first prospective study for cervical esophageal cancer, showed that CRT has sufficient efficacy and safety for use as an alternative to surgery for these patients.

  20. Detection of angiogenesis-dependent parameters by functional MRI: Correlation between histomorphology and evaluation of clinical relevance as prognostic factor for the example of cervical carcinoma

    International Nuclear Information System (INIS)

    Hawighorst, H.; Knopp, M.V.; Schoenberg, S.O.; Essig, M.; Kaick, G. van; Schaeffer, U.; Knapstein, P.G.; Weikel, W.

    1998-01-01

    Purpose: Purpose of this study is to compare functional MRI parameters with histomorphological markers of tumor microvessel density (MVD) and permeability (vascular endothelial growth factor) and to determine the ultimate value of both approaches by correlation with disease outcome in patients with primary cancer of the uterine cervix. Method: Pharmacokinetic parameters were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the operative whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using logrank statistics. Results: Significant (p [de

  1. Vitrification and xenografting of human ovarian tissue.

    Science.gov (United States)

    Amorim, Christiani Andrade; Dolmans, Marie-Madeleine; David, Anu; Jaeger, Jonathan; Vanacker, Julie; Camboni, Alessandra; Donnez, Jacques; Van Langendonckt, Anne

    2012-11-01

    To assess the efficiency of two vitrification protocols to cryopreserve human preantral follicles with the use of a xenografting model. Pilot study. Gynecology research unit in a university hospital. Ovarian biopsies were obtained from seven women aged 30-41 years. Ovarian tissue fragments were subjected to one of three cryopreservation protocols (slow freezing, vitrification protocol 1, and vitrification protocol 2) and xenografted for 1 week to nude mice. The number of morphologically normal follicles after cryopreservation and grafting and fibrotic surface area were determined by histologic analysis. Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL-positive surface area also was performed. Follicle proliferation was evaluated by immunohistochemistry. After xenografting, a difference was observed between the cryopreservation procedures applied. According to TUNEL analysis, both vitrification protocols showed better preservation of preantral follicles than the conventional freezing method. Moreover, histologic evaluation showed a significantly higher proportion of primordial follicles in vitrified (protocol 2)-warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing follicles and fibrotic surface area was similar in all groups. Vitrification procedures appeared to preserve not only the morphology and survival of preantral follicles after 1 week of xenografting, but also their ability to resume folliculogenesis. In addition, vitrification protocol 2 had a positive impact on the quiescent state of primordial follicles after xenografting. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Knowledge, Attitude and Practice of Cervical Smear as a Screening ...

    African Journals Online (AJOL)

    Context: Carcinoma of the cervix is a preventable disease but it remains the most common genital cancer in African women. Objective: To determine the knowledge, attitude and practice of cervical smear as screening procedure for cervical cancer by female health workers in Ilorin, Nigeria. Study Design, Setting and ...

  3. [Cervical cerclage].

    Science.gov (United States)

    Akladios, C Y; Sananes, N; Gaudineau, A; Boudier, E; Langer, B

    2015-10-01

    Cervical cerclage aims to strengthen not only the mechanical properties of the cervix, but also its immunological and anti-infectious functions. The demonstration of a strong interrelation between cervical insufficiency as well as decreased cervical length at endo-vaginal ultrasonography and infection has changed the indications cerclage. Actually we can distinguish three indications for cerclage: prophylactic, for obstetrical history; therapeutic, for shortened cervical length at ultrasonography in patients at risk and; emergency cerclage in case of threatening cervix at physical examination. The McDonald's technique is the most recommended. In case of failure, it is proposed to realize cerclage at a higher level on the cervix either by vaginal or abdominal route. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Cervical Cancer

    Science.gov (United States)

    ... I find more information about cervical and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...

  5. Cervical Laminoplasty

    Science.gov (United States)

    ... Nerve Tests: EMG, NCV and SEEP Alternative Medicine Acupuncture Herbal Supplements Surgical Options Anterior Cervical Fusion Artifical ... tasks. A NASS physician can perform a thorough history to evaluate your symptoms and any recent changes. ...

  6. Cervical spondylosis

    Science.gov (United States)

    Cervical osteoarthritis; Arthritis - neck; Neck arthritis; Chronic neck pain; Degenerative disk disease ... therapist). Sometimes, a few visits will help with neck pain. Cold packs and heat therapy may help your ...

  7. Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Partha, E-mail: BasuP@iarc.fr [Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon (France); Jenson, Alfred Bennett [James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky (United States); Majhi, Tapas; Choudhury, Prabir [Department of Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Mandal, Ranajit; Banerjee, Dipanwita [Department of Gynecological Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Biswas, Jaydip [Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Pan, Jianmin; Rai, Shesh Nath; Ghim, Shin je; Miller, Donald [James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky (United States)

    2016-01-01

    Purpose: Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer. Methods and Materials: Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10{sup 6} IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m{sup 2}) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years. Results: Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy–related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths. Conclusions: Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The

  8. Hypothyroidism following cervical irradiation in the management of carcinoma of the nasopharynx and of the breast: a prospective study on eighty-four cases

    International Nuclear Information System (INIS)

    Daoud, J.; Siala, W.; Guermazi, F.; Besbes, M.; Frikha, M.; Ghorbel, M.; Drira, M.; Abid, M.

    2005-01-01

    Purpose. - 1/ To evaluate the incidence of hypothyroidism following radiotherapy in the management of breast and nasopharyngeal carcinomas, 2/ to define the role of a systematic post therapeutic screening. Patients and methods. - From January 1996 through March 2001 a systematic evaluation of the clinical and the biological thyroid function was performed on a cohort of 84 patients that received supraclavicular irradiation. Selected patients had either a mammary (37 cases) or a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid inspection and palpation, and biological tests: serum FT4 and TSH levels, radio-immuno-chemistry, completed by dynamic thyroid stimulation, using TRH, in case of border line low T4 or isolated high TSH levels. Tests were repeated every three months the first year, and then every six months. Replacement therapy with L Thyroxine was administered in case of hypothyroidism. Results. - All selected patients had a normal function initially. With a mean two years follow up (1-5 years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases) being purely biological. Five patients (11%), with a nasopharyngeal carcinoma, presented also with associated pituitary failure. Clinical symptoms were minor or mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In 2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible predictive factors were evaluated: age of the time of radiation, gender, percentage of irradiated thyroid, total dose, dose per fraction, tumour type and chemotherapy. Only age appeared significantly correlated with thyroid dysfunction (range: 10-30 years, P = 0.002). Conclusion. - Hypothyroidism is a frequent and certainly underestimated complication following radiotherapy of the neck. In such patients, a systematic clinical and biological evaluation every three months the first year, and then every six months until five years is recommended. (authors)

  9. Concomitant chemo radiation in the treatment of advanced cervical carcinoma; Radiotherapie et chimiotherapie concomitante dans le traitement des cancers avances du col uterin

    Energy Technology Data Exchange (ETDEWEB)

    Resbeut, M. [Institut Paoli-Calmettes, 13 - Marseille (France); Hennequin, C. [Hopital Saint-Louis, 75 - Paris (France)

    1994-12-31

    The study results of non randomized radio chemotherapy in the cervix cancer treatment are cheering and clinically the answers are faster. However only some randomized studies using hydroxyurea showed a benefit in survival term. The association tolerance of 5 FU with cisplatin is generally acceptable but we don`t know yet the long-range toxicity. Finally we`ll have to determine in which quantity, the pelvis control improvement should be able to increase the survival rate, because the metastases are frequent in these